FI114864B - Förfarande för framställning av terapeutisk användbara indolokarbazolderivat - Google Patents
Förfarande för framställning av terapeutisk användbara indolokarbazolderivat Download PDFInfo
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- FI114864B FI114864B FI20031516A FI20031516A FI114864B FI 114864 B FI114864 B FI 114864B FI 20031516 A FI20031516 A FI 20031516A FI 20031516 A FI20031516 A FI 20031516A FI 114864 B FI114864 B FI 114864B
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
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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
- A61K31/33—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Epidemiology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (13)
1. Förfarande för framställning av ett terapeu-tiskt användbart indolkarbazolderivat med formeln (VI) 5 H (Ηγ° h3c^ ] HO-"] COXK 23 (VI) väri R1 är -CH(SC6H5)2, -CH(-SCH2CH2S-) , -CH2SR24 eller -
10 CH=NR25; R24 är bensimidazol-2-yl, furfuryl, 2- dimetylaminoetyl eller 1H-1,2,4-triazol-3-yl; och R25 är pyrrolidin-1-yl, pyridin-2-ylamino, guanidi-no, N-morfolino, dimetylamino eller 4-metylpiperazin-l-yl; 15 eller för framställning av dess farmaceutiskt godtagbara sait, kännetecknat av att : a) för framställning av en förening enligt formel ·*; (VI), väri R1 är -CH(SC6H5)2 eller -CH (-SCH2CH2S-) , bringas en förening med formeln .···. 20 COCK I 3 Υγο ^γ^ντγ0Η0 U°x/ h3c^ i ‘ HzCCOf^\ C02CH3 (A) 114864 i kontakt med en motsvarande merkaptan i närvaro av en Le-wis-syra i ett inert lösningsmedel, varvid erhälls en fö-rening raed formeln COCH, I 3 cV° H3C^ j H3CCOf^\ co2ch3 (A-i) 5 och föreningen enligt formel (A-i) deacetyleras; b) för framställning av en förening enligt formel (VI), väri R1 är -CH2SR24 och R24 har definierats ovan, bringas ovan nämnda förening enligt formel (A) i kontakt 10 med en motsvarande merkaptan i närvaro av en syra i ett inert lösningsmedel, varvid erhälls en förening med nämnda formel (A-i), och föreningen enligt formel (A-i) deacetyleras; •t c) för framställning av en förening enligt formel 15 (VI) , väri R1 är -CH=NR25 och R25 har definierats ovan, I f bringas ovan nämnda förening enligt formel (A) i kontakt : med ett motsvarande hydrazin i närvaro av en syra i ett • · ' inert lösningsmedel, varvid erhälls en förening med nämnda t , ,* formel (A- i) , i>t>: 20 och föreningen med formeln (A-i) deacetyleras; och d) om sä önskas, omvandlas den sälunda erhällna ·· föreningen enligt formel (VI) tili sitt farmaceutiskt god- tagbara sait. >;> 2. Förfarande enligt patentkrav 1, känneteck- 25 nat av att en förening enligt formel (VI) framställs, väri R1 är -CH(SC6H5)2.
3. Förfarande enligt patentkrav 1, känneteck-: n a t av att en förening enligt formel (VI) framställs, väri R1 är -CH (-SCH2CH2S-) . 114864
4. Förfarande enligt patentkrav 1, känneteck- nat av att en förening enligt formel (VI) framställs, väri R1 är -CH2SR24 och R24 är bensimidazol-2-yl.
5. Förfarande enligt patentkrav 1, känneteck-5 nat av att en förening enligt formel (VI) framställs, väri R1 är -CH2SR24 och R24 är furfuryl.
6. Förfarande enligt patentkrav 1, känneteck- nat av att en förening enligt formel (VI) framställs, väri R1 är -CH2SR24 och R24 är -CH2CH2N (CH3) 2. 10 7. Förfarande enligt patentkrav 1, känneteck- nat av att en förening enligt formel (VI) framställs, väri R1 är -CH2SR24 och R24 är 1H-1,2,4 - triazol-3-yl.
8. Förfarande enligt patentkrav 1, känneteck- nat av att en förening enligt formel (VI) framställs, 15 väri R1 är -CH=NR25 och R25 är pyrrolidin-l-yl.
9. Förfarande enligt patentkrav 1, känneteck- nat av att en förening enligt formel (VI) framställs, väri R1 är -CH=NR25 och R25 är pyridin-2-yl-amino.
