JP2007538047A - 7-substituted benzimidazoles and their use as inhibitors of gastric acid secretion - Google Patents

Abstract

  The present invention provides a compound represented by the formula (1), the substituents and symbols of which are as defined in the specification. The compound inhibits gastric acid secretion.

Description

  The present invention relates to novel compounds used in the pharmaceutical industry as active compounds for the manufacture of pharmaceuticals.

BACKGROUND ART European patent application EP0266326 (corresponding to US Pat. No. 5,106,862) discloses benzimidazole derivatives having a wide variety of substituents, which are effective as antiulcer agents. It is said. International patent application WO 97/47603 (which corresponds to US Pat. No. 6,465,505) discloses benzimidazole derivatives with very specialized substitutions, which are known for gastric acid secretion. Therefore, it can be used for the prevention and treatment of gastrointestinal inflammatory diseases.

  Torigoe et al., In Phytocchemistry, 1972, 11, 1623, describe the cytokine activity of derivatives of azaindene, azanaphthalene, naphthalene and indole in tobacco pulp callus bioassay.

  Dincer et al., In Indian Journal of Chemistry, Section B, 1995, 34 (11), 982, describe the synthesis of 4- (substituted benzylamino) benzimidazole derivatives, whose structure and cytokine activity. Insight into the correlation between is expected.

  US Pat. No. 6,083,961 describes benzimidazole compounds having activity as bradykinin antagonists, such as allergies, inflammation, autoimmune diseases, shock, pain, etc. It is said to be useful for treatment.

  Brauninger et al., In Archiv der Pharmazie, 1966, 299 (3), describe the synthesis of some benzimidazole derivatives and their kinetin activity.

  International Patent Application WO 04/054984 discloses benzimidazole derivatives having a wide variety of substituents substituted at the 4-position, and the compounds are useful for the suppression and treatment of gastrointestinal diseases.

  International patent application WO 94/18199 (corresponding to US Pat. No. 5,665,730) discloses imidazopyridine derivatives and their use in the treatment of gastrointestinal diseases.

DISCLOSURE OF THE INVENTION Technical Problem The entire series of compounds that inhibit gastric acid secretion by blocking H ⁺ / K ⁺ -ATPase are known from the prior art. Compounds termed proton pump inhibitors (PPI), such as omeprazole, esomeprazole, lansoprazole, pantoprazole or rabeprazole, bind irreversibly to H ⁺ / K ⁺ -ATPase. PPI has already been used as a therapeutic agent for a long time. A new class of compounds called reversible proton pump inhibitors (rPPI) or acid pump antagonists (APA) binds reversibly to H ⁺ / K ⁺ -ATPases. rPPI or APA has been known for over 20 years and many companies have been involved in its development, but no rPPI or APA is currently used for treatment. Therefore, the technical problem underlying the present invention is to provide an acid pump antagonist that can be used in therapy.

Technical Solution

［式中、
Ｒ１は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_３〜Ｃ_７−シクロアルキル、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル、Ｃ_２〜Ｃ_４−アルケニル、Ｃ_２〜Ｃ_４−アルキニル、フルオロ−Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ又はＣ_１〜Ｃ_４−アルキルカルボニルオキシ−Ｃ_１〜Ｃ_４−アルキルであり、
Ｒ２は、水素、Ｃ_１〜Ｃ_４−アルキル、アリール、Ｃ_３〜Ｃ_７−シクロアルキル、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、フルオロ−Ｃ_２〜Ｃ_４−アルキル、アリール−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ又はＣ_１〜Ｃ_４−アルコキシであり、
Ｒ３は、水素、ハロゲン、フルオロ−Ｃ_１〜Ｃ_４−アルキル、カルボキシル、−ＣＯ−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、シアノ、基−ＣＯ−ＮＲ３１Ｒ３２、基ＳＯ_２−ＮＲ３１Ｒ３２又は基Ｈｅｔであり、その際、
Ｒ３１は、水素、ヒドロキシル、Ｃ_１〜Ｃ_７−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル又はＣ_３〜Ｃ_７−シクロアルキル、アミノであり、かつ
Ｒ３２は、水素、Ｃ_１〜Ｃ_７−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルであるか、又は
Ｒ３１及びＲ３２は、一緒になって、その両者が結合される窒素原子を含んで、ピロリジノ基、ピペリジノ基、ピペラジノ基、Ｎ−Ｃ_１〜Ｃ_４−アルキルピペラジノ基、モルホリノ基、アジリジノ基又はアゼチジノ基であり、かつ
Ｈｅｔは、Ｒ３３、Ｒ３４及びＲ３５により置換された、オキサジアゾール、ジヒドロオキサゾール、ジヒドロイミダゾール、オキサゾール、イミダゾール、イソキサゾール、ジヒドロイソキサゾール、ピラゾール及びテトラゾールからなる群から選択される複素環基であり、その際、
Ｒ３３は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_２〜Ｃ_４−アルケニルオキシ、Ｃ_１〜Ｃ_４−アルキルカルボニル、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、カルボキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル−Ｃ_１〜Ｃ_４−アルキル、ハロゲン、ヒドロキシ、アリール、アリール−Ｃ_１〜Ｃ_４−アルキル、アリールオキシ、アリール−Ｃ_１〜Ｃ_４−アルコキシ、トリフルオロメチル、ニトロ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はスルホニルであり、
Ｒ３４は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｒ３５は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｘは、Ｏ（酸素）又はＮＨであり、かつ
Ｙは、−ＣＨ_２−Ａｒの意味を有し、その際、
Ａｒは、Ｒ４、Ｒ５、Ｒ６及びＲ７により置換された、フェニル、ナフチル、ピロリル、ピラゾリル、イミダゾリル、１，２，３−トリアゾリル、インドリル、ベンゾイミダゾリル、フリル、ベンゾフリル、チエニル、ベンゾチエニル、チアゾリル、イソキサゾリル、ピリジニル、ピリミジニル、キノリニル及びイソキノリニルからなる群から選択される、単環式もしくは二環式の芳香族基であるか、又は
Ｙは、基ｇｐ

[Where:
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH and Y has the meaning —CH ₂ —Ar, where
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6 and R7 Is a monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl, or Y is a group gp

を示し、その際、
Ｚは、−ＣＨＲ８−又は−ＣＨＲ８−ＣＨＲ９−を意味し、その際、
Ａｒ及び／又は基ｇｐにおいて、
Ｒ４は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_２〜Ｃ_４−アルケニルオキシ、Ｃ_１〜Ｃ_４−アルキルカルボニル、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、カルボキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル−Ｃ_１〜Ｃ_４−アルキル、ハロゲン、ヒドロキシ、アリール、アリール−Ｃ_１〜Ｃ_４−アルキル、アリールオキシ、アリール−Ｃ_１〜Ｃ_４−アルコキシ、トリフルオロメチル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ、ニトロ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はスルホニルであり、
Ｒ５は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｒ６は、水素、Ｃ_１〜Ｃ_４−アルキル又はハロゲンであり、かつ
Ｒ７は、水素、Ｃ_１〜Ｃ_４−アルキル又はハロゲンであり、
Ｒ８は、水素、Ｃ_１〜Ｃ_７−アルキル、Ｃ_２〜Ｃ_７−アルケニル、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、
Ｒ９は、水素、Ｃ_１〜Ｃ_７−アルキル、Ｃ_２〜Ｃ_７−アルケニル、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、かつ
アリールは、フェニル又は、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル、ニトロ、トリフルオロメトキシ、ヒドロキシ及びシアノの群からの１個、２個又は３個の同一又は異なる置換基で置換されたフェニルである］で示される化合物及びこれらの化合物の塩に関する。

In doing so,
Z means —CHR8— or —CHR8—CHR9—,
In Ar and / or the group gp,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
R8 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
R9 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy and aryl is phenyl _or, C 1 -C ₄ - 1, 2 or 3 identical from the group of alkyl, C ₁ -C ₄ -alkoxy, carboxy, C ₁ -C ₄ -alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and cyano Or phenyl substituted with a different substituent] and salts of these compounds Related.

C ₁ -C ₄ -alkyl represents a linear or branched alkyl group having 1 to 4 carbon atoms. Examples which may be mentioned are butyl, isobutyl, s-butyl, t-butyl, propyl, isopropyl, ethyl and methyl.

C 3 _-C 7 _- cycloalkyl represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, of which cyclopropyl, cyclobutyl and cyclopentyl advantageous.

C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl is one of said C ₁ -C ₄ -alkyl groups substituted by one of said C ₃ -C ₇ -cycloalkyl groups Represents. Examples which may be mentioned are the cyclopropylmethyl group, the cyclohexylmethyl group and the cyclohexylethyl group.

C ₁ -C ₄ -alkoxy represents a group having a linear or branched alkyl group having 1 to 4 carbon atoms in addition to an oxygen atom. Examples which may be mentioned are butoxy, isobutoxy, s-butoxy, t-butoxy, propoxy, isopropoxy and preferably ethoxy and methoxy groups.

C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl represents one of the aforementioned C ₁ -C ₄ -alkyl groups substituted by one of the aforementioned C ₁ -C ₄ -alkoxy groups. Examples which may be mentioned are methoxymethyl, methoxyethyl and butoxyethyl groups.

C ₁ -C ₄ -alkoxycarbonyl (—CO—C ₁ -C ₄ -alkoxy) represents a carbonyl group to which one of the aforementioned C ₁ -C ₄ -alkoxy groups is bonded. Examples which may be mentioned are the methoxycarbonyl (CH ₃ O—C (O) —) and ethoxycarbonyl (CH ₃ CH ₂ O—C (O) —) groups.

C 2 _-C 4 _- alkenyl represents a straight-chain or branched alkenyl group having 2 to 4 carbon atoms. Examples which may be mentioned are 2-butenyl, 3-butenyl, 1-propenyl and 2-propenyl (allyl).

C 2 _-C 4 _- Alkynyl denotes straight-chain or branched alkynyl group having 2 to 4 carbon atoms. Examples which may be mentioned are 2-butynyl, 3-butynyl, and preferably 2-propynyl (propargyl).

Fluoro _-C 1 -C ₄ - alkyl, said which is substituted by one or more fluorine atoms _C 1 -C ₄ - represents one of the alkyl groups. An example which may be mentioned is the trifluoromethyl group.

Hydroxy-C ₁ -C ₄ -alkyl represents the aforementioned C ₁ -C ₄ -alkyl group substituted with a hydroxyl group. Examples which may be mentioned are hydroxymethyl, 2-hydroxyethyl and 3-hydroxypropyl.

C ₁ -C ₄ -alkylcarbonyl represents a group having one of the aforementioned C ₁ -C ₄ -alkyl groups in addition to the carbonyl group. An example which may be mentioned is the acetyl group.

Mono- or di-C ₁ -C ₄ -alkylamino represents an amino group which is substituted from the above C ₁ -C ₄ -alkyl group or by two identical or different groups. Examples which may be mentioned are the dimethylamino group, the diethylamino group and the diisopropylamino group.

Mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, one mono- - or di _{-C 1 ~C 4 - C 1 ~C} 4 which is substituted by an alkyl amino group - Represents an alkylcarbonyl group. Examples which may be mentioned are the dimethylaminomethylcarbonyl group and the dimethylaminoethylcarbonyl group.

