PL198434B1 - Nowe mostkowane indenopirolokarbazole, kompozycje farmaceutyczne zawierające te związki i ich zastosowanie - Google Patents
Nowe mostkowane indenopirolokarbazole, kompozycje farmaceutyczne zawierające te związki i ich zastosowanieInfo
- Publication number
- PL198434B1 PL198434B1 PL344475A PL34447599A PL198434B1 PL 198434 B1 PL198434 B1 PL 198434B1 PL 344475 A PL344475 A PL 344475A PL 34447599 A PL34447599 A PL 34447599A PL 198434 B1 PL198434 B1 PL 198434B1
- Authority
- PL
- Poland
- Prior art keywords
- compound
- formula
- tie
- alkyl
- iii
- Prior art date
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- 230000002105 relative biological effectiveness Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
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- 235000021309 simple sugar Nutrition 0.000 description 1
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- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
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- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
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- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
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- Reproductive Health (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8811498P | 1998-06-05 | 1998-06-05 | |
| US09/325,140 US6127401A (en) | 1998-06-05 | 1999-06-03 | Bridged indenopyrrolocarbazoles |
| PCT/US1999/012531 WO1999062523A1 (en) | 1998-06-05 | 1999-06-04 | Bridged indenopyrrolocarbazoles |
Publications (2)
| Publication Number | Publication Date |
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| PL344475A1 PL344475A1 (en) | 2001-11-05 |
| PL198434B1 true PL198434B1 (pl) | 2008-06-30 |
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| PL344475A PL198434B1 (pl) | 1998-06-05 | 1999-06-04 | Nowe mostkowane indenopirolokarbazole, kompozycje farmaceutyczne zawierające te związki i ich zastosowanie |
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| HU (1) | HUP0102512A3 (enExample) |
| NO (1) | NO20006166L (enExample) |
| NZ (1) | NZ508306A (enExample) |
| PL (1) | PL198434B1 (enExample) |
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| SK (1) | SK285368B6 (enExample) |
| TR (1) | TR200003623T2 (enExample) |
| UA (1) | UA66865C2 (enExample) |
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| US6811992B1 (en) * | 1998-05-14 | 2004-11-02 | Ya Fang Liu | Method for identifying MLK inhibitors for the treatment of neurological conditions |
| US6127401A (en) * | 1998-06-05 | 2000-10-03 | Cephalon, Inc. | Bridged indenopyrrolocarbazoles |
| HK1040053B (en) | 1998-09-25 | 2007-09-21 | Cephalon, Inc. | Use of fused pyrrolocarbazoles for preventing/treating damage to sensory hair cells and cochlear neurons |
| US6841567B1 (en) * | 1999-02-12 | 2005-01-11 | Cephalon, Inc. | Cyclic substituted fused pyrrolocarbazoles and isoindolones |
| US6630500B2 (en) | 2000-08-25 | 2003-10-07 | Cephalon, Inc. | Selected fused pyrrolocarbazoles |
| US20020169154A1 (en) * | 2001-04-04 | 2002-11-14 | Cephalon, Inc. | Novel methods and compositions involving trk tyrosine kinase inhibitors and antineoplastic agents |
| US7018999B2 (en) | 2001-05-16 | 2006-03-28 | Cephalon, Inc. | Methods for the treatment and prevention of pain |
