JP2000509388A - 抗炎症薬剤として有用なステロイドナイトレートエステル誘導体を含有する新規医薬組成物 - Google Patents
抗炎症薬剤として有用なステロイドナイトレートエステル誘導体を含有する新規医薬組成物Info
- Publication number
- JP2000509388A JP2000509388A JP9538947A JP53894797A JP2000509388A JP 2000509388 A JP2000509388 A JP 2000509388A JP 9538947 A JP9538947 A JP 9538947A JP 53894797 A JP53894797 A JP 53894797A JP 2000509388 A JP2000509388 A JP 2000509388A
- Authority
- JP
- Japan
- Prior art keywords
- group
- carbon atoms
- hydrogen
- lower alkyl
- hydroxy
- 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.)
- Ceased
Links
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Classifications
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- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 式: 式中、 点線は、単結合または二重結合を示し; R1は水素、ヒドロキシ、ナイトレートエステル(ONO2)、ハロゲン、ハロ アルキル、ニトロキシアルカノイル、チオール、ヘテロシクリック、低級アルコ キシ、アルキルシリルオキシ、低級アルキルからなる群から選ばれ、前記基のす べてはヒドロキシ、ハロゲン、低級アルキル、低級アルケニル、低級アルキニル 、低級アルコキシ、アミノ、ニトロ、ニトリル、カルボキシルおよびハロアルキ ル基で任意に置換することができ、あるいは R1は式OCO−R7(式中、R7はアルカン酸、低級アルキル、低級アルケニ ル、低級アルキニル、または低級アルコキシである)を有する基であり; R2はナイトレートエステル(ONO2)であり; R3およびR4は、それぞれ水素、ヒドロキシ、ナイトレートエステル(ONO2 )、ニトロキシアルカイル、低級アルキル、低級アルケニル、低級アルキニル および低級アルコキシからなる群から選ばれ、前記基のすべてはヒドロキシ、低 級アルキル、低級アルケニル、低級アルキニル、低級アルコキシ、アミノ、ニト ロ、ニトリル、カルボキシルおよびハロアルキル基で任意に置換することができ 、あるいは R3およびR4は、それぞれ式OCO−R8(式中、R8は2−フラニル、低級ア ルキルまたは低級アルコキシ基である)を有する基から選ばれ、あるいは R3およびR4は、任意に式: (式中、KおよびLは水素および低級アルキルからなる群から選ばれる、ある いは任意にKおよびLは脂環式環または複素環式環を形成できる) を有する環状構造を形成することがあり; R5は水素またはハロゲンであり; R6は水素、ヒドロキシ、または酸素であり; PおよびQは、それぞれ水素、クロロ、フルオロおよび低級アルキルからなる 群から選ばれ;そして Xは、もしR1がハロアルキルであれば、低級アルキルまたは硫黄である、 を有する化合物ならびにその製薬上容認しうるエステルおよびプロドラッグを、 製薬上容認しうる担体と共に含有してなる医薬品組成物。 2. 式1中、点線は単結合または二重結合を示し; R1は水素、ヒドロキシ、ナイトレートエステル(ONO2)、ハロゲン、2か ら5炭素原子と1から2ヘテロ原子を有する複素環基、2から約6炭素原子のニ トロキシアルカノイル基、チオール、1から約6炭素原子のハロアルキル基、1 から約6炭素原子の低級アルコキシ基、3から約8炭素原子のアルキルシリルオ キシ基、1から約6炭素原子の低級アルキル基からなる群から選ばれ、そして前 記基のすべては任意にヒドロキシ、ハロゲン、低級アルキル、低級アルケニル、 低級アルキニル、低級アルコキシ、アミノ、ニトロ、ニトリル、カルボキシルお よびハロアルキル基で置換することができ;あるいは R1は式OCO−R7(式中、R7は2から約6炭素原子のアルカン酸基、1か ら約6炭素原子の低級アルキル基、2から約6炭素原子の低級アルケニル基、2 から約6炭素原子の低級アルキニル基、または1から約6炭素原子の低級アル コキシ基である)を有する基であり; R2はナイトレートエステル(ONO2)であり; R3およびR4は、それぞれ水素、ヒドロキシ、ナイトレートエステル(ONO2 )、2から約6炭素原子のニトロキシアルカノイル基、1から約6炭素原子の 低級アルキル基、2から約6炭素原子の低級アルケニル基、2から約6炭素原子 の低級アルキニル基、1から約6炭素原子の低級アルコキシ基からなる群から選 ばれ、そして前記基のすべては任意にヒドロキシ、低級アルキル、低級アルケニ ル、低級アルキニル、低級アルコキシ、アミノ、ニトロ、ニトリル、カルボキシ ルおよびハロアルキル基で置換することができ、あるいは R3およびR4は、それぞれ式OCO−R8(式中、R8は2−フラニル、1から 約6炭素原子の低級アルキル基または1から約6炭素原子の低級アルコキシ基で ある)を有する基から選ばれ;あるいは R3およびR4は、任意に式: (式中、KおよびLは、水素、1から約8炭素原子の低級アルキル基からなる 群から選ばれ、またKおよびLは、任意に4から約8炭素原子の脂環式環または 4−6炭素原子と窒素、酸素または硫黄から選ばれる1−2ヘテロ原子とを有す る複素環式環を形成できる) を有する環状構造を形成することができ、 R5は水素またはハロゲンであり; R6は水素、ヒドロキシまたは酸素であり; PおよびQは、それぞれ水素、クロロ、フルオロおよび1から6炭素原子の低 級アルキル基からなる群から選ばれ;そして Xは、もしR1がハロアルキルであれば、低級アルキル基または硫黄である、 化合物を、製薬上容認しうる担体と共に含有してなる、請求項1記載の医薬品組 成物。 