JP4405667B2 - Ｋ−２５２ａの３’−エピマー誘導体 - Google Patents
Ｋ−２５２ａの３’−エピマー誘導体 Download PDFInfo
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- JP4405667B2 JP4405667B2 JP2000526515A JP2000526515A JP4405667B2 JP 4405667 B2 JP4405667 B2 JP 4405667B2 JP 2000526515 A JP2000526515 A JP 2000526515A JP 2000526515 A JP2000526515 A JP 2000526515A JP 4405667 B2 JP4405667 B2 JP 4405667B2
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- Prior art keywords
- hydrogen
- unsubstituted
- lower alkyl
- substituted
- aryl
- Prior art date
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- KOZFSFOOLUUIGY-SOLYNIJKSA-N K-252a Chemical class C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@](C(=O)OC)(O)[C@]4(C)O1 KOZFSFOOLUUIGY-SOLYNIJKSA-N 0.000 title description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 61
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- 230000004083 survival effect Effects 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 239000001257 hydrogen Substances 0.000 claims description 58
- 150000002431 hydrogen Chemical group 0.000 claims description 37
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003107 substituted aryl group Chemical group 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- -1 CO 2 R 9 Chemical group 0.000 claims description 15
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 102000003923 Protein Kinase C Human genes 0.000 claims description 10
- 108090000315 Protein Kinase C Proteins 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 101100222854 Bacillus subtilis (strain 168) czcO gene Proteins 0.000 claims description 7
- 101100537961 Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88) trkA2 gene Proteins 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 101150025395 trkA gene Proteins 0.000 claims description 7
- 101150113435 trkA1 gene Proteins 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 3
- 230000026731 phosphorylation Effects 0.000 claims description 3
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 1
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 32
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- 238000000034 method Methods 0.000 description 28
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
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- 238000006243 chemical reaction Methods 0.000 description 15
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- VVVPGLRKXQSQSZ-UHFFFAOYSA-N indolo[3,2-c]carbazole Chemical compound C1=CC=CC2=NC3=C4C5=CC=CC=C5N=C4C=CC3=C21 VVVPGLRKXQSQSZ-UHFFFAOYSA-N 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
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- 239000003153 chemical reaction reagent Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
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- 108091000080 Phosphotransferase Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
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- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
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- 241000700159 Rattus Species 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
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- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 0 C=C(C1)[C@](C2)(O)OC1[n](c1c3cccc1)*1c3c(C(NC3)=O)c3c-3c1C2c1c-3cccc1 Chemical compound C=C(C1)[C@](C2)(O)OC1[n](c1c3cccc1)*1c3c(C(NC3)=O)c3c-3c1C2c1c-3cccc1 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
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- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 4
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- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 4
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- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
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- FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 3
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- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7026397P | 1997-12-31 | 1997-12-31 | |
| US60/070,263 | 1997-12-31 | ||
| PCT/US1998/027644 WO1999033836A1 (en) | 1997-12-31 | 1998-12-30 | 3'-epimeric k-252a derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2001527079A JP2001527079A (ja) | 2001-12-25 |
| JP2001527079A5 JP2001527079A5 (enExample) | 2005-12-22 |
| JP4405667B2 true JP4405667B2 (ja) | 2010-01-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000526515A Expired - Fee Related JP4405667B2 (ja) | 1997-12-31 | 1998-12-30 | Ｋ−２５２ａの３’−エピマー誘導体 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US6093713A (enExample) |