| CA2398828A1 (en) * | 2002-08-09 | 2004-02-09 | Merck & Co., Inc. | A pharmaceutical composition containing an indolopyrrolocarbazole derivative |
| AU2003259846A1 (en) * | 2002-08-16 | 2004-03-03 | The General Hospital Corporation | Non-invasive functional imaging of peripheral nervous system activation in humans and animals |
| EP1545615A4 (en) * | 2002-10-04 | 2006-03-01 | Rinat Neuroscience Corp | METHODS OF TREATING CARDIAC ARRHYTHMIA AND PREVENTING DEATH OF CARDIAC ARRHYTHMIA USING NGF ANTAGONISTS |
| WO2004032870A2 (en) | 2002-10-08 | 2004-04-22 | Rinat Neuroscience Corp. | Methods for treating post-surgical pain by admisnistering a nerve growth factor antagonist and compositions containing the same |
| US7255860B2 (en) * | 2002-10-08 | 2007-08-14 | Rinat Neuroscience Corp. | Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist antibody |
| UA80447C2 (en) | 2002-10-08 | 2007-09-25 | Methods for treating pain by administering nerve growth factor antagonist and opioid analgesic | |
| US9498530B2 (en) | 2002-12-24 | 2016-11-22 | Rinat Neuroscience Corp. | Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same |
| US7569364B2 (en) * | 2002-12-24 | 2009-08-04 | Pfizer Inc. | Anti-NGF antibodies and methods using same |
| DK1575517T3 (da) * | 2002-12-24 | 2012-05-14 | Rinat Neuroscience Corp | Anti-ngf-antistoffer og fremgangsmåder til anvendelse af samme |
| KR20050111598A (ko) | 2003-02-19 | 2005-11-25 | 리나트 뉴로사이언스 코퍼레이션 | 신경 성장 인자 길항제 및 ｎｓａｉｄ를 투여함으로써통증을 치료하는 방법 및 그것을 함유하는 조성물 |
| US7241779B2 (en) * | 2003-12-23 | 2007-07-10 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| KR101637908B1 (ko) * | 2004-04-07 | 2016-07-11 | 리나트 뉴로사이언스 코프. | 신경성장인자 길항제의 투여에 의한 골암 통증의 치료방법 |
| US7419972B2 (en) * | 2004-07-02 | 2008-09-02 | Schering Ag | 2-substituted estra-1,3,5(10)-trien-17-ones as inhibitors of 17β-hydroxy steroid dehydrogenase type 1 |
| US20060058250A1 (en) * | 2004-09-10 | 2006-03-16 | Cephalon, Inc. | Methods of treating proliferative skin diseases using carbazole derivatives |
| US20080021013A1 (en) * | 2006-07-21 | 2008-01-24 | Cephalon, Inc. | JAK inhibitors for treatment of myeloproliferative disorders |
| KR101160225B1 (ko) | 2007-02-01 | 2012-07-11 | 페링 인터내셔널 센터 에스 에이 | 자궁 내막증 치료용 약제 |
| SA08290041B1 (ar) | 2007-02-01 | 2012-06-05 | فيرينج انترناشونال سنتر اس آيه | أدوية من أجل معالجة بطانة الرحم |
| EP1952813A1 (en) * | 2007-02-01 | 2008-08-06 | Ferring International Center S.A. | Medicament for the treatment of endometriosis |
| EP4514998A1 (en) | 2022-04-27 | 2025-03-05 | Regeneron Pharmaceuticals, Inc. | Treatment of arthropathy based upon stratification of osteoarthritis polygenic risk score |
| CN120752534A (zh) | 2023-03-17 | 2025-10-03 | 瑞泽恩制药公司 | 骨关节炎(oa)的蛋白质组学风险评分 |
| WO2026054762A1 (en) | 2024-09-05 | 2026-03-12 | Regeneron Pharmaceuticals, Inc. | Proteomic risk score for adjudicated arthropathy (aa) |
Family Cites Families (42)
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| JPS62220196A (ja) * | 1986-03-20 | 1987-09-28 | Kyowa Hakko Kogyo Co Ltd | 新規物質ｕｃｎ―０１ |
| US4816450A (en) * | 1986-09-15 | 1989-03-28 | Duke University | Inhibition of protein kinase C by long-chain bases |
| US4735939A (en) * | 1987-02-27 | 1988-04-05 | The Dow Chemical Company | Insecticidal activity of staurosporine |
