JPS6145970B2 - - Google Patents
Info
- Publication number
- JPS6145970B2 JPS6145970B2 JP55159667A JP15966780A JPS6145970B2 JP S6145970 B2 JPS6145970 B2 JP S6145970B2 JP 55159667 A JP55159667 A JP 55159667A JP 15966780 A JP15966780 A JP 15966780A JP S6145970 B2 JPS6145970 B2 JP S6145970B2
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- chloro
- methyl
- formula
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000000203 mixture Substances 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 7
- 229920000742 Cotton Polymers 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 206010018691 Granuloma Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- -1 steroid compounds Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は医薬組成物殊にステロイド化合物に見
られる副作用が著しく軽減され価値ある薬理的性
質を有し、炎症疾患を治療するため有用な医薬組
成物に関する。
西独国特許公開明細書第2741067号、特に実施
例２、３には、それぞれ９α−クロル−６α−フ
ルオロ−11β・17・21−トリヒドロキシ−16α−
メチル−１・４−プレグナジエン−３・20−ジオ
ン−17・21−ジアセテート及び９α−クロル−６
α−フルオロ−11β・17・21−トリヒドロキシ−
16α−メチル−１・４−プレグナジエン−３・20
−ジオン−21−バレレートがそれら例の目的化合
物の製造原料として記載されており、また特開昭
52−89662号には既に９α・21−ジハロゲノ−11
β・17α−ジヒドロキシ−６α−フルオロ−16α
−メチル−プレグナ−１・４−ジエン−３・20−
ジオン化合物が抗炎症作用を有することが記載さ
れている。
本発明は、式（）：
式中、R1はメチル又はエチル基、そして、R2
はC1−４のアルキル基、またはフエニール基を
意味する、で示される少なくとも１つの６α−フ
ルオロ−９α−クロロ−16β−メチル−プレドニ
ゾロンの17・21−ジエステルの有効量を含有する
ことを特徴とする炎症状態の治療に有用な組成物
に関する。
式（）で示される組成物のうち、殊に価値の
あるものは、次の化合物である（参照番号を付し
た）。
(121) ６α−フルオロ−９α−クロロ−16β−
メチルプレドニゾロン−17・21−ジアセテート
(122) ６α−フルオロ−９α−クロロ−16β−
メチルプレドニゾロン−17・21−ジプロピオネ
ート
(123) ６α−フルオロ−９α−クロロ−16β−
メチルプレドニゾロン−17−バレレート−21−
アセテート
(124) ６α−フルオロ−９α−クロロ−16β−
メチルプレドニゾロン−17−ベンゾエート−21
−アセテート
(125) ６α−フルオロ−９α−クロロ−16β−
メチルプレドニゾロン−17−プロピオネート、
21−アセテート
生物学的活性
コツトンペレツト肉芽腫法を用いて、本発明の
化合物の生物学的活性をベクロメサゾンジプロピ
オネート（Beclomethasone dipropinate）と比
較した。体重約135ｇのSpraque−Dawley種の雌
ラツトを用い、各動物に、麻酔下10mgのコツトン
ペレツトを皮下に植えこんだ。コツトンペレツト
は予め実験組成物の25ml溶液及び２％のカラゲニ
ン懸濁液50mlに浸漬したのち、乾燥させておい
た。コツトンペレツトは、試験化合物をそれぞれ
0.1、又は10mgを含む（各化合物の各濃度につき
それぞれ10匹を用いた）。７日後、ラツトを屠殺
し、コツトンペレツトのまわりにできた肉芽腫を
除き、80℃で乾燥したのち、秤量した。副腎及び
胸腺も取つて秤量した。
同じ操作をベクロメサゾンジプロピオネート及
びコントロールについて繰り返した。
結果を第１表に示す。表中、化合物は参照番号
で示されている。
The present invention relates to pharmaceutical compositions, particularly pharmaceutical compositions that have valuable pharmacological properties that significantly reduce the side effects seen with steroid compounds and are useful for treating inflammatory diseases. West German Patent Application No. 2741067, in particular Examples 2 and 3, each contain 9α-chloro-6α-fluoro-11β·17·21-trihydroxy-16α-
Methyl-1,4-pregnadiene-3,20-dione-17,21-diacetate and 9α-chloro-6
α-Fluoro-11β・17・21-trihydroxy-
16α-methyl-1,4-pregnadiene-3,20
-dione-21-valerate is described as a raw material for the production of the target compounds in these examples, and
No. 52-89662 already contains 9α・21-dihalogeno-11
β・17α-dihydroxy-6α-fluoro-16α
-Methyl-pregna-1,4-diene-3,20-
It has been described that dione compounds have anti-inflammatory effects. The present invention is based on the formula (): In the formula, R 1 is a methyl or ethyl group, and R 2
means a C1-4 alkyl group or a phenyl group, and is characterized by containing an effective amount of at least one 17,21-diester of 6α-fluoro-9α-chloro-16β-methyl-prednisolone represented by The present invention relates to compositions useful for treating inflammatory conditions. Of particular value among the compositions of formula () are the following compounds (designated with reference numbers): (121) 6α-fluoro-9α-chloro-16β-
Methylprednisolone-17・21-diacetate (122) 6α-fluoro-9α-chloro-16β-
Methylprednisolone-17・21-dipropionate (123) 6α-fluoro-9α-chloro-16β-
Methylprednisolone-17-valerate-21-
Acetate (124) 6α-fluoro-9α-chloro-16β-
Methylprednisolone-17-benzoate-21
-acetate (125) 6α-fluoro-9α-chloro-16β-
Methylprednisolone-17-propionate,
21-Acetate Biological Activity The biological activity of the compounds of the invention was compared to Beclomethasone dipropinate using the Cotton pellet granuloma method. Female Spraque-Dawley rats weighing approximately 135 g were used and each animal was subcutaneously implanted with 10 mg of cotton pellets under anesthesia. The cotton pellets were previously soaked in 25 ml of a solution of the experimental composition and 50 ml of a 2% carrageenan suspension, and then dried. Cotton pellets contain each test compound.
