ES2591129T3 - Tienopirimidinas - Google Patents

Tienopirimidinas Download PDF

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Publication number
ES2591129T3
ES2591129T3 ES13725935.4T ES13725935T ES2591129T3 ES 2591129 T3 ES2591129 T3 ES 2591129T3 ES 13725935 T ES13725935 T ES 13725935T ES 2591129 T3 ES2591129 T3 ES 2591129T3
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alkyl
nr6r7
group
cycloalkyl
alkoxy
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Georg Kettschau
Florian PÜHLER
Knut Eis
Ulrich Klar
Dirk Kosemund
Detlev Sülzle
Philip Lienau
Andrea HÄGEBARTH
Ulf Bömer
Lars Wortmann
Keith Graham
Antje Margret Wengner
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Bayer Pharma AG
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Bayer Pharma AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Immunology (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Un compuesto de fórmula general (I): **Fórmula** en la que: R1 representa un grupo seleccionado de: -C(>=O)O-R3, -C(>=O)N(H)R3, -C(>=O)NR3R4; R2a, R2b, R2c, R2d representan, independientemente entre sí, un átomo de hidrógeno o un grupo seleccionado de: alquil C1-C3-, alcoxi C1-C3-, halo-, hidroxi-, haloalquil C1-C3-, haloalcoxi C1-C3-, ciano-, -N(H)R5, -NR5R4; R3 representa un átomo de hidrógeno o un grupo seleccionado de: alquil C1-C6-, alquenil C2-C6-, alquinil C2-C6-, -(CH2)q-(cicloalquilo C3-C7), -(CH2)q-O-(cicloalquilo C3-C7), -(CH2)q-(cicloalquenilo C4-C7), -(CH2)q-O- (cicloalquenilo C4-C7), -(CH2)q-(heterocicloalquilo de 3 a 10 miembros), -(CH2)q-O-(heterocicloalquilo de 3 a 10 miembros), -(CH2)q-(heterocicloalquenilo de 4 a 10 miembros), -(CH2)q-O-(heterocicloalquenilo de 4 a 10 miembros), -(CH2)q-arilo, -(CH2)q-O-arilo, -(CH2)q-heteroarilo, -(CH2)q-O-heteroarilo; estando dicho grupo opcionalmente sustituido, una o más veces, de forma idéntica o diferente, con un sustituyente seleccionado de: halo-, hidroxi-, oxo- (O>=), ciano-, nitro-, alquil C1-C6-, alquenil C2-C6-, alquinil C2-C6-, haloalquil C1-C6-, alcoxi C1-C6-, haloalcoxi C1-C6-, hidroxialquil C1-C6-, alcoxi C1-C6-alquil C1-C6-, -(CH2)q-arilo, -(CH2)q-heteroarilo, -(CH2)q-(cicloalquilo C3-C7), -(CH2)q-(heterocicloalquilo de 3 a 10 miembros), haloalcoxi C1-C6-alquil C1-C6-, R5-O- , -C(>=O)R5, -C(>=O)O-R5, -OC(>=O)R5, -N(H)C(>=O)R5, -N(R4)C(>=O)R5, -N(H)C(>=O)NR5R4, -N(R4)C(>=O)NR5R4, -N(H)R5, -NR5R4, -C(>=O)N(H)R5, -C(>=O)NR5R4, R4-S-, R4-S(>=O), R4-S(>=O)2, -N(H)S(>=O)R4, -N(R4)S(>=O)R4, -S(>=O)N(H)R5, -S(>=O)NR5R4, -N(H)S(>=O)2R4, -N(R4)S(>=O)2R4, -S(>=O)2N(H)R5, -S(>=O)2NR5R4, -S(>=O)(>=NR5)R4, S(>=O)(>=NR4)R5, -N>=S(>=O)(R5)R4; o cuando dos sustituyentes están presentes en posición orto el uno con el otro en un anillo arilo o heteroarilo, dichos dos sustituyentes forman juntos un puente: *O(CH2)pO*, *NH(C(>=O))NH*, en los que * representa el punto de unión a dicho anillo arilo o heteroarilo; R4 representa un grupo seleccionado de: alquil C1-C6-, alquenil C2-C6-, alquinil C2-C6-, haloalquil C1-C6-, hidroxialquil C1-C6-, alcoxi C1-C6-alquil C1-C6-; o NR3R4 juntos representan un grupo heterocicloalquilo de 3 a 10 miembros o un heterocicloalquenilo de 4 a 10 miembros; que está opcionalmente sustituido, una o más veces, de forma idéntica o diferente, con halo-, hidroxi-, ciano-, nitro-, alquil C1-C6-, haloalquil C1-C6-, alcoxi C1-C6-, haloalcoxi C1-C6-, hidroxialquil C1-C6-, alcoxi C1-C6- alquil C1-C6-, R6R7N-alquil C1-C6-, haloalcoxi C1-C6-alquil C1-C6-, alquenil C2-C6-, alquinil C2-C6-, -(CH2)q-cicloalquilo C3-C7, -(CH2)q-arilo, -(CH2)q-heteroarilo, R5-O-, -C(>=O)R5, -C(>=O)O-R5, -OC(>=O)R5, -N(H)C(>=O)R5, -N(R4)C(>=O)R5, -N(H)C(>=O)NR6R7, -N(R5)C(>=O)NR6R7, -N(H)R5, -NR6R7, -C(>=O)N(H)R5, -C(>=O)NR6R7, R5-S-, R5-S(>=O), R5-S(>=O)2, -N(H)S(>=O)R5, -N(R5)S(>=O)R6, -S(>=O)N(H)R5, -S(>=O)NR6R7, -N(H)S(>=O)2R5, -N(R5)S(>=O)2R6, -S(>=O)2N(H)R6, -S(>=O)2NR6R7, -S(>=O)(>=NR5)R6, S(>=O)(>=NR5)R6, -N>=S(>=O)(R5)R6; en el que dichos grupos alquil C1-C6-, -(CH2)q-cicloalquilo C3-C7, -(CH2)q-arilo o -(CH2)q-heteroarilo están opcionalmente sustituidos, una o más veces, de forma idéntica o diferente, con halo-, hidroxi-, oxo- (O>=), ciano-, nitro-, alquil C1-C6-, haloalquil C1-C6-, alcoxi C1-C6-, haloalcoxi C1-C6-, hidroxialquil C1-C6-, alcoxi C1-C6-alquil C1-C6-, R6R7N-alquil C1-C6-, haloalcoxi C1-C6-alquil C1-C6-, alquenil C2-C6-, alquinil C2-C6-, R5-O-, -C(>=O)R5, -C(>=O)-R5, -OC(>=O)R5, -N(H)C(>=O)R5, -N(R4)C(>=O)R5, -N(H)C(>=O)NR6R7, -N(R5)C(>=O)NR6R7, -N(H)R5, -NR6R7, -C(>=O)N(H)R5, -C(>=O)NR6R7, R5-S-, R5-S(>=O), R5-S(>=O)2, -N(H)S(>=O)R5, -N(R5)S(>=O)R6, -S(>=O)N(H)R5, -S(>=O)NR5R6, -N(H)S(>=O)2R5, -N(R5)S(>=O)2R6, -S(>=O)2N(H)R6, -S(>=O)2NR5R6, -S(>=O)(>=NR5)R6, S(>=O)(>=NR5)R6, -N>=S(>=O)(R5)R6; R5 representa un átomo de hidrógeno, un grupo alquil C1-C6- o un cicloalquil C3-C7-; R6 representa un átomo de hidrógeno, un grupo alquil C1-C6- o un cicloalquil C3-C7-; R7 representa un átomo de hidrógeno, un grupo alquil C1-C6- o un cicloalquil C3-C7-; o NR6R7 juntos representan un grupo heterocicloalquilo de 3 a 10 miembros o un heterocicloalquenilo de 4 a 10 miembros; p representa un número entero de 1 o 2; q representa un número entero de 0, 1, 2 o 3; o un tautómero, un N-óxido, un hidrato, un solvato o una sal farmacéuticamente aceptable del mismo, o una mezcla del mismo.
ES13725935.4T 2012-05-21 2013-05-17 Tienopirimidinas Active ES2591129T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP12168670 2012-05-21
EP12168670 2012-05-21
EP13153607 2013-02-01
EP13153607 2013-02-01
PCT/EP2013/060233 WO2013174744A1 (en) 2012-05-21 2013-05-17 Thienopyrimidines