| WO1988007045A1 (fr) * | 1987-03-09 | 1988-09-22 | Kyowa Hakko Kogyo Co., Ltd. | Derives de la substance physiologiquement active k-252 |
| JPH07113027B2 (ja) * | 1987-12-24 | 1995-12-06 | 協和醗酵工業株式会社 | Ｋ−２５２誘導体 |
| FR2631199B1 (fr) * | 1988-05-09 | 1991-03-15 | Centre Nat Rech Scient | Reacteur a plasma |
| US5668271A (en) * | 1991-11-29 | 1997-09-16 | Banyu Pharmaceutical Co., Ltd. | Indolopyrrolocarbazole derivatives |
| US5591842A (en) * | 1991-11-29 | 1997-01-07 | Banyu Pharmaceutical Co., Ltd. | Indolopyrrolocarbazole derivatives |
| US5437996A (en) * | 1992-11-24 | 1995-08-01 | Banyu Pharmaceutical Co., Ltd. | Microtetraspora strain for preparation of indolopyrrolocarbazole derivatives |
| US5589365A (en) * | 1991-11-29 | 1996-12-31 | Banyu Pharmaceutical Co., Ltd. | Process for producing glycosylated indolopyrrolocarbazole derivatives by culturing certain microorganisms |
| EP0575955B1 (en) * | 1992-06-22 | 1999-09-15 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing staurosporine derivatives |
| US5756494A (en) * | 1992-07-24 | 1998-05-26 | Cephalon, Inc. | Protein kinase inhibitors for treatment of neurological disorders |
| US5621101A (en) * | 1992-07-24 | 1997-04-15 | Cephalon, Inc. | Protein kinase inhibitors for treatment of neurological disorders |
| US5461146A (en) * | 1992-07-24 | 1995-10-24 | Cephalon, Inc. | Selected protein kinase inhibitors for the treatment of neurological disorders |
| US5621100A (en) * | 1992-07-24 | 1997-04-15 | Cephalon, Inc. | K-252a derivatives for treatment of neurological disorders |
| DE69331228T4 (de) * | 1992-09-21 | 2002-09-05 | Kyowa Hakko Kogyo Co., Ltd. | Heilmittel für thrombozytopenia |
| WO1994007895A1 (en) * | 1992-09-25 | 1994-04-14 | Schering Corporation | Diindolo compounds and pharmaceutical compositions containing them |
| US5721230A (en) * | 1993-05-10 | 1998-02-24 | Hoffmann-La Roche Inc. | Substituted pyrroles |
| WO1994027982A1 (en) * | 1993-05-28 | 1994-12-08 | Cephalon, Inc. | Use of indolocarbazole derivatives to treat a pathological condition of the prostate |
| US5468872A (en) * | 1993-09-16 | 1995-11-21 | Cephalon, Inc. | K-252a functional derivatives potentiate neurotrophin-3 for the treatment of neurological disorders |
| JPH07112987A (ja) * | 1993-10-14 | 1995-05-02 | Asahi Chem Ind Co Ltd | スタウロスポリン糖部分変換誘導体 |
| KR100340159B1 (ko) * | 1993-12-07 | 2002-11-23 | 일라이 릴리 앤드 캄파니 | 단백질키나제c억제제 |
| US5624949A (en) * | 1993-12-07 | 1997-04-29 | Eli Lilly And Company | Protein kinase C inhibitors |
| US5723456A (en) * | 1993-12-07 | 1998-03-03 | Eli Lilly & Company | Therapeutic treatment for cardiovascular diseases |
| EP1449529B1 (en) * | 1993-12-23 | 2010-01-27 | Eli Lilly And Company | Protein Kinase C Inhibitors |
| US5545636A (en) * | 1993-12-23 | 1996-08-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| WO1995032975A1 (en) * | 1994-06-01 | 1995-12-07 | Ciba-Geigy Ag | Indolocarbazole derivatives for sensitizing multidrug-resistant cells to antitumor agents |
| US5705511A (en) * | 1994-10-14 | 1998-01-06 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5475110A (en) * | 1994-10-14 | 1995-12-12 | Cephalon, Inc. | Fused Pyrrolocarbazoles |
| US5591855A (en) * | 1994-10-14 | 1997-01-07 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5594009A (en) * | 1994-10-14 | 1997-01-14 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| DE69629341T2 (de) * | 1995-03-09 | 2004-06-09 | Kyowa Hakko Kogyo Co., Ltd. | Pyrrolocarbazolderivate |