Fluoro _-C 2 -C ₄ - alkyl, one or more of one which is substituted by fluorine atom _C 2 -C ₄ - alkyl group. An example which may be mentioned is the 2,2,2-trifluoroethyl group.

Aryl-C ₁ -C ₄ -alkoxy represents an aryl-substituted C ₁ -C ₄ -alkoxy group. An example which may be mentioned is the benzyloxy group.

Aryl-C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl is one of the aforementioned C ₁ -C ₄ -alkyl groups, which is the aforementioned aryl-C ₁ -C ₄ -alkoxy group Represents a group substituted by one of An example which may be mentioned is the benzyloxymethyl group.

  Halogen is bromine, chlorine and fluorine within the meaning of the invention.

C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy, the other _C 1 -C ₄ - of the which is substituted by an alkoxy group _C 1 -C ₄ - represents one of the alkoxy groups. Examples that may be mentioned are 2- (methoxy) ethoxy (CH ₃ —O—CH ₂ —CH ₂ —O—) and 2- (ethoxy) ethoxy (CH ₃ —CH ₂ —O—CH ₂ —CH ₂ —O—). ) Group.

C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, _C 1 of the -C ₄ - above which is substituted by one alkoxy group _C 1 -C ₄ - represents one of alkyl group - alkoxy _-C 1 -C _4. An example which may be mentioned is the 2- (methoxy) ethoxymethyl (CH ₃ —O—CH ₂ —CH ₂ —O—CH ₂ —) group.

Fluoro-C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl represents one of the aforementioned C ₁ -C ₄ -alkyl groups substituted by a fluoro-C ₁ -C ₄ -alkoxy group. In this case, fluoro-C ₁ -C ₄ -alkoxy represents one of the aforementioned C ₁ -C ₄ -alkoxy groups, this group being completely or mainly substituted by fluorine. Examples of C ₁ -C ₄ -alkoxy groups which are completely or predominantly substituted with fluorine are 1,1,1,3,3,3-hexafluoro-2-propoxy group, 2-trifluoromethyl- 2-propoxy group, 1,1,1-trifluoro-2-propoxy group, perfluoro-t-butoxy group, 2,2,3,3,4,4,4-heptafluoro-1-butoxy group, 4, 4,4-trifluoro-1-butoxy group, 2,2,3,3,3-pentafluoropropoxy group, perfluoroethoxy group or 1,2,2-trifluoroethoxy group, especially 1,1,2 , 2-tetrafluoroethoxy group, 2,2,2-trifluoroethoxy group, trifluoromethoxy group and preferably difluoromethoxy group. Examples of fluoro-C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl groups that may be mentioned include 1,1,2,2-tetrafluoroethoxymethyl group, 2,2,2-trifluoroethoxymethyl group, Trifluoromethoxymethyl group, 1,1,2,2-tetrafluoroethoxyethyl group, 2,2,2-trifluoroethoxyethyl group, trifluoromethoxyethyl group, preferably difluoromethoxymethyl group and difluoromethoxy An ethyl group.

C ₁ -C ₇ -alkyl represents a linear or branched alkyl group having 1 to 7 carbon atoms. Examples include heptyl group, isoheptyl (5-methylhexyl) group, hexyl group, isohexyl (4-methylpentyl) group, neohexyl (3,3-dimethylbutyl) group, pentyl group, isopentyl (3-methylbutyl) group. , Neopentyl (2,2-dimethylpropyl) group, butyl group, isobutyl group, s-butyl group, t-butyl group, propyl group, isopropyl group, ethyl group and methyl group.

C ₂ -C ₄ - alkenyloxy, _C 2 -C ₄ in addition to said oxygen atom - group having one alkenyl group. Examples which may be mentioned are 2-butenyloxy, 3-butenyloxy, 1-propenyloxy and 2-propenyloxy (allyloxy).

Carboxy-C ₁ -C ₄ -alkyl represents a C ₁ -C ₄ -alkyl group substituted by a carboxyl group. Examples which may be mentioned are the carboxymethyl group and the 2-carboxyethyl group.

C ₁ -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, _C 1 -C ₄ said - represents an alkyl group - _C 1 -C ₄ substituted by one alkoxycarbonyl group. Examples which may be mentioned are the methoxycarbonylmethyl group and the ethoxycarbonylmethyl group.

Aryl-C ₁ -C ₄ -alkyl represents an aryl-substituted C ₁ -C ₄ -alkyl group. An example which may be mentioned is the benzyl group.

C ₁ -C ₄ -alkylcarbonylamino represents an amino group to which a C ₁ -C ₄ -alkylcarbonyl group is bonded. Examples which may be mentioned are the propionylamino radical _{(C 3 H 7 C (O} ) NH-) and acetyl amino group (acetamido _{group) (CH 3 C (O)} NH-).

C ₁ -C ₄ - alkoxycarbonylamino is, _C 1 -C ₄ above - an amino group which is substituted by one alkoxycarbonyl group. Examples which may be mentioned are the ethoxycarbonylamino group and the methoxycarbonylamino group.

C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkoxycarbonyl represents a carbonyl group that is bonded to one of the aforementioned C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkoxy groups. Examples that may be mentioned are 2- (methoxy) ethoxycarbonyl (CH ₃ —O—CH ₂ CH ₂ —O—CO—) and 2- (ethoxy) ethoxycarbonyl (CH ₃ CH ₂ —O—CH ₂ CH ₂ —O). -CO-) group.

C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino is, _C 1 -C ₄ above - an amino group which is substituted by one alkoxycarbonyl group - alkoxy _-C 1 -C _4. Examples which may be mentioned are 2- (methoxy) ethoxycarbonylamino group and 2- (ethoxy) ethoxycarbonylamino group.

C 2 _-C 7 _- alkenyl represents a straight-chain or branched alkenyl group having 2 to 7 carbon atoms. Examples which may be mentioned are 2-butenyl, 3-butenyl, 1-propenyl and 2-propenyl (allyl) and vinyl. The above C ₂ -C ₄ -alkenyl groups are preferred.

C 2 _-C 7 _- alkenyl represents a straight-chain or branched alkenyl group having 2 to 7 carbon atoms. Examples which may be mentioned are 2-butenyl, 3-butenyl, 1-propenyl and 2-propenyl (allyl) and vinyl. The above C ₂ -C ₄ -alkenyl groups are preferred.

Oxo-substituted _C 1 -C ₄ - alkoxy, _C 1 -C ₄ having a place of the carbonyl group of the methylene group - represents an alkoxy group. An example which may be mentioned is the 2-oxopropoxy group.

C 3 _-C 7 _- cycloalkoxy represents cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy and cycloheptyloxy, of which cyclopropyloxy, is cyclobutyloxy and cyclopentyloxy advantageous.

C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkoxy is one of said C ₁ -C ₄ -alkoxy groups substituted by one of said C ₃ -C ₇ -cycloalkyl groups Represents. Examples which may be mentioned are cyclopropylmethoxy, cyclobutylmethoxy and cyclohexylethoxy groups.

Hydroxy-C ₁ -C ₄ -alkoxy represents the aforementioned C ₁ -C ₄ -alkoxy group substituted with a hydroxyl group. An advantageous example which may be mentioned is the 2-hydroxyethoxy group.

C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy, wherein the _C 1 -C ₄ - which is substituted by one alkoxy group - alkoxy _-C 1 -C ₄ wherein the _C 1 -C ₄ - represents one of the alkoxy groups. An advantageous example which may be mentioned is the methoxyethoxyethoxy group.

C ₃ -C ₇ -cycloalkoxy-C ₁ -C ₄ -alkoxy is one of said C ₁ -C ₄ -alkoxy groups substituted by one of said C ₃ -C ₇ -cycloalkoxy groups Represents. Examples which may be mentioned are the cyclopropoxymethoxy group, the cyclobutoxymethoxy group and the cyclohexyloxyethoxy group.

C ₃ -C ₇ - cycloalkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy, wherein the _C 3 -C ₇ - substituted by one alkoxy group - cycloalkyl _-C 1 -C ₄ Represents one of the aforementioned C ₁ -C ₄ -alkoxy groups. Examples which may be mentioned are the cyclopropylmethoxyethoxy group, the cyclobutylmethoxyethoxy group and the cyclohexylethoxyethoxy group.

C ₁ -C ₄ -alkylcarbonyloxy represents a C ₁ -C ₄ -alkylcarbonyl group bonded to an oxygen atom. An example which may be mentioned is the acetoxy group (CH ₃ CO—O—).

C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl is one of said C ₁ -C ₄ -alkyl groups substituted by one of said C ₁ -C ₄ -alkylcarbonyloxy groups. Represents one. Examples which may be mentioned is the acetoxymethyl group _{(CH 3 CO-O-CH} 2).

Halogen-C ₁ -C ₄ -alkoxy represents a C ₁ -C ₄ -alkoxy group which is completely or mainly substituted by halogen. In the present specification, “mainly” means that more than half of the hydrogen atoms in the C ₁ -C ₄ -alkoxy group are substituted with halogen atoms. A halogen-C ₁ -C ₄ -alkoxy group is primarily a C ₁ -C ₄ -alkoxy group which is chlorine and / or especially fluorine-substituted. Examples of halogen-substituted C ₁ -C ₄ -alkoxy groups are 2,2,2-trichloroethoxy group, hexachloroisopropoxy group, pentachloroisopropoxy group, 1,1,1-trichloro-3,3 , 3-trifluoro-2-propoxy group, 1,1,1-trichloro-2-methyl-2-propoxy group, 1,1,1-trichloro-2-propoxy group, 3-bromo-1,1,1 -Trifluoro-2-propoxy group, 3-bromo-1,1,1-trifluoro-2-butoxy group, 4-bromo-3,3,4,4-tetrafluoro-1-butoxy group, chlorodifluoromethoxy Group, 1,1,1,3,3,3-hexafluoro-2-propoxy group, 2-trifluoromethyl-2-propoxy group, 1,1,1-trifluoro-2-propoxy group, per Fluoro-t-butoxy group, 2,2,3,3,4,4,4-heptafluoro-1-butoxy group, 4,4,4-trifluoro-1-butoxy group, 2,2,3,3 , 3-pentafluoropropoxy group, perfluoroethoxy group, 1,2,2-trifluoroethoxy group, especially 1,1,2,2-tetrafluoroethoxy group, 2,2,2-trifluoroethoxy group, trifluoro A methoxy group and preferably a difluoromethoxy group.

Mono- or di-C ₁ -C ₄ -alkylamino-C ₁ -C ₄ -alkylcarbonyloxy is C ₁ substituted by one of the above mono- or di-C ₁ -C ₄ -alkylamino groups. It represents an alkylcarbonyloxy group - -C _4. Examples which may be mentioned are the dimethylaminomethylcarbonyloxy group and the dimethylaminoethylcarbonyloxy group.

C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkylcarbonyloxy is a group of said C ₁ -C ₄ -alkylcarbonyloxy group substituted by one of said C ₁ -C ₄ -alkoxy groups. Represents one. An example which may be mentioned is the methoxymethylcarbonyloxy group.