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US (1) US9540392B2 (es)
EP (1) EP2852596B1 (es)
JP (1) JP6234444B2 (es)
CN (1) CN104507950B (es)
AR (1) AR091093A1 (es)
CA (1) CA2873975A1 (es)
ES (1) ES2591129T3 (es)
HK (1) HK1206723A1 (es)
UY (1) UY34817A (es)
WO (1) WO2013174744A1 (es)

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CN105377845B (zh) 2013-02-01 2017-11-24 拜耳制药股份公司 取代的吡唑并嘧啶基氨基‑吲唑类
CN105308054B (zh) 2013-03-06 2017-11-21 拜耳制药股份公司 取代的噻唑并嘧啶

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US9540392B2 (en) 2017-01-10
UY34817A (es) 2013-12-31
WO2013174744A1 (en) 2013-11-28
AR091093A1 (es) 2015-01-14
CN104507950B (zh) 2017-03-22
HK1206723A1 (en) 2016-01-15
CN104507950A (zh) 2015-04-08
JP2015517545A (ja) 2015-06-22
US20150133425A1 (en) 2015-05-14
EP2852596A1 (en) 2015-04-01
EP2852596B1 (en) 2016-06-22
CA2873975A1 (en) 2013-11-28
JP6234444B2 (ja) 2017-11-22

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