10. Förfarande enligt patentkrav 1, känneteck- 20 nat av att en förening enligt formel (VI) framställs, väri R1 är -CH=NNHC (=N) NH2 .
11. Förfarande enligt patentkrav 1, känneteck- ; n at av att en förening enligt formel (VI) framställs, väri R1 är -CH=N-N (CH3) 2 . j 25 12. Förfarande enligt patentkrav 1, känneteck- nat av att en förening enligt formel (VI) framställs, väri R1 är -CH=NR25 och R25 är morfolino.
13. Förfarande enligt patentkrav 1, känneteck-nat av att en förening enligt formel (VI) framställs, 30 väri R1 är -CH=NR25 och R25 är 4-metyl-piperazin-l-yl. * » * 1 t » · 1 i > i 1 »
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6917893A | 1993-05-28 | 1993-05-28 | |
| US6917893 | 1993-05-28 | ||
| US9662293A | 1993-07-22 | 1993-07-22 | |
| US9662293 | 1993-07-22 | ||
| US9406082 | 1994-05-27 | ||
| PCT/US1994/006082 WO1994027982A1 (en) | 1993-05-28 | 1994-05-27 | Use of indolocarbazole derivatives to treat a pathological condition of the prostate |
Publications (2)
| Publication Number | Publication Date |
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| FI20031516A FI20031516A (sv) | 2003-10-16 |
| FI114864B true FI114864B (sv) | 2005-01-14 |
Family
ID=26749764
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| Application Number | Title | Priority Date | Filing Date |
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| FI955709A FI113537B (sv) | 1993-05-28 | 1995-11-27 | Förfarande för framställning av terapeutiskt användbara indolokarbazolderivat |
| FI20031516A FI114864B (sv) | 1993-05-28 | 2003-10-16 | Förfarande för framställning av terapeutisk användbara indolokarbazolderivat |
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| Application Number | Title | Priority Date | Filing Date |
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| FI955709A FI113537B (sv) | 1993-05-28 | 1995-11-27 | Förfarande för framställning av terapeutiskt användbara indolokarbazolderivat |
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| US (2) | US5516771A (sv) |
| EP (2) | EP0839814A3 (sv) |
| JP (2) | JP3344586B2 (sv) |
| KR (1) | KR100201343B1 (sv) |
| AT (1) | ATE165097T1 (sv) |
| AU (1) | AU679752B2 (sv) |
| CA (1) | CA2163904C (sv) |
| DE (1) | DE69409641T2 (sv) |
| DK (1) | DK0699204T3 (sv) |
| ES (1) | ES2118414T3 (sv) |
| FI (2) | FI113537B (sv) |
| NO (1) | NO306902B1 (sv) |
| NZ (1) | NZ267337A (sv) |
| WO (1) | WO1994027982A1 (sv) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5756494A (en) * | 1992-07-24 | 1998-05-26 | Cephalon, Inc. | Protein kinase inhibitors for treatment of neurological disorders |
| DE4243321A1 (de) * | 1992-12-21 | 1994-06-23 | Goedecke Ag | Aminosäurederivate von Heterocyclen als PKC-Inhibitoren |
| DE69505470T2 (de) * | 1994-08-04 | 1999-05-12 | F. Hoffmann-La Roche Ag, Basel | Pyrrolocarbazol |
| US5650407A (en) * | 1995-04-05 | 1997-07-22 | Cephalon, Inc. | Selected soluble esters of hydroxyl-containing indolocarbazoles |
| US5686444A (en) | 1995-04-05 | 1997-11-11 | Cephalon, Inc. | Selected soluble esters of hydroxyl-containing indolocarbazoles |
| US6676935B2 (en) | 1995-06-27 | 2004-01-13 | Cell Genesys, Inc. | Tissue specific adenoviral vectors |
| US6197293B1 (en) * | 1997-03-03 | 2001-03-06 | Calydon, Inc. | Adenovirus vectors specific for cells expressing androgen receptor and methods of use thereof |
| US5808060A (en) * | 1995-12-11 | 1998-09-15 | Cephalon, Inc. | Fused isoindolones |
| WO1997040830A1 (en) | 1996-05-01 | 1997-11-06 | Eli Lilly And Company | Therapeutic treatment for vegf related diseases |