0.1 or 10 mg (10 animals were used for each concentration of each compound). After 7 days, the rats were sacrificed, granulomas formed around the cotton pellets were removed, dried at 80°C, and weighed. The adrenal glands and thymus were also removed and weighed. The same operation was repeated for beclomethasone dipropionate and control. The results are shown in Table 1. In the table, compounds are indicated by reference numbers.
【表】
ピオネート
10 〓55.0 〓1.7 〓4.7
[Table] Pionate
10 〓55.0 〓1.7 〓4.7
Claims (1)
はC1−４のアルキル基、またはフエニール基を
意味する、で示される少なくとも１つの６α−フ
ルオロ−９α−クロロ−16β−メチル−プレドニ
ゾロンの17・21−ジエステルの有効量を含有する
ことを特徴とする消炎組成物。[Claims] 1 Formula (): In the formula, R 1 is a methyl or ethyl group, and R 2
means a C1-4 alkyl group or a phenyl group, and is characterized by containing an effective amount of at least one 17,21-diester of 6α-fluoro-9α-chloro-16β-methyl-prednisolone represented by anti-inflammatory composition.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT7927353A IT1209140B (en) | 1979-11-16 | 1979-11-16 | 6 ALFA-FLUORO-PREDNISOLONE 17,21-DIESTERI. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5683499A JPS5683499A (en) | 1981-07-08 |
| JPS6145970B2 true JPS6145970B2 (en) | 1986-10-11 |
Family
ID=11221485
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15966880A Pending JPS5695200A (en) | 1979-11-16 | 1980-11-14 | Novel 17*211diesters of 6alpha* 9alphaa difluoroo166methylpredonisolone |
| JP15966780A Granted JPS5683499A (en) | 1979-11-16 | 1980-11-14 | Novel 17*211diesters of 6 alphaafluoroo 9 alphaachloropredonizolone |
| JP15966680A Pending JPS5683498A (en) | 1979-11-16 | 1980-11-14 | Novel 17*211diesters of 6 alphaafluoropredonizolone |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15966880A Pending JPS5695200A (en) | 1979-11-16 | 1980-11-14 | Novel 17*211diesters of 6alpha* 9alphaa difluoroo166methylpredonisolone |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15966680A Pending JPS5683498A (en) | 1979-11-16 | 1980-11-14 | Novel 17*211diesters of 6 alphaafluoropredonizolone |
Country Status (3)
| Country | Link |
|---|---|
| JP (3) | JPS5695200A (en) |
| IT (1) | IT1209140B (en) |
| ZA (3) | ZA807085B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5289662A (en) * | 1975-12-12 | 1977-07-27 | Ciba Geigy Ag | Novel polyhalogenoosteroid and preparation thereof |
| DE2741067A1 (en) * | 1976-09-16 | 1978-03-23 | Ciba Geigy Ag | METHOD FOR PRODUCING 9,11-HALOGENATED STEROIDS |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4172075A (en) * | 1976-07-13 | 1979-10-23 | Ciba-Geigy Corporation | Fluoro-steroids and processes for their manufacture |
| JPS5331156A (en) * | 1976-09-03 | 1978-03-24 | Asahi Dow Ltd | Infrared thickness meter |
-
1979
- 1979-11-16 IT IT7927353A patent/IT1209140B/en active
-
1980
- 1980-11-14 JP JP15966880A patent/JPS5695200A/en active Pending
- 1980-11-14 JP JP15966780A patent/JPS5683499A/en active Granted
- 1980-11-14 JP JP15966680A patent/JPS5683498A/en active Pending
- 1980-11-14 ZA ZA00807085A patent/ZA807085B/en unknown
- 1980-11-14 ZA ZA00807086A patent/ZA807086B/en unknown
- 1980-11-14 ZA ZA00807088A patent/ZA807088B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5289662A (en) * | 1975-12-12 | 1977-07-27 | Ciba Geigy Ag | Novel polyhalogenoosteroid and preparation thereof |
| DE2741067A1 (en) * | 1976-09-16 | 1978-03-23 | Ciba Geigy Ag | METHOD FOR PRODUCING 9,11-HALOGENATED STEROIDS |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5683499A (en) | 1981-07-08 |
| ZA807088B (en) | 1981-10-28 |
| IT7927353A0 (en) | 1979-11-16 |
| ZA807085B (en) | 1981-10-28 |
| JPS5683498A (en) | 1981-07-08 |
| IT1209140B (en) | 1989-07-10 |
| JPS5695200A (en) | 1981-08-01 |
| ZA807086B (en) | 1981-10-28 |
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