3. 式1中、点線は単結合または二重結合を示し; R1は水素、ヒドロキシ、ナイトレートエステル(ONO2)、ハロゲン、チオ ール、3から4炭素原子と1から2ヘテロ原子とを有する複素環式基、2から約 4炭素原子のニトロキシアルカノイル基、1から約4炭素原子の低級アルコキシ 基、1から約4炭素原子の低級アルキル基からなる群から選ばれ、そして前記基 のすべては任意にヒドロキシ、クロロ、フルオロ、低級アルキル、低級アルケニ ル、低級アルキニル、低級アルコキシ、アミノ、ニトロ、ニトリル、カルボキシ ルおよびハロアルキル基で置換することができ;あるいは R1は式OCO−R7(式中、R7は2から約4炭素原子のアルカン酸基、1か ら約4炭素原子の低級アルキル基、2から約4炭素原子の低級アルケニル基、2 から約4炭素原子の低級アルキニル基または1から約4炭素原子の低級アルコキ シ基である)を有する基であり; R2はナイトレートエステル(ONO2)であり; R3およびR4は、それぞれ水素、ヒドロキシ、ナイトレートエステル(ONO2 )、2から約4炭素原子のニトロキシアルカノイル基、1から約4炭素原子の 低級アルキル基、2から約4炭素原子の低級アルケニル基、2から約4炭素原子 の低級アルキニル基、1から約4炭素原子の低級アルコキシ基からなる群から選 ばれ、そして前記基のすべてはヒドロキシ、低級アルキル、低級アルケニル、低 級アルキニル、低級アルコキシ、アミノ、ニトロ、およびハロアルキル基で任意 に置換することができ、あるいは R3およびR4は、式OCO−R8(式中、R8は2−フラニル、1から約4炭素 原子の低級アルキル基または1から約4炭素原子の低級アルコキシ基である)を 有する基であり;あるいは R3およびR4は一緒に結合して任意に式: (式中、KおよびLは水素および1から約6炭素原子の低級アルキル基からな る群から選ばれ;任意にKおよびLは5−8炭素原子の脂環式環、または4−5 炭素原子と窒素、酸素または硫黄から選ばれる1−2ヘテロ原子との複素環式環 を形成できる) を有する環状構造を形成することがあり; R5は水素またはハロゲンであり; R6は水素、ヒドロキシ、または酸素であり; PおよびQはそれぞれ水素、クロロ、フルオロおよび1から4炭素原子の低級 アルキル基からなる群から選ばれ;そして Xは、もしR1がハロアルキルであれば、メチレンまたは硫黄である、 化合物を、製薬上容認しうる担体と共に含有してなる、請求項1記載の医薬品組 成物。 4. 式1中、点線は単結合または二重結合を示し; R1は水素、ヒドロキシ、ナイトレートエステル(ONO2)、クロロ、チオー ル、1から4炭素原子の低級アルキル基からなる群から選ばれ;あるいは R1は式OCO−R7(式中、R7はプロパン酸、メチルまたはエチルである) を有する基であり; R2はナイトレートエステル(ONO2)であり; R3およびR4は、それぞれ水素、ヒドロキシ、ナイトレートエステル(ONO2 )、メチル、2から4炭素原子の低級アルキニル基からなる群から選ばれ;あ るいは R3およびR4は式OCO−R8(式中、R8はエトキシ、2−フラニル、メチル 、エチル、プロピルまたはブチルである)を有する基であり;あるいは R3およびR4は一緒に結合して任意に式: (式中、KおよびLは水素、メチルおよびブチルからなる群から選ばれ;ある いはKおよびLは任意にシクロペンチルまたはシクロヘキシル環を形成しうる) を有する環状構造を形成することができ; R5は水素、クロロまたはブロモであり; R6はヒドロキシまたは酸素であり; PおよびQは、それぞれ水素、クロロ、フルオロおよびメチルから選ばれ;そ して Xはメチレンである、 化合物を、製薬上容認しうる担体と共に含有してなる、請求項1記載の医薬品組 成物。 5. 請求項1、請求項2、請求項3または請求項4記載の医薬品組成物の治療 上有効な量を投与することにより、炎症をもつ患者を治療する方法。 6. 請求項1、請求項2、請求項3または請求項4記載の医薬品組成物の治療 上有効な量を投与することにより、望まない平滑筋収縮をもつ患者を治療する方 法。 7. 請求項1、請求項2、請求項3または請求項4記載の医薬品組成物の治療 上有効な量を投与することにより、望まない平滑筋収縮および炎症をもつ患者を 治療する方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/642,128 | 1996-05-02 | ||
US08/642,128 US5985862A (en) | 1996-05-02 | 1996-05-02 | Pharmaceutical compositions having steroid nitrate ester derivatives useful as anti-inflammatory drugs |
PCT/US1997/006374 WO1997040836A1 (en) | 1996-05-02 | 1997-04-28 | Novel pharmaceutical compositions having steroid nitrate ester derivatives useful as anti-inflammatory drugs |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2000509388A true JP2000509388A (ja) | 2000-07-25 |
Family
ID=24575322
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP9538947A Ceased JP2000509388A (ja) | 1996-05-02 | 1997-04-28 | 抗炎症薬剤として有用なステロイドナイトレートエステル誘導体を含有する新規医薬組成物 |
Country Status (11)
Country | Link |
---|---|
US (1) | US5985862A (ja) |