  In this respect, suitable salts of the compounds of the formula 1 are in particular all acid addition salts, depending on the substitution. Particular mention may be made of pharmacologically acceptable salts of inorganic and organic acids conventionally used in pharmacy. Preferably they are acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) benzoic acid, butyric acid, sulfo Water-soluble or non-soluble with salicylic acid, maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid A water-soluble acid addition salt, which depends on whether the acid is a monobasic acid or a polybasic acid, and depending on which salt is desired, the preparation of the salt In an equimolar ratio or a different ratio.

  During the production of the compounds according to the invention on an industrial scale, for example, pharmacologically unacceptable salts which can be obtained initially as process products are pharmacologically acceptable salts by methods known to those skilled in the art. Is converted to

  It is known to the person skilled in the art that the compounds according to the invention and their salts may have various amounts of solvent, for example when they are isolated in crystalline form. The invention therefore also includes all solvates and especially all hydrates of the compounds of the formula 1, and all solvates and especially all hydrates of the salts of the compounds of the formula 1.

One embodiment (embodiment 1) of the present invention is represented by formula 1, wherein:
X is O (oxygen),
R1, R2, R3 and Y relate to compounds having the meanings indicated at the outset and salts of these compounds.

Another embodiment of the present invention (embodiment 2) is represented by formula 1, wherein
X is NH,
R1, R2, R3 and Y relate to compounds having the meanings indicated at the outset and salts of these compounds.

Another embodiment of the present invention (embodiment 3) is represented by formula 1, wherein:
X is hydrogen,
R1, R2, R3 and Y relate to compounds having the meanings indicated at the outset and salts of these compounds.

Yet another embodiment of the present invention (embodiment 4) is represented by formula 1, wherein:
R3 does not mean hydrogen,
R1, R2, X and Y relate to compounds having the meanings indicated at the outset and salts of these compounds.

Yet another embodiment of the present invention (Embodiment 5) is shown in Formula 1, wherein:
R3 is halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group - CO—NR31R32, the group SO ₂ —NR31R32 or the group Het,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R1, R2, X and Y relate to compounds having the meanings indicated at the outset and salts of these compounds.

The present invention is also represented by Formula 1, wherein
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH and Y has the meaning —CH ₂ —Ar, where
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 Is a monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl, or Y is a group gp

を示し、その際、
Ｚは、−ＣＨＲ８−又は−ＣＨＲ８−ＣＨＲ９−を意味し、その際、
Ａｒ及び／又は基ｇｐにおいて、
Ｒ４は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_２〜Ｃ_４−アルケニルオキシ、Ｃ_１〜Ｃ_４−アルキルカルボニル、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、カルボキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル−Ｃ_１〜Ｃ_４−アルキル、ハロゲン、ヒドロキシ、アリール、アリール−Ｃ_１〜Ｃ_４−アルキル、アリールオキシ、アリール−Ｃ_１〜Ｃ_４−アルコキシ、トリフルオロメチル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ、ニトロ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はスルホニルであり、
Ｒ５は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｒ６は、水素、Ｃ_１〜Ｃ_４−アルキル又はハロゲンであり、かつ
Ｒ７は、水素、Ｃ_１〜Ｃ_４−アルキル又はハロゲンであり、
Ｒ８は、水素、Ｃ_１〜Ｃ_７−アルキル、Ｃ_２〜Ｃ_７−アルケニル、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、
Ｒ９は、水素、Ｃ_１〜Ｃ_７−アルキル、Ｃ_２〜Ｃ_７−アルケニル、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、かつ
アリールは、フェニル又は、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル、ニトロ、トリフルオロメトキシ、ヒドロキシ及びシアノの群からの１個、２個又は３個の同一又は異なる置換基で置換されたフェニルであるが、但し、
Ｒ３は、Ｒ１及びＲ２が水素又はＣ_１〜Ｃ_４−アルキルを意味し、かつＹがＣＨ_２−フェニル又はＣ_１〜Ｃ_４−アルコキシ基により置換されたＣＨ_２−フェニルを示す場合に、水素を意味しない化合物及びこれらの化合物の塩に関する。

In doing so,
Z means —CHR8— or —CHR8—CHR9—,
In Ar and / or the group gp,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
R8 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
R9 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy and aryl is phenyl _or, C 1 -C ₄ - 1, 2 or 3 identical from the group of alkyl, C ₁ -C ₄ -alkoxy, carboxy, C ₁ -C ₄ -alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and cyano Or phenyl substituted with different substituents, provided that
R3 is, R1 and R2 are hydrogen or a _C 1 _{~C 4} - CH ₂ substituted by an alkoxy group - - means an alkyl, and Y is CH ₂ - phenyl or _C 1 -C ₄ when a phenyl, hydrogen And the salts of these compounds.

The present invention is also represented by Formula 1, wherein
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH and Y has the meaning —CH ₂ —Ar, where
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 Is a monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl, or Y is a group gp

を示し、その際、
Ｚは、−ＣＨＲ８−又は−ＣＨＲ８−ＣＨＲ９−を意味し、その際、
Ａｒ及び／又は基ｇｐにおいて、
Ｒ４は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_２〜Ｃ_４−アルケニルオキシ、Ｃ_１〜Ｃ_４−アルキルカルボニル、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、カルボキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル−Ｃ_１〜Ｃ_４−アルキル、ハロゲン、ヒドロキシ、アリール、アリール−Ｃ_１〜Ｃ_４−アルキル、アリールオキシ、アリール−Ｃ_１〜Ｃ_４−アルコキシ、トリフルオロメチル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ、ニトロ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はスルホニルであり、
Ｒ５は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｒ６は、水素、Ｃ_１〜Ｃ_４−アルキル又はハロゲンであり、かつ
Ｒ７は、水素、Ｃ_１〜Ｃ_４−アルキル又はハロゲンであり、
Ｒ８は、水素、Ｃ_１〜Ｃ_７−アルキル、Ｃ_２〜Ｃ_７−アルケニル、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、
Ｒ９は、水素、Ｃ_１〜Ｃ_７−アルキル、Ｃ_２〜Ｃ_７−アルケニル、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、かつ
アリールは、フェニル又は、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル、ニトロ、トリフルオロメトキシ、ヒドロキシ及びシアノの群からの１個、２個又は３個の同一又は異なる置換基で置換されたフェニルであるが、但し、
Ｒ３は、Ｒ１が水素、Ｃ_１〜Ｃ_４−アルキル又はヒドロキシ−Ｃ_１〜Ｃ_４−アルキルを示し、Ｒ２が水素、Ｃ_１〜Ｃ_４−アルキル又はＣ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルキルを示し、かつＹがＣＨ_２−Ａｒを示す場合に、水素又はハロゲンを意味しない化合物及びこれらの化合物の塩に関する。

In doing so,
Z means —CHR8— or —CHR8—CHR9—,
In Ar and / or the group gp,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
R8 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
R9 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy and aryl is phenyl _or, C 1 -C ₄ - 1, 2 or 3 identical from the group of alkyl, C ₁ -C ₄ -alkoxy, carboxy, C ₁ -C ₄ -alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and cyano Or phenyl substituted with different substituents, provided that
R3 is, R1 is _hydrogen, C 1 ~C ₄ - alkyl or hydroxy _-C 1 -C ₄ - represents an alkyl, R2 is _hydrogen, C 1 ~C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl -C ₁ -C 4 _- represents an alkyl, and when Y represents a CH 2 _-Ar, a compound does not mean a hydrogen or halogen and a salt of these compounds.

  In one aspect, the present invention provides compounds of formula 1a

［式中、
Ｒ１は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_３〜Ｃ_７−シクロアルキル、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル、Ｃ_２〜Ｃ_４−アルケニル、Ｃ_２〜Ｃ_４−アルキニル、フルオロ−Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ又はＣ_１〜Ｃ_４−アルキルカルボニルオキシ−Ｃ_１〜Ｃ_４−アルキルであり、
Ｒ２は、水素、Ｃ_１〜Ｃ_４−アルキル、アリール、Ｃ_３〜Ｃ_７−シクロアルキル、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、フルオロ−Ｃ_２〜Ｃ_４−アルキル、アリール−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ又はＣ_１〜Ｃ_４−アルコキシであり、
Ｒ３は、水素、ハロゲン、フルオロ−Ｃ_１〜Ｃ_４−アルキル、カルボキシル、−ＣＯ−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、シアノ、基−ＣＯ−ＮＲ３１Ｒ３２、基ＳＯ_２−ＮＲ３１Ｒ３２又は基Ｈｅｔであり、その際、
Ｒ３１は、水素、ヒドロキシル、Ｃ_１〜Ｃ_７−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル又はＣ_３〜Ｃ_７−シクロアルキル、アミノであり、かつ
Ｒ３２は、水素、Ｃ_１〜Ｃ_７−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルであるか、又は
Ｒ３１及びＲ３２は、一緒になって、その両者が結合される窒素原子を含んで、ピロリジノ基、ピペリジノ基、ピペラジノ基、Ｎ−Ｃ_１〜Ｃ_４−アルキルピペラジノ基、モルホリノ基、アジリジノ基又はアゼチジノ基であり、かつ
Ｈｅｔは、Ｒ３３、Ｒ３４及びＲ３５により置換された、オキサジアゾール、ジヒドロオキサゾール、ジヒドロイミダゾール、オキサゾール、イミダゾール、イソキサゾール、ジヒドロイソキサゾール、ピラゾール及びテトラゾールからなる群から選択される複素環基であり、その際、
Ｒ３３は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_２〜Ｃ_４−アルケニルオキシ、Ｃ_１〜Ｃ_４−アルキルカルボニル、カルボキシル、Ｃ_１〜Ｃ_４−アルコキシカルボニル、カルボキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル−Ｃ_１〜Ｃ_４−アルキル、ハロゲン、ヒドロキシ、アリール、アリール−Ｃ_１〜Ｃ_４−アルキル、アリールオキシ、アリール−Ｃ_１〜Ｃ_４−アルコキシ、トリフルオロメチル、ニトロ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はスルホニルであり、
Ｒ３４は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｒ３５は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｘは、Ｏ（酸素）又はＮＨであり、
Ａｒは、Ｒ４、Ｒ５、Ｒ６及びＲ７により置換された、フェニル、ナフチル、ピロリル、ピラゾリル、イミダゾリル、１，２，３−トリアゾリル、インドリル、ベンゾイミダゾリル、フリル、ベンゾフリル、チエニル、ベンゾチエニル、チアゾリル、イソキサゾリル、ピリジニル、ピリミジニル、キノリニル及びイソキノリニルからなる群から選択される、単環式もしくは二環式の芳香族基であり、
Ｒ４は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_２〜Ｃ_４−アルケニルオキシ、Ｃ_１〜Ｃ_４−アルキルカルボニル、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、カルボキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル−Ｃ_１〜Ｃ_４−アルキル、ハロゲン、ヒドロキシ、アリール、アリール−Ｃ_１〜Ｃ_４−アルキル、アリールオキシ、アリール−Ｃ_１〜Ｃ_４−アルコキシ、トリフルオロメチル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ、ニトロ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はスルホニルであり、
Ｒ５は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｒ６は、水素、Ｃ_１〜Ｃ_４−アルキル又はハロゲンであり、かつ
Ｒ７は、水素、Ｃ_１〜Ｃ_４−アルキル又はハロゲンであり、
アリールは、フェニル又は、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル、ニトロ、トリフルオロメトキシ、ヒドロキシ及びシアノの群からの１個、２個又は３個の同一又は異なる置換基で置換されたフェニルである］で示される化合物及びこれらの化合物の塩に関する。

[Where:
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxyl , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxy carbonylation Ruamino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH;
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 A monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl;
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
Aryl is phenyl _or, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy, _carboxy, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and a group of cyano From 1, 2 or 3 of the same or different substituents, and the salts of these compounds.