| US6875865B1 (en) | 1996-06-03 | 2005-04-05 | Cephalon, Inc. | Selected derivatives of K-252a |
| UA67725C2 (en) | 1996-06-03 | 2004-07-15 | Cephalon Inc | K-252a derivatives and a method for improvement of functioning and cell survival enhancement |
| EP0912184B1 (en) | 1996-06-25 | 2002-09-25 | Cephalon, Inc. | Use of k-252a derivative for the treatment of peripheral or central nerve disorders, and cytokine overproduction |
| HUP0003194A3 (en) * | 1997-08-15 | 2003-03-28 | Cephalon Inc West Chester | Use of tyrosine kinase inhibitor in synergic pharmaceutical composition treating prostate cancer |
| DE69812177T2 (de) | 1997-12-31 | 2004-01-15 | Cephalon Inc | 3'-epi k-252a derivate |
| US6127401A (en) * | 1998-06-05 | 2000-10-03 | Cephalon, Inc. | Bridged indenopyrrolocarbazoles |
| US6013646A (en) * | 1998-07-02 | 2000-01-11 | Bayer Corporation | Indolocarbazole derivatives useful for the treatment of neurodegenerative diseases and cancer |
| US6200968B1 (en) | 1998-08-06 | 2001-03-13 | Cephalon, Inc. | Particle-forming compositions containing fused pyrrolocarbazoles |
| US7795246B2 (en) * | 1998-08-06 | 2010-09-14 | Cephalon, Inc. | Particle-forming compositions containing fused pyrrolocarbazoles |
| NZ511024A (en) | 1998-09-25 | 2003-10-31 | Cephalon Inc | Methods for preventing/treating damage to sensory hair cells, loss of hearing and cochlear neurons using fused pyrrolocarbazoles |
| ATE406907T1 (de) * | 1998-10-28 | 2008-09-15 | Cornell Res Foundation Inc | Methoden zur regulierung der angiogenese und vaskuläre integrität mittels trk rezeptor liganden bdnf, nt-3 und nt-4 |
| US6841567B1 (en) | 1999-02-12 | 2005-01-11 | Cephalon, Inc. | Cyclic substituted fused pyrrolocarbazoles and isoindolones |
| US6472385B1 (en) * | 1999-08-09 | 2002-10-29 | Trustees Of Darmouth College | Compositions and methods to enhance cancer chemotherapy in p53 defective tumors |
| US6399780B1 (en) * | 1999-08-20 | 2002-06-04 | Cephalon, Inc. | Isomeric fused pyrrolocarbazoles and isoindolones |
| US7129250B2 (en) | 2000-05-19 | 2006-10-31 | Aegera Therapeutics Inc. | Neuroprotective and anti-proliferative compounds |
| US7018999B2 (en) * | 2001-05-16 | 2006-03-28 | Cephalon, Inc. | Methods for the treatment and prevention of pain |
| IL144583A0 (en) * | 2001-07-26 | 2002-05-23 | Peptor Ltd | Chimeric protein kinase inhibitors |
| IL156429A0 (en) * | 2003-06-12 | 2004-01-04 | Peptor Ltd | Cell permeable conjugates of peptides for inhibition of protein kinases |
| CA2625291A1 (en) | 2005-10-11 | 2007-04-19 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Egfr dependent modulation of chemokine expression and influence on therapy and diagnosis of tumors and side effects thereof |
| US20080021013A1 (en) * | 2006-07-21 | 2008-01-24 | Cephalon, Inc. | JAK inhibitors for treatment of myeloproliferative disorders |
| US20090155352A1 (en) * | 2007-11-20 | 2009-06-18 | Cephalon, Inc. | Microemulsion containing indolocarbazole compound and dosage forms containing the same |
| EA037709B1 (ru) | 2012-12-21 | 2021-05-13 | Сюкехюсе Сёрланне Хф | Способ лечения невропатической боли |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62155284A (ja) * | 1985-12-27 | 1987-07-10 | Kyowa Hakko Kogyo Co Ltd | 生理活性物質ｋ−２５２の誘導体 |
| JPS62155285A (ja) * | 1985-12-27 | 1987-07-10 | Kyowa Hakko Kogyo Co Ltd | 生理活性物質ｋ−２５２の誘導体 |
| JPS62240689A (ja) * | 1986-04-07 | 1987-10-21 | Meiji Seika Kaisha Ltd | Ｓｆ−２３７０物質誘導体及びその製法 |
| JPH0826037B2 (ja) * | 1987-01-22 | 1996-03-13 | 協和醗酵工業株式会社 | 生理活性物質ｋ−２５２の誘導体 |
| JPH0826036B2 (ja) * | 1987-01-22 | 1996-03-13 | 協和醗酵工業株式会社 | 生理活性物質ｋ−２５２の誘導体 |