EP (1) | EP0912185B1 (ja) |
JP (1) | JP2000509388A (ja) |
AT (1) | ATE237334T1 (ja) |
AU (1) | AU2732597A (ja) |
CA (1) | CA2252876A1 (ja) |
DE (1) | DE69720996T2 (ja) |
DK (1) | DK0912185T3 (ja) |
ES (1) | ES2197341T3 (ja) |
PT (1) | PT912185E (ja) |
WO (1) | WO1997040836A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011529461A (ja) * | 2008-07-31 | 2011-12-08 | ニコックス エス エイ | 21位の芳香族リンカーを介して硝酸エステルに結合したグルココルチコイド類および眼科におけるそれらの使用 |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5824669A (en) | 1996-03-22 | 1998-10-20 | Nitromed, Inc. | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
IT1285770B1 (it) | 1996-10-04 | 1998-06-18 | Nicox Sa | Composti corticoidei |
WO2000049993A2 (en) * | 1999-02-24 | 2000-08-31 | Nitromed, Inc. | Nitrosated and nitrosylated steroids for the treatment of cardiovascular diseases and disorders |
IT1311922B1 (it) * | 1999-04-13 | 2002-03-20 | Nicox Sa | Composti farmaceutici. |
US6777399B2 (en) | 2000-08-05 | 2004-08-17 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
BRPI0113042B8 (pt) | 2000-08-05 | 2021-05-25 | Glaxo Group Ltd | composto da fórmula ou um seu solvato fisiologicamente aceitável, uso do mesmo, composição farmacêutica, formulação farmacêutica, método para o tratamento de um indivíduo humano ou animal com uma condição inflamatória e/ou alérgica, e, processo para preparar um composto ou um seu solvato |
GB0019172D0 (en) | 2000-08-05 | 2000-09-27 | Glaxo Group Ltd | Novel compounds |
IT1320176B1 (it) * | 2000-12-22 | 2003-11-26 | Nicox Sa | Dispersioni solide di principi attivi nitrati. |
US6696592B2 (en) | 2001-05-22 | 2004-02-24 | Nicox-S.A. | Methods of making 21-[4′-(nitrooxyalkyl)benzoate] corticosteroid derivatives and intermediates useful in the synthesis thereof |
US20040110691A1 (en) * | 2001-11-13 | 2004-06-10 | Stamler Jonathan S. | Thiol reactive agents as a therapeutic modality |
US6627602B2 (en) * | 2001-11-13 | 2003-09-30 | Duke University | Preventing desensitization of receptors |
EP1336602A1 (en) * | 2002-02-13 | 2003-08-20 | Giovanni Scaramuzzino | Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases |
GB2389530B (en) | 2002-06-14 | 2007-01-10 | Cipla Ltd | Pharmaceutical compositions |
US20060247216A1 (en) * | 2002-10-25 | 2006-11-02 | Haj-Yehia Abdullah I | Steroid compounds comprising superoxide dismutase mimic groups and nitric oxide donor groups, and their use in the preparation of medicaments |
SE0300971D0 (sv) * | 2003-04-03 | 2003-04-03 | Aga Ab | Nitric oxide in treatment of inflammation |
US8226987B2 (en) * | 2005-02-22 | 2012-07-24 | Zoorob George K | Herbal preparation to relieve inflammation and smooth muscle contraction |