In a further aspect, the present invention is represented by formula 1a, wherein:
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH;
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 A monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl;
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
Aryl is phenyl _or, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy, _carboxy, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and a group of cyano Phenyl substituted with 1, 2 or 3 identical or different substituents from
R3 is, R1 and R2 are hydrogen or _C 1 -C ₄ - means an alkyl, and Ar is phenyl or _C 1 -C ₄ - in the case of phenyl substituted by alkoxy group, the compound does not denote hydrogen, and their Relates to a salt of the compound.

In a further aspect, the present invention is represented by formula 1a, wherein:
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonyl _amino, C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or Is nil,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH;
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 A monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl;
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
Aryl is phenyl _or, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy, _carboxy, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and a group of cyano Phenyl substituted with 1, 2 or 3 identical or different substituents from
R3 is, R1 is _hydrogen, C 1 -C ₄ - alkyl or hydroxy _-C 1 -C ₄ - alkyl, and R2 is _hydrogen, C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl -C _{When it is 1} -C ₄ -alkyl, it relates to compounds which do not imply hydrogen or halogen and salts of these compounds.

  In another embodiment, the present invention provides compounds of formula 1b

［式中、
Ｒ１は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_３〜Ｃ_７−シクロアルキル、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル、Ｃ_２〜Ｃ_４−アルケニル、Ｃ_２〜Ｃ_４−アルキニル、フルオロ−Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ又はＣ_１〜Ｃ_４−アルキルカルボニルオキシ−Ｃ_１〜Ｃ_４−アルキルであり、
Ｒ２は、水素、Ｃ_１〜Ｃ_４−アルキル、アリール、Ｃ_３〜Ｃ_７−シクロアルキル、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、フルオロ−Ｃ_２〜Ｃ_４−アルキル、アリール−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ又はＣ_１〜Ｃ_４−アルコキシであり、
Ｒ３は、水素、ハロゲン、フルオロ−Ｃ_１〜Ｃ_４−アルキル、カルボキシル、−ＣＯ−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、シアノ、基−ＣＯ−ＮＲ３１Ｒ３２、基ＳＯ_２−ＮＲ３１Ｒ３２又は基Ｈｅｔであり、その際、
Ｒ３１は、水素、ヒドロキシル、Ｃ_１〜Ｃ_７−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル又はＣ_３〜Ｃ_７−シクロアルキル、アミノであり、かつ
Ｒ３２は、水素、Ｃ_１〜Ｃ_７−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルであるか、又は
Ｒ３１及びＲ３２は、一緒になって、その両者が結合される窒素原子を含んで、ピロリジノ基、ピペリジノ基、ピペラジノ基、Ｎ−Ｃ_１〜Ｃ_４−アルキルピペラジノ基、モルホリノ基、アジリジノ基又はアゼチジノ基であり、かつ
Ｈｅｔは、Ｒ３３、Ｒ３４及びＲ３５により置換された、オキサジアゾール、ジヒドロオキサゾール、ジヒドロイミダゾール、オキサゾール、イミダゾール、イソキサゾール、ジヒドロイソキサゾール、ピラゾール及びテトラゾールからなる群から選択される複素環基であり、その際、
Ｒ３３は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_２〜Ｃ_４−アルケニルオキシ、Ｃ_１〜Ｃ_４−アルキルカルボニル、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、カルボキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル−Ｃ_１〜Ｃ_４−アルキル、ハロゲン、ヒドロキシ、アリール、アリール−Ｃ_１〜Ｃ_４−アルキル、アリールオキシ、アリール−Ｃ_１〜Ｃ_４−アルコキシ、トリフルオロメチル、ニトロ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はスルホニルであり、
Ｒ３４は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｒ３５は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｘは、Ｏ（酸素）又はＮＨであり、かつ
Ｚは、−ＣＨＲ８−又は−ＣＨＲ８−ＣＨＲ９−の意味を有し、その際、
Ｒ４は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_２〜Ｃ_４−アルケニルオキシ、Ｃ_１〜Ｃ_４−アルキルカルボニル、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、カルボキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシカルボニル−Ｃ_１〜Ｃ_４−アルキル、ハロゲン、ヒドロキシ、アリール、アリール−Ｃ_１〜Ｃ_４−アルキル、アリールオキシ、アリール−Ｃ_１〜Ｃ_４−アルコキシ、トリフルオロメチル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ、ニトロ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はスルホニルであり、
Ｒ５は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル又はヒドロキシであり、
Ｒ８は、水素、Ｃ_１〜Ｃ_７−アルキル、Ｃ_２〜Ｃ_７−アルケニル、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、
Ｒ９は、水素、Ｃ_１〜Ｃ_７−アルキル、Ｃ_２〜Ｃ_７−アルケニル、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、かつ
アリールは、フェニル又は、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、カルボキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、ハロゲン、トリフルオロメチル、ニトロ、トリフルオロメトキシ、ヒドロキシ及びシアノの群からの１個、２個又は３個の同一又は異なる置換基で置換されたフェニルである］で示される化合物及びこれらの化合物の塩に関する。

[Where:
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH, and Z has the meaning -CHR8- or -CHR8-CHR9-,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R8 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
R9 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy and aryl is phenyl _or, C 1 -C ₄ - 1, 2 or 3 identical from the group of alkyl, C ₁ -C ₄ -alkoxy, carboxy, C ₁ -C ₄ -alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and cyano Or phenyl substituted with a different substituent] and salts of these compounds Related.

  Compounds of formula 1b have up to 3 chiral centers in the parent structure. Thus, the present invention relates to all possible stereoisomers (including pure enantiomers which are an advantageous subject of the present invention) at all desired mixing ratios with one another.

  Of the compounds of formula 1a, preferred compounds are those of formula 1a-1

［式中、
Ｒ１は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_３〜Ｃ_７−シクロアルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルであり、
Ｒ２は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ、Ｃ_１〜Ｃ_４−アルコキシ又はアリール−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルであり、
Ｒ３は、カルボキシル、−ＣＯ−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、シアノ、基−ＣＯ−ＮＲ３１Ｒ３２、基ＳＯ_２−ＮＲ３１Ｒ３２又は基Ｈｅｔであり、その際、
Ｒ３１は、水素、Ｃ_１〜Ｃ_７−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_３〜Ｃ_７−シクロアルキル又はアミノであり、
Ｒ３２は、水素又はＣ_１〜Ｃ_７−アルキルであるか、又は
Ｒ３１及びＲ３２は、一緒になって、その両者が結合される窒素原子を含んで、ピロリジノ基、ピペリジノ基、ピペラジノ基、Ｎ−Ｃ_１〜Ｃ_４−アルキルピペラジノ基、モルホリノ基、アジリジノ基又はアゼチジノ基であり、かつ
Ｈｅｔは、Ｒ３３、Ｒ３４及びＲ３５により置換された、オキサジアゾール、ジヒドロオキサゾール及びジヒドロイミダゾールからなる群から選択される複素環基であり、その際、
Ｒ３３は、水素又はＣ_１〜Ｃ_４−アルキルであり、
Ｒ３４は、水素又はＣ_１〜Ｃ_４−アルキルであり、
Ｒ３５は、水素又はＣ_１〜Ｃ_４−アルキルであり、
Ｒ４は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシカルボニル、トリフルオロメチル、フルオロ−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノであり、
Ｒ５は、水素、Ｃ_１〜Ｃ_４−アルキル又はＣ_１〜Ｃ_４−アルコキシであり、かつ
Ｘは、Ｏ（酸素）又はＮＨである］で示される化合物及びこれらの化合物の塩である。

[Where:
R1 is _hydrogen, C 1 -C ₄ - _alkyl, C 3 -C ₇ - cycloalkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _hydroxy, C 1 -C ₄ - alkoxy or aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl,
R3 is carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, The group SO ₂ —NR 31 R 32 or the group Het,
R31 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 3 -C ₇ - cycloalkyl or amino Yes,
R32 is hydrogen or C ₁ -C ₇ -alkyl, or R31 and R32 taken together include the nitrogen atom to which they are attached, including a pyrrolidino group, piperidino group, piperazino group, N- C ₁ -C ₄ -alkylpiperazino group, morpholino group, aziridino group or azetidino group, and Het is from the group consisting of oxadiazole, dihydrooxazole and dihydroimidazole substituted by R33, R34 and R35 A selected heterocyclic group, wherein
R33 is hydrogen or _C 1 -C ₄ - alkyl,
R34 is hydrogen or _C 1 -C ₄ - alkyl,
R35 is hydrogen or _C 1 -C ₄ - alkyl,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxycarbonyl, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy -C ₁ an alkoxycarbonylamino, - -C ₄
R5 is _hydrogen, C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy, and X is a salt of O (oxygen) or compounds and these compounds represented by a is] NH.

Of the compounds of formula 1a, particularly advantageous compounds are represented by formula 1a-1, in which
R1 is _hydrogen, C 1 -C ₄ - alkyl or hydroxy _-C 1 -C ₄ - alkyl,
R2 is hydrogen or _C 1 -C ₄ - alkyl,
R3 is carboxyl, —CO—C ₁ -C ₄ -alkoxy, hydroxy-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl or the group —CO—NR 31 R 32, that time,
R31 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, and R32 is hydrogen or _C 1 -C ₇ - alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino, piperidino, piperazino, N -C ₁ -C ₄ - alkyl piperazino group, a morpholino group, an aziridino group, or an azetidino group,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxycarbonyl, trifluoromethyl, amino, mono- - or di -C ₁ -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl amino,
R5 is _hydrogen, C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy, and X is a salt of O (oxygen) or compounds and these compounds is NH.

The highlighted compound is represented by Formula 1a-1, wherein
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is carboxyl, —CO—C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl or the group —CO—NR 31 R 32,
R31 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, And R32 is hydrogen or C ₁ -C ₄ -alkyl, or R 31 and R 32 together contain a nitrogen atom to which both are attached, and are pyrrolidino, piperidino, piperazino, N -C ₁ -C ₄ - alkyl piperazino group, a morpholino group, an aziridino group, or an azetidino group,
R4 _is, C 1 -C ₄ - alkylcarbonyl amino, - alkyl or _C 1 -C ₄
R5 _is, C 1 -C ₄ - alkyl,
X is a compound which is O (oxygen) or NH and a salt thereof.