| WO1997007081A2 (en) * | 1995-08-11 | 1997-02-27 | Yale University | Glycosylated indolocarbazole synthesis |
| ES2122764T3 (es) * | 1995-11-20 | 1998-12-16 | Lilly Co Eli | Inhibidor de la proteina quinasa c. |
| CA2237401C (en) * | 1995-11-20 | 2003-10-21 | Eli Lilly And Company | Novel intermediates and their use to prepare n,n'-bridged bisindolylmaleimides |
| US5808060A (en) * | 1995-12-11 | 1998-09-15 | Cephalon, Inc. | Fused isoindolones |
| US5616724A (en) * | 1996-02-21 | 1997-04-01 | Cephalon, Inc. | Fused pyrrolo[2,3-c]carbazole-6-ones |
| BR9709301A (pt) * | 1996-05-01 | 1999-08-10 | Univ Mississipi | Inibidores da proteína quinase c halo-substituídos |
| AU721942B2 (en) * | 1996-06-25 | 2000-07-20 | Cephalon, Inc. | Use of K-252A derivative for the treatment of peripheral or central nerve disorders, and cytokine overproduction |
| BR9711306A (pt) * | 1996-08-22 | 1999-08-17 | Bristol Myers Squibb Co | Amino a-Úcar citotÄxico e derivados de a-Úcar correlatos de indolopirrolocarbazÄis |
| US5721272A (en) * | 1996-11-18 | 1998-02-24 | Eli Lilly And Company | Intermediates and their use to prepare N,N'-bridged bisindolylmaleimides |
| US6127401A (en) * | 1998-06-05 | 2000-10-03 | Cephalon, Inc. | Bridged indenopyrrolocarbazoles |
-
1999
- 1999-06-03 US US09/325,140 patent/US6127401A/en not_active Expired - Lifetime
- 1999-06-04 WO PCT/US1999/012531 patent/WO1999062523A1/en not_active Ceased
- 1999-06-04 ES ES99927234T patent/ES2228056T3/es not_active Expired - Lifetime
- 1999-06-04 DK DK99927234T patent/DK1083903T3/da active
- 1999-06-04 TR TR2000/03623T patent/TR200003623T2/xx unknown
- 1999-06-04 AT AT99927234T patent/ATE274348T1/de active
- 1999-06-04 PL PL344475A patent/PL198434B1/pl not_active IP Right Cessation
- 1999-06-04 CA CA002334189A patent/CA2334189C/en not_active Expired - Fee Related
- 1999-06-04 JP JP2000551779A patent/JP4481493B2/ja not_active Expired - Fee Related
- 1999-06-04 EA EA200100012A patent/EA004066B1/ru not_active IP Right Cessation
- 1999-06-04 CN CN99807036A patent/CN1304311A/zh active Pending
- 1999-06-04 SK SK1799-2000A patent/SK285368B6/sk not_active IP Right Cessation
- 1999-06-04 DE DE69919700T patent/DE69919700T2/de not_active Expired - Lifetime
- 1999-06-04 UA UA2001010125A patent/UA66865C2/uk unknown
- 1999-06-04 EP EP99927234A patent/EP1083903B1/en not_active Expired - Lifetime
- 1999-06-04 KR KR1020007013686A patent/KR100647753B1/ko not_active Expired - Fee Related
- 1999-06-04 NZ NZ508306A patent/NZ508306A/en unknown
- 1999-06-04 CZ CZ20004522A patent/CZ301754B6/cs not_active IP Right Cessation
- 1999-06-04 HU HU0102512A patent/HUP0102512A3/hu unknown
- 1999-06-04 PT PT99927234T patent/PT1083903E/pt unknown
- 1999-06-04 BR BR9910908-5A patent/BR9910908A/pt not_active Application Discontinuation
- 1999-06-04 AU AU44188/99A patent/AU744900B2/en not_active Ceased
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2000
- 2000-05-17 US US09/572,160 patent/US6359130B1/en not_active Expired - Fee Related
- 2000-12-04 NO NO20006166A patent/NO20006166L/no not_active Application Discontinuation
- 2000-12-07 BG BG105028A patent/BG65447B1/bg unknown
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