AU2006286838C1 (en) * | 2005-09-02 | 2013-05-02 | Ferrer Internacional S.A. | Nitrooxy derivatives of glucocorticoids |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1082573A (en) * | 1965-02-12 | 1967-09-06 | Boots Pure Drug Co Ltd | Improvements in the preparation of steroid esters |
US3639434A (en) * | 1967-02-02 | 1972-02-01 | Boots Pure Drug Co Ltd | 17-acyloxysteroids and their manufacture |
HU164115B (ja) * | 1971-05-07 | 1973-12-28 | ||
DE2236115A1 (de) * | 1972-07-20 | 1974-02-07 | Schering Ag | Verfahren zur herstellung von delta hoch 4.9(11).16 -3.20diketosteroiden |
DE4223800A1 (de) * | 1992-07-20 | 1994-01-27 | Cassella Farbwerke Mainkur Ag | Verwendung von 1.2.5-Oxadiazol-2-oxiden zur Behandlung erektiler Dysfunktionen |
ES2125342T3 (es) * | 1992-07-30 | 1999-03-01 | Cal Int Ltd | Esteres y combinaciones de un nitrato organico y de un salicilato. |
IT1256450B (it) * | 1992-11-26 | 1995-12-05 | Soldato Piero Del | Esteri nitrici con attivita' farmacologica e procedimento per la loro preparazione |
HU218923B (hu) * | 1993-10-06 | 2000-12-28 | Nicox S.A. | Gyulladásgátló és/vagy fájdalomcsillapító hatású nitrát-észterek, ezeket tartalmazó gyógyszerkészítmények és eljárás a vegyületek előállítására |
-
1996
- 1996-05-02 US US08/642,128 patent/US5985862A/en not_active Expired - Fee Related
-
1997
- 1997-04-28 WO PCT/US1997/006374 patent/WO1997040836A1/en active IP Right Grant
- 1997-04-28 DE DE69720996T patent/DE69720996T2/de not_active Expired - Fee Related
- 1997-04-28 PT PT97921224T patent/PT912185E/pt unknown
- 1997-04-28 ES ES97921224T patent/ES2197341T3/es not_active Expired - Lifetime
- 1997-04-28 DK DK97921224T patent/DK0912185T3/da active
- 1997-04-28 CA CA002252876A patent/CA2252876A1/en not_active Abandoned
- 1997-04-28 AT AT97921224T patent/ATE237334T1/de not_active IP Right Cessation
- 1997-04-28 EP EP97921224A patent/EP0912185B1/en not_active Expired - Lifetime
- 1997-04-28 JP JP9538947A patent/JP2000509388A/ja not_active Ceased
- 1997-04-28 AU AU27325/97A patent/AU2732597A/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011529461A (ja) * | 2008-07-31 | 2011-12-08 | ニコックス エス エイ | 21位の芳香族リンカーを介して硝酸エステルに結合したグルココルチコイド類および眼科におけるそれらの使用 |
Also Published As
Publication number | Publication date |
---|---|
WO1997040836A1 (en) | 1997-11-06 |
PT912185E (pt) | 2003-08-29 |
CA2252876A1 (en) | 1997-11-06 |
EP0912185B1 (en) | 2003-04-16 |
ES2197341T3 (es) | 2004-01-01 |
DK0912185T3 (da) | 2003-08-04 |
EP0912185A1 (en) | 1999-05-06 |
DE69720996D1 (de) | 2003-05-22 |
AU2732597A (en) | 1997-11-19 |
DE69720996T2 (de) | 2004-02-05 |
US5985862A (en) | 1999-11-16 |
ATE237334T1 (de) | 2003-05-15 |
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