Also highlighted are compounds of formula 1a-1, in which:
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is carboxyl, —CO—C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl or the group —CO—NR 31 R 32,
R31 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, and R32 is hydrogen or _C 1 -C ₄ - alkyl,
R4 _is, C 1 -C ₄ - alkylcarbonyl amino, - alkyl or _C 1 -C ₄
R5 _is, C 1 -C ₄ - alkyl,
X is a compound which is O (oxygen) or NH and a salt thereof.

Also particularly emphasized are compounds of formula 1a-1, in which
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is a group —CO—NR31R32,
R31 _is C 1 -C ₄ - alkyl, and R32 _is C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded A pyrrolidino group,
R4 _is, C 1 -C ₄ - alkyl,
R5 _is, C 1 -C ₄ - alkyl,
X is a compound that is NH and salts thereof.

Also particularly emphasized are compounds of formula 1a-1, in which
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is a group —CO—NR31R32,
R31 _is, C 1 -C ₄ - alkyl, and R32 _is, C 1 -C ₄ - alkyl,
R4 _is, C 1 -C ₄ - alkyl,
R5 _is, C 1 -C ₄ - alkyl,
X is a compound that is NH and salts thereof.

  Of the compounds of formula 1b, preferred compounds are those of formula 1b-1

［式中、
Ｒ１は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_３〜Ｃ_７−シクロアルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルであり、
Ｒ２は、水素、Ｃ_１〜Ｃ_４−アルキル、ヒドロキシ、Ｃ_１〜Ｃ_４−アルコキシ又はアリール−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルであり、
Ｒ３は、カルボキシル、−ＣＯ−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、シアノ、基−ＣＯ−ＮＲ３１Ｒ３２、基ＳＯ_２−ＮＲ３１Ｒ３２又は基Ｈｅｔであり、その際、
Ｒ３１は、水素、Ｃ_１〜Ｃ_７−アルキル、ヒドロキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキル、Ｃ_３〜Ｃ_７−シクロアルキル又はアミノであり、かつ
Ｒ３２は、水素又はＣ_１〜Ｃ_７−アルキルであるか、又は
Ｒ３１及びＲ３２は、一緒になって、その両者が結合される窒素原子を含んで、ピロリジノ基、ピペリジノ基、ピペラジノ基、Ｎ−Ｃ_１〜Ｃ_４−アルキルピペラジノ基、モルホリノ基、アジリジノ基又はアゼチジノ基であり、かつ
Ｈｅｔは、Ｒ３３、Ｒ３４及びＲ３５により置換された、オキサジアゾール、ジヒドロオキサゾール及びジヒドロイミダゾールからなる群から選択される複素環基であり、その際、
Ｒ３３は、水素又はＣ_１〜Ｃ_４−アルキルであり、
Ｒ３４は、水素又はＣ_１〜Ｃ_４−アルキルであり、
Ｒ３５は、水素又はＣ_１〜Ｃ_４−アルキルであり、
Ｒ４は、水素、Ｃ_１〜Ｃ_４−アルキル、Ｃ_１〜Ｃ_４−アルコキシ又はハロゲンであり、
Ｒ５は、水素又はＣ_１〜Ｃ_４−アルキルであり、
Ｒ８は、ヒドロキシル、Ｃ_１〜Ｃ_４−アルコキシ、オキソ置換されたＣ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ、ヒドロキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_３〜Ｃ_７−シクロアルキル−Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシ、Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、ハロゲン−Ｃ_１〜Ｃ_４−アルコキシ、アミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ、Ｃ_１〜Ｃ_４−アルキルカルボニルアミノ、Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ、モノ−もしくはジ−Ｃ_１〜Ｃ_４−アルキルアミノ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシ、Ｃ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルコキシカルボニルアミノ又はＣ_１〜Ｃ_４−アルコキシ−Ｃ_１〜Ｃ_４−アルキルカルボニルオキシであり、
Ｘは、Ｏ（酸素）又はＮＨである］で示される化合物及びそれらの塩である。

[Where:
R1 is _hydrogen, C 1 -C ₄ - _alkyl, C 3 -C ₇ - cycloalkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _hydroxy, C 1 -C ₄ - alkoxy or aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl,
R3 is carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, The group SO ₂ —NR 31 R 32 or the group Het,
R31 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 3 -C ₇ - cycloalkyl or amino There and R32 is hydrogen or _C 1 -C ₇ - alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group N—C ₁ -C ₄ -alkylpiperazino, morpholino, aziridino or azetidino and Het is substituted by R33, R34 and R35, from oxadiazole, dihydrooxazole and dihydroimidazole A heterocyclic group selected from the group consisting of:
R33 is hydrogen or _C 1 -C ₄ - alkyl,
R34 is hydrogen or _C 1 -C ₄ - alkyl,
R35 is hydrogen or _C 1 -C ₄ - alkyl,
R4 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy or halogen,
R5 is hydrogen or _C 1 -C ₄ - alkyl,
R8 is _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - _cycloalkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy , hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy C ₃ -C ₇ -cycloalkoxy-C ₁ -C ₄ -alkoxy, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkyl carbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonyl A _Roh, C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - _{alkylcarbonyloxy,} C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
X is O (oxygen) or NH] and their salts.

Particularly advantageous compounds are represented by formula 1b-1, in which
R1 is _hydrogen, C 1 -C ₄ - alkyl or hydroxy _-C 1 -C ₄ - alkyl,
R2 is hydrogen or _C 1 -C ₄ - alkyl,
R3 is carboxyl, —CO—C ₁ -C ₄ -alkoxy, hydroxy-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl or the group —CO—NR 31 R 32, that time,
R31 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, and R32 is hydrogen or _C 1 -C ₇ - alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino, piperidino, piperazino, N -C ₁ -C ₄ - alkyl piperazino group, a morpholino group, an aziridino group, or an azetidino group,
R4 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy or halogen,
R5 is hydrogen or alkyl;
R8 is _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - _cycloalkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy , hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy C ₃ -C ₇ -cycloalkoxy-C ₁ -C ₄ -alkoxy, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkyl carbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonyl A _Roh, C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - _{alkylcarbonyloxy,} C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
X is a compound which is O (oxygen) or NH and a salt thereof.

Further particularly advantageous compounds are represented by formula 1b-1, in which
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is carboxyl, —CO—C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl or the group —CO—NR 31 R 32,
R31 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, and R32 is hydrogen or _C 1 -C ₄ - alkyl,
R4 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy or halogen,
R5 is hydrogen;
R8 is _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - _cycloalkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy , hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy C ₃ -C ₇ -cycloalkoxy-C ₁ -C ₄ -alkoxy, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkyl carbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonyl A _Roh, C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - _{alkylcarbonyloxy,} C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
X is a compound which is O (oxygen) or NH and a salt thereof.

Further particularly advantageous compounds are represented by formula 1b-1, in which
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is carboxyl, —CO—C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkyl or the group —CO—NR 31 R 32,
R31 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, and R32 is hydrogen or _C 1 -C ₄ - alkyl,
R4 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy or halogen,
R5 is hydrogen;
R8 is hydroxyl or _C 1 -C ₄ - alkoxy,
X is a compound which is O (oxygen) or NH and a salt thereof.

The highlighted compound is represented by formula 1b-1, in which
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is a group —CO—NR31R32,
R31 _is, C 1 -C ₄ - alkyl, and R32 _is, C 1 -C ₄ - alkyl,
R4 is hydrogen;
R5 is hydrogen;
R8 is hydroxyl;
X is a compound which is O (oxygen) and a salt thereof.

  The compound of general formula 1a, as shown in Reaction Scheme 1, is a substituted benzimidazole compound of Formula 2 and Formula 3, wherein L is a suitable leaving group, such as a suitable halogen atom, For example, it can be obtained by reacting with a compound which is chlorine.

  Reaction formula 1:

  Another method for preparing the compound of formula 1a, wherein X is NH, is represented by the general formula 2, wherein X is NH and a substituted benzimidazole compound: And the subsequent imine intermediate is reduced with a suitable reducing agent such as sodium borohydride (reductive amination, Scheme 2).

  Reaction formula 2:

  Similarly, a compound of general formula 1b is a 1,2-epoxyindane (compound 1b-1) having a substituted benzimidazole of formula 2 and any desired substituents R4 and R5 of formula 5. Can be obtained by reacting with (see Formula 3). 1,2-epoxyindane is, for example, W.W. F. Whitmore; I. Gebhart, J .; Am. Chem. Soc. 1942, 64, 912. In general, substituted alkyl-, alkoxy- or halogeno-epoxyindanes can be prepared from the corresponding substituted indans by methods known from the literature (for example epoxidation).

  Reaction formula 3:

  A starting compound of formula 2 in which X is O can be obtained, for example, according to the reaction sequence shown in Scheme 4. The compound of Formula 6 is deprotonated with a suitable base, such as n-butyllithium, followed by a suitable R2 precursor, R2-Lg (which precursor R2-Lg is a suitable leaving group Lg, such as Reaction with a halogen atom, for example an R2 group substituted with an iodine atom). The above reaction yields a compound of formula 7, which is converted by methods known to those skilled in the art to obtain the desired compound represented by formula 2, wherein X is O (oxygen). Can do.

  Reaction formula 4:

  A compound of formula 6 can be prepared from a compound of formula 8 according to, for example, the reaction sequence shown in Reaction Scheme 5.

  Reaction formula 5:

3-Nitro-2-aminophenol can be reacted in a first step with a suitable benzyl derivative, such as benzyl chloride, to form a reaction product of formula 9, which can be prepared, for example, according to J. Am. Heterocyclic Chem. (1983), 20, 1525. The substituent R3 can be introduced into the compound of formula 9, for example the bromine substituent can be introduced by bromination reaction using a suitable bromination reagent such as N-bromosuccinimide. Subsequent reduction of the compound of formula 10 under standard conditions, for example with hydrazine N ₂ H ₄ , in the presence of FeCl ₃ forms the compound of formula 11, which is known to those skilled in the art. The method can be transformed, for example, by a cyclization reaction with a diketone of formula 12, to give a benzimidazole derivative of formula 6.

A starting compound of formula 2 in which X is NH can be obtained, for example, according to the reaction sequence shown in Scheme 6. Starting from the substituted dinitrochlorobenzene of formula 13 and reacting with a primary amine of formula 14, the compound of formula 15 (LA Summers, Austr. J. Chem. 1965, 18, 1695-1698). And the compound is reduced by methods known to those skilled in the art to give the phenylenediamine of formula 16. The benzimidazole of formula 2 is then cyclized from the compound of formula 16 with, for example, a diketone of formula 12 to give a compound of formula 17, and its NO ₂ group is subsequently known from catalytic hydrogenation or literature. It can obtain by reducing by another method (Scheme 6).

  Reaction formula 6:

The reaction steps outlined above are carried out in a manner known per se, for example as described in more detail in the examples. Derivatization of compounds obtained according to the above reaction schemes 1, 2 and 3 (eg converting one group R3 to another group R3, or converting a group R2 which is H to another group R2, or a hydroxyl group Is converted to an alkoxy group or an ester group, if necessary, it is likewise carried out as known to the expert. If a compound in which R3 is —CO—C ₁ -C ₄ -alkoxy or R3 is —CO—NR31R32 is desired, suitable derivatization is known as known to the expert (eg correspondingly May be carried out at the stage of the benzimidazole of formula 2 (Schemes 1, 2 and 3) or at a later point in time.