| EP0303697B1 (en) * | 1987-03-09 | 1997-10-01 | Kyowa Hakko Kogyo Co., Ltd. | Derivatives of physiologically active substance 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 |
| DE3803620A1 (de) * | 1988-02-06 | 1989-08-17 | Goedecke Ag | Indolocarbazol-derivate, verfahren zu deren herstellung und diese enthaltende arzneimittel |
| US5073633A (en) * | 1989-03-23 | 1991-12-17 | Bristol-Myers Company | BMY-41950 antitumor antibiotic |
| DE3924538A1 (de) * | 1989-07-25 | 1991-01-31 | Goedecke Ag | Indolocarbazol und dessen verwendung |
| CA2112799A1 (en) * | 1991-07-03 | 1993-01-21 | Stephen P. Squinto | Method and assay system for neurotrophin activity |
| WO1993008809A1 (en) * | 1991-11-08 | 1993-05-13 | The University Of Southern California | Compositions containing k-252 compounds for potentiation of neurotrophin activity |
| US6271242B1 (en) * | 1992-02-10 | 2001-08-07 | Bristol-Myers Squibb Co. | Method for treating cancer using a tyrosine protein kinase inhibitor |
| US5461146A (en) * | 1992-07-24 | 1995-10-24 | Cephalon, Inc. | Selected protein kinase inhibitors for the treatment of neurological disorders |
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1994
- 1994-05-27 DK DK94918168T patent/DK0699204T3/da active
- 1994-05-27 CA CA002163904A patent/CA2163904C/en not_active Expired - Fee Related
- 1994-05-27 NZ NZ267337A patent/NZ267337A/en not_active IP Right Cessation
- 1994-05-27 EP EP98200023A patent/EP0839814A3/en not_active Withdrawn
- 1994-05-27 DE DE69409641T patent/DE69409641T2/de not_active Expired - Lifetime
- 1994-05-27 ES ES94918168T patent/ES2118414T3/es not_active Expired - Lifetime
- 1994-05-27 WO PCT/US1994/006082 patent/WO1994027982A1/en active IP Right Grant
- 1994-05-27 AU AU69607/94A patent/AU679752B2/en not_active Ceased
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- 1994-05-27 AT AT94918168T patent/ATE165097T1/de not_active IP Right Cessation
- 1994-05-27 EP EP94918168A patent/EP0699204B1/en not_active Expired - Lifetime
- 1994-05-27 JP JP50102695A patent/JP3344586B2/ja not_active Expired - Fee Related
- 1994-05-27 KR KR1019950705338A patent/KR100201343B1/ko not_active IP Right Cessation
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- 1995-11-27 NO NO954816A patent/NO306902B1/no not_active IP Right Cessation
- 1995-11-27 FI FI955709A patent/FI113537B/sv not_active IP Right Cessation
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Also Published As
| Publication number | Publication date |
|---|---|
| AU6960794A (en) | 1994-12-20 |
| EP0699204A4 (en) | 1996-01-10 |
| CA2163904C (en) | 2000-01-25 |
| EP0699204B1 (en) | 1998-04-15 |
| JP2002504064A (ja) | 2002-02-05 |
| CA2163904A1 (en) | 1994-12-08 |
| US5516771A (en) | 1996-05-14 |
| FI20031516A (sv) | 2003-10-16 |
| JP2002356487A (ja) | 2002-12-13 |
| NO954816D0 (no) | 1995-11-27 |
| DE69409641D1 (de) | 1998-05-20 |
| AU679752B2 (en) | 1997-07-10 |
| EP0839814A2 (en) | 1998-05-06 |
| DE69409641T2 (de) | 1998-11-26 |
| KR100201343B1 (ko) | 1999-06-15 |
| EP0839814A3 (en) | 1998-09-16 |
| NZ267337A (en) | 2005-01-28 |
| FI113537B (sv) | 2004-05-14 |
| JP3727613B2 (ja) | 2005-12-14 |
| NO306902B1 (no) | 2000-01-10 |
| FI955709A (sv) | 1996-01-03 |
| FI955709A0 (sv) | 1995-11-27 |
| DK0699204T3 (da) | 1999-02-22 |
| ES2118414T3 (es) | 1998-09-16 |
| NO954816L (no) | 1996-01-26 |
| KR960702838A (ko) | 1996-05-23 |
| EP0699204A1 (en) | 1996-03-06 |
| US5654427A (en) | 1997-08-05 |
| JP3344586B2 (ja) | 2002-11-11 |
| WO1994027982A1 (en) | 1994-12-08 |
| ATE165097T1 (de) | 1998-05-15 |
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