| EP (1) | EP1044203B1 (enExample) |
| JP (1) | JP4405667B2 (enExample) |
| KR (1) | KR20010033737A (enExample) |
| CN (1) | CN1285836A (enExample) |
| AT (1) | ATE234308T1 (enExample) |
| AU (1) | AU1947499A (enExample) |
| BR (1) | BR9814543A (enExample) |
| CA (1) | CA2315953C (enExample) |
| DE (1) | DE69812177T2 (enExample) |
| DK (1) | DK1044203T3 (enExample) |
| ES (1) | ES2194385T3 (enExample) |
| NO (1) | NO20003397L (enExample) |
| PT (1) | PT1044203E (enExample) |
| WO (1) | WO1999033836A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002227371B2 (en) * | 2000-12-08 | 2007-05-10 | Ortho-Mcneil Pharmaceutical, Inc. | Macroheterocylic compounds useful as kinase inhibitors |
| EP1721609A3 (en) * | 2001-05-16 | 2007-01-31 | GPC Biotech AG | Pyridylpyrimidine derivatives as effective compounds against prion diseases |
| US7018999B2 (en) | 2001-05-16 | 2006-03-28 | Cephalon, Inc. | Methods for the treatment and prevention of pain |
| DE10161940A1 (de) | 2001-12-17 | 2003-07-03 | Nad Ag | N-Carbacyclus-monosubstitutierte Indolocarbazole als Proteinkinase-inhibitoren |
| US6723844B1 (en) * | 2003-02-27 | 2004-04-20 | Abbott Laboratories | Preparation of K-252a |
| DE102004025726B4 (de) * | 2004-05-26 | 2006-07-06 | Roder, Hanno, Dr. | Verwendung eines spezifischen K252a-Derivats zur Verhinderung oder Behandlung der Alzheimerschen Krankheit |
| 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 |
| JP2010513287A (ja) * | 2006-12-14 | 2010-04-30 | トータティス， インク． | 癌治療のための組成物及び方法 |
Family Cites Families (10)
| 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 |
| 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 |
| DE3752123T2 (de) * | 1987-03-09 | 1998-05-14 | Kyowa Hakko Kogyo Kk | Derivate des physiologisch aktiven mittels k-252 |
| 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 |
| DK0699204T3 (da) | 1993-05-28 | 1999-02-22 | Cephalon Inc | Anvendelse af indolocarbazolderivater til behandling af en patologisk tilstand i prostata |
| US5468872A (en) * | 1993-09-16 | 1995-11-21 | Cephalon, Inc. | K-252a functional derivatives potentiate neurotrophin-3 for the treatment of neurological disorders |
| DE69520554T2 (de) * | 1994-07-04 | 2001-08-23 | Kyowa Hakko Kogyo Co., Ltd. | Verfahren zur herstellung von indolocarbazol-derivaten |
| WO1997005140A1 (en) | 1995-07-31 | 1997-02-13 | Novartis Ag | Trindene compounds |
| WO1997007081A2 (en) | 1995-08-11 | 1997-02-27 | Yale University | Glycosylated indolocarbazole synthesis |
-
1998
- 1998-12-30 WO PCT/US1998/027644 patent/WO1999033836A1/en not_active Ceased
- 1998-12-30 AT AT98964309T patent/ATE234308T1/de not_active IP Right Cessation
- 1998-12-30 CA CA2315953A patent/CA2315953C/en not_active Expired - Fee Related
- 1998-12-30 AU AU19474/99A patent/AU1947499A/en not_active Abandoned
- 1998-12-30 DE DE69812177T patent/DE69812177T2/de not_active Expired - Lifetime
- 1998-12-30 BR BR9814543-6A patent/BR9814543A/pt not_active Application Discontinuation
- 1998-12-30 CN CN98812812A patent/CN1285836A/zh active Pending
- 1998-12-30 US US09/223,518 patent/US6093713A/en not_active Expired - Lifetime
- 1998-12-30 KR KR1020007007260A patent/KR20010033737A/ko not_active Withdrawn
- 1998-12-30 ES ES98964309T patent/ES2194385T3/es not_active Expired - Lifetime
- 1998-12-30 PT PT98964309T patent/PT1044203E/pt unknown
- 1998-12-30 JP JP2000526515A patent/JP4405667B2/ja not_active Expired - Fee Related
- 1998-12-30 DK DK98964309T patent/DK1044203T3/da active
- 1998-12-30 EP EP98964309A patent/EP1044203B1/en not_active Expired - Lifetime
-
2000
- 2000-02-15 US US09/503,812 patent/US6451786B1/en not_active Expired - Fee Related
- 2000-06-29 NO NO20003397A patent/NO20003397L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2315953A1 (en) | 1999-07-08 |
| WO1999033836A1 (en) | 1999-07-08 |
| EP1044203B1 (en) | 2003-03-12 |
| KR20010033737A (ko) | 2001-04-25 |
| ATE234308T1 (de) | 2003-03-15 |
| DE69812177D1 (de) | 2003-04-17 |
| AU1947499A (en) | 1999-07-19 |
| NO20003397L (no) | 2000-08-31 |
| US6451786B1 (en) | 2002-09-17 |
| DK1044203T3 (da) | 2003-07-14 |
| ES2194385T3 (es) | 2003-11-16 |
| BR9814543A (pt) | 2000-10-10 |
| EP1044203A1 (en) | 2000-10-18 |
| WO1999033836A9 (en) | 2000-09-14 |
| CN1285836A (zh) | 2001-02-28 |
| CA2315953C (en) | 2010-11-09 |
| JP2001527079A (ja) | 2001-12-25 |
| PT1044203E (pt) | 2003-07-31 |
| DE69812177T2 (de) | 2004-01-15 |
| NO20003397D0 (no) | 2000-06-29 |
| US6093713A (en) | 2000-07-25 |
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