Excellent effect The excellent gastric protective action and gastric acid secretion-inhibiting action of the compound according to the present invention can be shown in an examination by an animal experimental model. In the examples, the compounds of the formula 1 according to the invention examined in the model described below are numbered corresponding to the numbers of these compounds.

Tests on the inhibitory action on the perfused rat stomach Table A below shows the in vivo effects of the compounds of formula 1 according to the invention on the acid secretion stimulated by pentagastrin in the perfused rat stomach after intraduodenal administration. Show the impact.

Table A

Method The abdomen of anesthetized rats (CD rat, female, 200-250 g; 1.5 g / kg im urethane) was opened with a midline upper abdominal incision after tracheotomy, and a PVC catheter was orally fixed to the esophagus. And another catheter was secured through the pylorus so that the end of the tube was placed just in the gastric lumen. The catheter passing through the pylorus led to the outer right abdominal wall through the lateral opening.

  After thorough washing (approximately 50-100 ml), warm (37 ° C.) physiological NaCl solution was continuously passed through the stomach (0.5 ml / min, pH 6.8-6.9; Braun-Unita I). By titrating with pH (pH meter 632, glass electrode EA147; φ = 5 mm, Metrohm) and a freshly prepared 0.01 N NaOH solution to pH 7 (Dosimat 665 Metrohm), the secreted HCl was in each case. Measurements were made on the effluent collected at 15 minute intervals.

  Gastric secretion was simultaneously performed at 1 μg / kg (= 1.65 ml / h) of intravenous pentagastrin (left femoral vein) approximately 30 minutes after the end of the surgery (ie after measurement of two preliminary fractions). Stimulated by infusion. The substance to be tested was administered into the duodenum at a liquid volume of 2.5 ml / kg 60 minutes after the start of continuous infusion of pentagastrin. The animal's body temperature was maintained at a constant 37.8-38 ° C. by infrared irradiation and a heating pad (automatic, stepless control by rectal temperature sensor).

The following examples serve to illustrate the invention in more detail without restricting it. Other compounds of formula 1 whose production methods are not specified can be prepared in the same manner or in a manner known to those skilled in the art using conventional processing techniques. The compounds specifically named by way of example and the salts of these compounds are an advantageous subject of the present invention. The abbreviation min represents minutes, h represents hours, m. p. Represents the melting point and ee represents the enantiomeric excess.

I. Final compound of formula 1 7- (trans-2,3-dihydro-2-hydroxy-1-indenyloxy) -5- (N, N-dimethylaminocarbonyl) -1,2-dimethyl-1H-benzimidazole 0.38 g (1. 63 mmol) 7-hydroxy-1,2-dimethyl-1H-benzimidazole-5-carboxylic acid dimethylamide and 0.8 g (6.1 mmol) 1,2-epoxyindane with 4 ml methanol and 1 ml To the suspension in water, 0.45 ml of triethylamine was added and the mixture was heated at 70 ° C. for 1 hour. The cooled solution was separated between dichloromethane and water. The organic layer was separated, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel with dichloromethane: methanol (13: 1) and crystallized from ethyl acetate to give 0.45 g (76%) of the title compound as a colorless solid ( The melting point was 230 ° C.).

2. 6- (N, N-dimethylaminocarbonyl) -4- (2,6-dimethylbenzylamino) -2,3-dimethyl-3H-benzimidazole 0.54 g (1.56 mmol) of 6- (N, N -Dimethylaminocarbonyl) -4- (2,6-dimethyl-benzylidene-amino) -2,3-dimethyl-3H-benzimidazole in a solution of 10 ml of methanol in 0.09 g (2.38 mmol) Of sodium borohydride was slowly added. After 10 minutes, the reaction mixture was partitioned between saturated aqueous ammonium chloride and dichloromethane. The organic layer is separated, dried over anhydrous magnesium sulfate and evaporated. The residue was crystallized from ethyl acetate / n-heptane to give 0.52 g (95%) of the title compound as a colorless solid (mp 187-188 ° C.).

3. 4- (2,6-Dimethyl-benzylamino) -2,3-dimethyl-6- (N-pyrrolidinocarbonyl) -3H-benzimidazole 0.5 g (1.94 mmol) 4-amino-2,3 A solution of dimethyl-6- (N-pyrrolidinocarbonyl) -3H-benzimidazole and 0.39 g (2.9 mmol) of 2,6-dimethylbenzaldehyde in 15 ml of dichloromethane and 5 ml of acetic acid. 0.82 mg (3.9 mmol) of sodium triacetoxyborohydride was added. After 2 hours, TLC showed incomplete reaction and the mixture was evaporated to dryness. The residue was dissolved in 20 ml of methanol and treated with excess sodium borohydride. After the reaction was complete, the mixture was partitioned between saturated aqueous ammonium chloride and dichloromethane. The organic layer is separated, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel with dichloromethane: methanol (20: 1) and crystallized from ethyl acetate / n-heptane to give 0.41 g (56%) of the title compound as colorless. As a solid (melting point: 188-189 ° C.).

II. Starting compounds A. 2-benzyloxy-4-bromo-6-nitroaniline 50 g (325 mmol) 2-amino-3-nitrophenol, 45 g (325 mmol) potassium carbonate and 2 g (13 mmol) sodium iodide in 400 ml ethanol To the suspension in was added 47 ml (408 mmol) of benzyl chloride and the mixture was heated to 80 ° C. After 2 hours, the reaction mixture was cooled and the solvent was evaporated. The residue was dissolved in ethyl acetate and extracted with water. The organic layer was dried over anhydrous magnesium sulfate and evaporated. Coevaporation with dichloromethane gave a dark brown oily residue that was dissolved in 400 ml of acetonitrile. After adding 63.4 g (356 mmol) of N-bromosuccinimide, the reaction mixture was refluxed for 1 hour. After cooling, 400 g of silica gel was added and the mixture was evaporated to dryness. The resulting solid was loaded onto the column and the product was eluted with ethyl acetate / light petroleum ether (4: 1). Evaporation of the eluate gave a solid that was recrystallized from ethyl acetate / n-heptane to give 62 g (59%) of the title compound as a red solid (melting point 90 ° C.).

B. 2-Amino-3-benzyloxy-5-bromoaniline Suspension of 3.23 g (10 mmol) 2-benzyloxy-4-bromo-6-nitroaniline in 60 ml methanol and 15 ml concentrated hydrochloric acid To this was added 2.23 g (40 mmol) of iron filings in small portions at 60 ° C. After 10 minutes, the mixture was cooled and neutralized with 6N aqueous sodium hydroxide. Activated carbon was added and the suspension was filtered. The filtrate was separated between dichloromethane and water. The organic layer is dried over anhydrous magnesium sulfate and evaporated. The residue was crystallized from ethyl acetate / n-heptane to give 2.05 g (70%) of the title compound as a colorless solid (melting point 108 ° C.).

C. 4-Benzyloxy-6-bromo-2-methyl-1H-benzimidazole 2.0 g (6.82 mol) 2-amino-3-benzyloxy-5-bromo-aniline was placed in 20 ml ethanol. To the suspension was added 5 ml of 5N hydrochloric acid. The reaction mixture was heated to 60 ° C. and 1.41 ml (13.6 mol) of 2,4-pentanedione was added in one portion. After refluxing for 1 hour, the mixture was cooled and neutralized with 6N aqueous sodium hydroxide. The mixture was separated between dichloromethane and water. The organic layer is dried over anhydrous magnesium sulfate and evaporated. The residue was crystallized from ethyl acetate / n-heptane to give 2.12 g (98%) of the title compound as a colorless solid (mp 174 ° C.).

D. 7-benzyloxy-2-methyl-3H-benzimidazole-5-carboxylic acid dimethylamide 2.0 g (6.3 mmol) of 4-benzyloxy-6-bromo-2-methyl-1H-benzimidazole To a suspension in dimethylamine (3.2 M in tetrahydrofuran) was added 210 mg (0.95 mmol) palladium (II) acetate and 495 mg (1.9 mmol) triphenylphosphine. The mixture was transferred into an autoclave and carbonylated (carbon monoxide pressure 5 bar, 120 ° C.) over 16 hours. The reaction mixture was cooled and evaporated. The residue was generated by column chromatography on silica gel with dichloromethane / methanol (13: 1) to give 1.53 g (79%) of the title compound as a light brown oil that was subsequently Used in the step without further purification.

E. 7-Benzyloxy-1,2-dimethyl-1H-benzimidazole-5-carboxylic acid dimethylamide 1.53 g (4.7 mmol) of 7-benzyloxy-2-methyl-3H-benzimidazole-5-carboxylic acid To a solution of dimethylamide in 25 ml of anhydrous tetrahydrofuran, 3.1 ml (5 mmol) of n-butyllithium (1.6 M in hexane) was slowly added at -78 ° C. After addition of 0.32 ml (5.1 mmol) of methyl iodide, the reaction mixture was warmed to room temperature. After 16 hours, the mixture was allowed to separate between dichloromethane and water. The organic layer was separated, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel with dichloromethane / methanol (13: 1) and crystallized from ethyl acetate / n-heptane to give 0.79 g (52%) of the title compound as colorless. As a solid (melting point: 117-118 ° C.).

F. 7-hydroxy-1,2-dimethyl-1H-benzimidazole-5-carboxylic acid dimethylamide 0.7 g (2.2 mmol) of 7-benzyloxy-1,2-dimethyl-1H-benzimidazole-5-carbon A solution of acid dimethylamide in 25 ml methanol and 0.1 ml acetic acid was hydrogenated on 0.25 g 10% Pd / C (25 ° C., 1 bar H ₂ ) for 16 h. The catalyst was filtered off and the filtrate was evaporated. The residue was crystallized from ethyl acetate to give 0.44 g (87%) of the title compound as a colorless solid (mp 209 ° C.).

G. 4-Methylamino-3,5-dinitrobenzene-carboxylic acid 25.0 g (101 mmol) 4-chloro-3,5-dinitrobenzene-carboxylic acid was slowly added into 120 ml aqueous methylamine (40%). And the mixture was heated to reflux. After 1 hour, the mixture was cooled and evaporated to dryness. The residue was dissolved in water and the pH was adjusted to a pH of up to 5 by adding 6N hydrochloric acid. The precipitate was collected, washed with water and dried to give 21.6 g (90%) of the title compound as a yellow solid (mp 184-188 ° C.).

H. 1,2-Dimethyl-7-nitro-1H-benzimidazole-5-carboxylic acid 4.0 g (16.6 mmol) of 4-methylamino-3,5-dinitrobenzene-carboxylic acid are placed in 50 ml of ethanol. To the resulting suspension was added 40 ml of 2N aqueous ammonium polysulfide. After 1 hour, excess ethanol was evaporated and the residue was neutralized with 6N hydrochloric acid. The solid was filtered off and the filtrate was evaporated to dryness. The residue was suspended in 100 ml ethanol and 20 ml 5N hydrochloric acid. To the boiling mixture was added 4.1 ml (40 mmol) 2,5-pentanedione. After 4 hours, the solvent was removed and the residue was diluted with water and neutralized with 40% aqueous sodium hydroxide. The precipitate was collected and suspended in 30 ml methanol and 10 ml water. To the mixture was added 0.96 g (40 mmol) lithium hydroxide and the suspension was heated to 70 ° C. After 30 minutes, the pH of the reaction mixture was adjusted to a pH of up to 6 by adding 4N hydrochloric acid. Excess methanol was removed and the precipitate was collected and washed with water to give 0.8 g (21%) of the title compound as a colorless solid (mp 303-305 ° C.).

I. 6- (N, N-dimethylaminocarbonyl) -4- (2,6-dimethyl-benzylidene-amino) -2,3-dimethyl-3H-benzimidazole 0.8 g (3.4 mmol) of 1,2- A suspension of dimethyl-7-nitro-1H-benzimidazole-5-carboxylic acid in 10 ml methanol and 1 ml acetic acid was hydrogenated with palladium on activated carbon (3 hours, 80 ° C.). The reaction mixture was neutralized with 40% aqueous sodium hydroxide and the catalyst was filtered off. The filtrate is evaporated and the residue is redissolved in 15 ml methanol and 10 ml acetic acid and treated with 2,6-dimethylbenzaldehyde to give the corresponding imine, which is taken up in 10 ml dimethylformamide. And dissolved in 10 ml of dichloromethane. To the solution was added 1.5 g (4.7 mmol) O- (1H-benzotriazol-1-yl) -N, N, N ′, N′-tetramethyl-uronium tetrafluoroborate (TBTU). And the mixture was heated to 50 ° C. After 20 minutes, 5 ml (10 mmol) dimethylamine (2M in tetrahydrofuran) was added at ambient temperature. After 30 minutes, the reaction mixture was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organic layer is separated, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel with dichloromethane: methanol (10: 1) and crystallized from ethyl acetate / n-heptane to yield 0.6 g (51%) of the title compound Obtained as a yellow solid (mp. 165-166 ° C.).

J. et al. 4-methylamino-3,5-dinitro-N-pyrrolidinyl-benzamide 2.0 g (8.3 mmol) 4-methylamino-3,5-dinitrobenzene-carboxylic acid and 4.0 g (12.4 mmol) Of O- (1H-benzotriazol-1-yl) -N, N, N ′, N′-tetramethyl-uronium tetrafluoroborate (TBTU) in 25 ml of chloroform. 5 ml (30 mmol) of pyrrolidine was added at 45 ° C. After 30 minutes, an additional amount of 4.0 g TBTU and 2.5 ml pyrrolidine was added and stirring was continued for 45 minutes. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organic layer is separated, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel with dichloromethane: methanol (100: 1) and crystallized from ethyl acetate / n-heptane to give 1.72 g (70%) of the title compound in orange As a solid (melting point: 148-150 ° C.).

K. 2,3-Dimethyl-4-nitro-6- (N-pyrrolidinocarbonyl) -3H-benzimidazole 1.65 g (5.6 mmol) 4-methylamino-3,5-dinitro-N-pyrrolidinyl-benzamide And to a mixture of 330 mg ruthenium on activated carbon (5%) in 30 ml ethanol was slowly added 0.55 ml (11.2 mmol) hydrazine hydrate at 75 ° C. After 1.5 hours, the catalyst was filtered off and the filtrate was evaporated to dryness. The residue was purified by column chromatography on silica gel using dichloromethane: methanol (20: 1). The intermediate product was suspended in 25 ml methanol and 5 ml 5N hydrochloric acid. To the suspension was added 1.15 ml (11.2 mmol) of 2,4-pentanedione at 80 ° C. After 30 minutes, the reaction mixture was allowed to cool, neutralized with 40% aqueous sodium hydroxide, and extracted with dichloromethane. The organic layer is separated, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel with dichloromethane: methanol (20: 1) and crystallized from ethyl acetate / n-heptane to give 0.91 g (56%) of the title compound in orange As a solid (melting point 114-117 ° C.).

L. 4-amino-2,3-dimethyl-6- (N-pyrrolidinocarbonyl) -3H-benzimidazole 0.82 g (2.84 mmol) of 2,3-dimethyl-4-nitro-6- (N-pyrrole) A solution of Dinocarbonyl) -3H-benzimidazole in 20 ml methanol and 1 ml acetic acid was hydrogenated with 300 mg palladium on activated carbon (10%, 2.5 hours, 50 ° C.). The catalyst was filtered off and the reaction mixture was evaporated to dryness. The residue was crystallized with ethyl acetate / n-heptane to give 0.61 g (83%) of a beige solid (mp 250-251 ° C.).

INDUSTRIAL APPLICABILITY The compounds of formula 1 and their salts have useful pharmacological properties that allow commercial use. In particular, the compounds of formula 1 and their salts show marked inhibition of gastric acid secretion and excellent gastric and intestinal protective action in warm-blooded animals, especially humans. In the present context, the compounds according to the invention are characterized by a high selectivity of action, an advantageous duration of action, in particular good intestinal activity, the absence of serious side effects and a wide therapeutic range.

  “Gastrointestinal and intestinal protection” refers herein to gastrointestinal diseases, in particular microorganisms (eg Helicobacter pylori), bacterial toxins, pharmaceuticals (eg certain anti-inflammatory and anti-rheumatic drugs, eg NSAIDs). And COX inhibitors), chemicals (eg, ethanol), gastrointestinal inflammatory diseases and injuries (eg, gastric ulcers, peptic ulcers, eg peptic ulcer bleeding, duodenal ulcers, gastritis, hyperacidity or pharmaceuticals that can be caused by gastric acid or stress environment Is understood to mean the prevention and treatment of functional dyspepsia associated with “Gastric and intestinal protection” is understood according to general knowledge to include gastroesophageal reflux disease (GERD), a condition that includes but is not limited to heartburn and / or reflux.

  In its superior properties, the compounds according to the invention have surprisingly been found to clearly outperform the known compounds from the prior art in various models with established anti-ulcerogenic and antisecretory properties. Due to their properties, the compounds of formula 1 and their pharmacologically acceptable salts are remarkably suitable for use in human medicine and veterinary medicine, in which the compounds and salts are in particular the stomach and / or intestines. It is used for treatment and / or prevention of other diseases.

  Accordingly, another subject of the invention is a compound according to the invention for use in the treatment and / or prevention of the abovementioned diseases.

  The invention likewise relates to the use of the compounds according to the invention for the manufacture of a medicament used for the treatment and / or prevention of the aforementioned diseases.

  The invention further includes the use of the compounds according to the invention for the treatment and / or prevention of the diseases mentioned above.

  Another subject of the invention is a medicament containing one or more compounds of formula 1 and / or pharmacologically acceptable salts thereof.

  The medicament is preferably produced by methods known per se and methods known to those skilled in the art. As a medicament, the pharmacologically active compound according to the invention (= active compound) is itself, or preferably in combination with suitable pharmaceutical auxiliaries or excipients, tablets, coated tablets, capsules, suppositories, Used in the form of patches (eg TTS), emulsions, suspensions or solutions, in which the active compound content is preferably 0.1 to 95% and suitable auxiliaries and excipients By selection, pharmaceutical dosage forms (eg delayed release or enteric forms) which are closely adapted to the active compound and / or closely adapted to the desired onset and / or duration of action can be obtained.

  Suitable auxiliaries and excipients for the desired pharmaceutical formulation are known to the person skilled in the art based on the expertise of the person skilled in the art. In addition to liquids, gel formers, suppository bases, tablet auxiliaries and other active compound excipients, for example, antioxidants, dispersants, emulsifiers, antifoaming agents, flavoring agents, preservatives, solubilizers Colorants, or in particular penetration enhancers and complexing agents (eg cyclodextrins) can be used.

  The active compound can be administered orally, parenterally or transdermally.

  Generally in human medicine, for oral administration, to achieve the desired result at a daily dose of about 0.01 to about 20, preferably 0.05 to 5, especially 0.1 to 1.5 mg / kg body weight It has been found to be advantageous to administer the active compound in multiple, preferably 2 to 4 individual dosage forms where appropriate. In the case of parenteral treatment, similar or generally lower doses can be used, especially when the active compound is administered intravenously. One of ordinary skill in the art can readily determine the optimal dosage and method of administration of the active compound required each time based on his / her expertise.

  When the compounds according to the invention and / or their salts are to be used for the treatment of the abovementioned diseases, the pharmaceutical preparations comprise one or more pharmacologically active ingredients of the group of other drugs, for example: tranquilizers ( E.g. from the group of benzodiazepines, e.g. diazepam), antispasmodic agents (e.g. vitamivelin or camilofin), anticholinergics (e.g. oxyphencyclimine or phencarbamide), local anesthetics (e.g. tetracaine or procaine) and in some cases Furthermore, an enzyme, a vitamin, or an amino acid can also be contained.

What should be emphasized here is in particular the compounds according to the invention and pharmaceuticals which suppress the secretion of acids, such as H ₂ blockers (eg cimetidine, ranitidine), H ⁺ / K ⁺ -ATPase inhibitors. In combination with (for example omeprazole, pantoprazole) or further in combination with so-called peripheral anticholinergic agents (for example pirenzepine, telenzepine), or to enhance the main action in an additional or even additional sense, and In combination with gastrin antagonists aimed at eliminating or reducing side effects, or further antibacterial actives for controlling Helicobacter pylori (eg cephalosporins, tetracyclines, penicillins, macrolides, nitroimidazoles or It is a combination with bismuth salt). Suitable antimicrobial adjuncts that may be mentioned are, for example, mezlocillin, ampicillin, amoxicillin, cephalotin, cefoxitin, cefotaxime, imipenem, gentamicin, amikacin, erythromycin, ciprofloxacin, metronidazole, clarithromycin, azithromycin and combinations thereof (for example Clarithromycin + metronidazole).

  The compounds of formula 1 in combination with pharmaceuticals known to be effective in the development of certain ulcers (eg certain anti-inflammatory and anti-rheumatic drugs such as NSAIDs) in view of their excellent gastric and intestinal protective action Suitable for free or fixed combinations. Furthermore, the compounds of formula 1 are suitable for free or fixed combinations with motility modifiers.

Claims (14)

Formula 1

[Where:
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH and Y has the meaning —CH ₂ —Ar, where
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 Is a monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl, or Y is a group gp

In doing so,
Z means —CHR8— or —CHR8—CHR9—,
In Ar and / or the group gp,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
R8 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
R9 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
Aryl is phenyl _or, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy, _carboxy, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and a group of cyano And phenyl, substituted with 1, 2 or 3 identical or different substituents from and the salts thereof. It is shown by Formula 1, in which
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH and Y has the meaning —CH ₂ —Ar, where
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 Is a monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl, or Y is a group gp

In doing so,
Z means —CHR8— or —CHR8—CHR9—,
In Ar and / or the group gp,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
R8 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
R9 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy and aryl is phenyl _or, C 1 -C ₄ - 1, 2 or 3 identical from the group of alkyl, C ₁ -C ₄ -alkoxy, carboxy, C ₁ -C ₄ -alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and cyano Or phenyl substituted with different substituents, provided that
R3 is, R1 and R2 are hydrogen or _C 1 -C ₄ - has the meaning of alkyl, and Y is CH ₂ - phenyl or _C 1 _{~C 4} - CH ₂ substituted by an alkoxy group - to indicate phenyl The compound according to claim 1, which has no meaning of hydrogen, and a salt thereof. It is shown by Formula 1, in which
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH and Y has the meaning —CH ₂ —Ar, where
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 Is a monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl, or Y is a group gp

In doing so,
Z means —CHR8— or —CHR8—CHR9—,
In Ar and / or the group gp,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
R8 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
R9 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy and aryl is phenyl _or, C 1 -C ₄ - 1, 2 or 3 identical from the group of alkyl, C ₁ -C ₄ -alkoxy, carboxy, C ₁ -C ₄ -alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and cyano Or phenyl substituted with different substituents, provided that
R3 is, R1 is _hydrogen, C 1 ~C ₄ - alkyl or hydroxy _-C 1 -C ₄ - represents an alkyl, R2 is _hydrogen, C 1 ~C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl -C ₁ -C 4 _- represents an alkyl, and Y is to indicate CH 2 _-Ar, no meaning of hydrogen or halogen, the compounds and salts thereof according to claim 1, wherein. Formula 1a

[Where:
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH;
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 A monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl;
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
Aryl is phenyl _or, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy, _carboxy, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and a group of cyano Or a salt thereof according to claim 1, wherein the phenyl is substituted with 1, 2 or 3 identical or different substituents from. Formula 1a, in which
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH;
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 A monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl;
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
Aryl is phenyl _or, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy, _carboxy, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and a group of cyano Phenyl substituted with 1, 2 or 3 identical or different substituents from
R3 is, R1 and R2 are hydrogen or _C 1 -C ₄ - means an alkyl, and Ar is phenyl or _C 1 -C ₄ - in the case of phenyl substituted by alkoxy groups, does not mean hydrogen, claim 4. Compounds according to 4 and salts of these compounds. Formula 1a, in which
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonylamino, _{C 1} -C ₄ - _{alkoxycarbonylamino,} C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonyl Amino or sulfonyl,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH;
Ar is phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzoimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, substituted by R4, R5, R6, and R7 A monocyclic or bicyclic aromatic group selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl and isoquinolinyl;
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R6 is _hydrogen, C 1 -C ₄ - alkyl or halogen, and R7 is _hydrogen, C 1 -C ₄ - alkyl or halogen,
Aryl is phenyl _or, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy, _carboxy, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and a group of cyano Phenyl substituted with 1, 2 or 3 identical or different substituents from
R3 is, R1 is _hydrogen, C 1 -C ₄ - alkyl or hydroxy _-C 1 -C ₄ - represents an alkyl, and R2 is _hydrogen, C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl -C ₁ -C 4 _- to indicate alkyl, does not mean a hydrogen or halogen, the compounds and salts thereof according to claim 4, wherein. 2. A compound of formula 1 according to claim 1, comprising formula 1b.

[Where:
R ₁ is hydrogen, C ₁ -C ₄ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C _1- C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _{alkoxycarbonyl,} C 2 -C ₄ - _alkenyl, C 2 -C ₄ - alkynyl, fluoro _-C 1 -C ₄ - alkyl, hydroxy - C ₁ -C ₄ -alkyl, mono- or di-C ₁ -C ₄ -alkylamino or C ₁ -C ₄ -alkylcarbonyloxy-C ₁ -C ₄ -alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _aryl, C 3 -C ₇ - _cycloalkyl, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, mono- - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyl, hydroxy _-C 1 -C ₄ - alkyl, fluoro _-C 2 -C ₄ - alkyl, aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, hydroxy or _C 1 -C ₄ - alkoxy,
R3 is hydrogen, halogen, fluoro _-C 1 -C ₄ - alkyl, carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy -C ₁ -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, fluoro _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, a group _SO 2 -NR31R32 or the group Het, time,
R31 is hydrogen, _hydroxyl, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl or _C 3 -C ₇ - cycloalkyl, it is amino, and R32 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group, _N-C 1 ~C 4 _- alkylpiperazino, morpholino, aziridino or azetidino And Het is oxadiazole, dihydrooxazole, dihydroimidazole, oxazo substituted by R33, R34 and R35 A heterocyclic group selected from the group consisting of azole, imidazole, isoxazole, dihydroisoxazole, pyrazole and tetrazole,
R33 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, nitro, amino, mono- - or di - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonyl _amino, C 1 ~C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or Is nil,
R34 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R35 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
X is O (oxygen) or NH;
Z means —CHR8— or —CHR8—CHR9—,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 2 -C ₄ - _alkenyloxy, C 1 -C ₄ - alkylcarbonyl, carboxy , _C 1 -C ₄ - alkoxycarbonyl, carboxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl _-C 1 -C ₄ - alkyl, halogen, hydroxy, aryl, _-C 1 -C ₄ - alkyl, aryloxy, aryl _-C 1 -C ₄ - alkoxy, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, nitro, amino, mono- - or di _-C 1 -C ₄ - alkylamino, _{C 1} -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - _{alkoxycarbonylamino,} C 1 -C ₄ - alkoxy - C ₁ -C ₄ -alkoxycarbonylamino or sulfonyl;
R5 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, - _alkoxy, C 1 -C ₄
R8 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
R9 is _hydrogen, C 1 -C ₇ - _alkyl, C 2 -C ₇ - alkenyl, _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - cycloalkyl _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkoxy _-C 1 -C ₄ - _alkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkylcarbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - alkylcarbonyloxy, C ₁ -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
Aryl is phenyl _or, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy, _carboxy, C 1 -C ₄ - alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and a group of cyano And phenyl, substituted with 1, 2 or 3 identical or different substituents from] and salts thereof. A compound of formula 1a according to claim 4, wherein the compound of formula 1a-1

[Where:
R1 is _hydrogen, C 1 -C ₄ - _alkyl, C 3 -C ₇ - cycloalkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _hydroxy, C 1 -C ₄ - alkoxy or aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl,
R3 is carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, The group SO ₂ —NR 31 R 32 or the group Het,
R31 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 3 -C ₇ - cycloalkyl or amino There and R32 is hydrogen or _C 1 -C ₇ - alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group N—C ₁ -C ₄ -alkylpiperazino, morpholino, aziridino or azetidino and Het is substituted by R33, R34 and R35, from oxadiazole, dihydrooxazole and dihydroimidazole A heterocyclic group selected from the group consisting of:
R33 is hydrogen or _C 1 -C ₄ - alkyl,
R34 is hydrogen or _C 1 -C ₄ - alkyl,
R35 is hydrogen or _C 1 -C ₄ - alkyl,
R4 is _hydrogen, C 1 -C ₄ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxycarbonyl, trifluoromethyl, fluoro _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - _{alkylcarbonylamino,} C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy -C ₁ an alkoxycarbonylamino, - -C ₄
R5 is _hydrogen, C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy, and X, the compounds and salts thereof, characterized in that represented by O (oxygen) or NH]. Represented by Formula 1a-1, wherein:
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is a group —CO—NR31R32,
R31 _is C 1 -C ₄ - alkyl, and R32 _is C 1 -C ₄ - alkyl, or R31 and R32 together, including the nitrogen atom to which both are bonded A pyrrolidino group,
R4 _is, C 1 -C ₄ - alkyl,
R5 _is, C 1 -C ₄ - alkyl,
The compounds and salts thereof according to claim 8, wherein X is NH. Represented by Formula 1a-1, wherein:
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is a group —CO—NR31R32,
R31 _is, C 1 -C ₄ - alkyl, and R32 _is, C 1 -C ₄ - alkyl,
R4 _is, C 1 -C ₄ - alkyl,
R5 _is, C 1 -C ₄ - alkyl,
The compounds and salts thereof according to claim 8, wherein X is NH. A compound of formula 1b according to claim 7, which comprises formula 1b-1

[Where:
R1 is _hydrogen, C 1 -C ₄ - _alkyl, C 3 -C ₇ - cycloalkyl, hydroxy _-C 1 -C ₄ - alkyl or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl,
R2 is _hydrogen, C 1 -C ₄ - alkyl, _hydroxy, C 1 -C ₄ - alkoxy or aryl _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl,
R3 is carboxyl, _-CO-C 1 ~C ₄ - alkoxy, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl, cyano, group -CO-NR31R32, The group SO ₂ —NR 31 R 32 or the group Het,
R31 is _hydrogen, C 1 -C ₇ - alkyl, hydroxy _-C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkyl, C 3 -C ₇ - cycloalkyl or amino There and R32 is hydrogen or _C 1 -C ₇ - alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, pyrrolidino group, piperidino group, piperazino group N—C ₁ -C ₄ -alkylpiperazino, morpholino, aziridino or azetidino and Het is substituted by R33, R34 and R35, from oxadiazole, dihydrooxazole and dihydroimidazole A heterocyclic group selected from the group consisting of:
R33 is hydrogen or _C 1 -C ₄ - alkyl,
R34 is hydrogen or _C 1 -C ₄ - alkyl,
R35 is hydrogen or _C 1 -C ₄ - alkyl,
R4 is _hydrogen, C 1 -C ₄ - _alkyl, C 1 -C ₄ - alkoxy or halogen,
R5 is hydrogen or _C 1 -C ₄ - alkyl,
R8 is _hydroxyl, C 1 -C ₄ - alkoxy, _C 1 -C ₄ is oxo-substituted - _alkoxy, C 3 -C ₇ - _cycloalkoxy, C 3 -C ₇ - cycloalkyl _-C 1 -C ₄ - alkoxy , hydroxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - _alkoxy, C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxy C ₃ -C ₇ -cycloalkoxy-C ₁ -C ₄ -alkoxy, C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkoxy-C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkyl carbonyloxy, halogen _-C 1 -C ₄ - alkoxy, amino, mono- - or di _-C 1 -C ₄ - _alkylamino, C 1 -C ₄ - alkylcarbonyl A _Roh, C 1 -C ₄ - alkoxycarbonylamino, mono - or di _-C 1 -C ₄ - alkylamino _-C 1 -C ₄ - _{alkylcarbonyloxy,} C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkoxycarbonylamino or _C 1 -C ₄ - alkoxy _-C 1 -C ₄ - alkyl carbonyloxy,
X is O (oxygen) or NH], and a salt thereof. Represented by formula 1b-1, wherein:
R1 _is, C 1 -C ₄ - alkyl,
R2 _is, C 1 -C ₄ - alkyl,
R3 is a group —CO—NR31R32,
R31 _is, C 1 -C ₄ - alkyl,
R32 _is, C 1 -C ₄ - alkyl,
R4 is hydrogen;
R5 is hydrogen;
R8 is hydroxyl;
12. The compound according to claim 11 and a salt thereof, wherein X is O (oxygen).   A pharmaceutical comprising a conventional pharmaceutical auxiliary and / or excipient together with the compound of claim 1 and / or a pharmaceutically acceptable salt thereof.   Use of the compound according to claim 1 and pharmacologically acceptable salts thereof for the prevention and treatment of gastrointestinal diseases.