DE60101000T2 - N-heterocyclische derivate als nos inhibitoren - Google Patents
N-heterocyclische derivate als nos inhibitoren Download PDFInfo
- Publication number
- DE60101000T2 DE60101000T2 DE60101000T DE60101000T DE60101000T2 DE 60101000 T2 DE60101000 T2 DE 60101000T2 DE 60101000 T DE60101000 T DE 60101000T DE 60101000 T DE60101000 T DE 60101000T DE 60101000 T2 DE60101000 T2 DE 60101000T2
- Authority
- DE
- Germany
- Prior art keywords
- hydrogen
- alkyl
- benzodioxol
- methyl
- imidazol
- 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 - Lifetime
Links
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- 150000001875 compounds Chemical class 0.000 claims abstract description 243
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 169
- 239000001257 hydrogen Substances 0.000 claims description 169
- 125000000217 alkyl group Chemical group 0.000 claims description 135
- -1 1-piperazinyl Chemical group 0.000 claims description 120
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 89
- 150000002431 hydrogen Chemical class 0.000 claims description 80
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 72
- 229910052736 halogen Inorganic materials 0.000 claims description 52
- 150000002367 halogens Chemical class 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 239000000460 chlorine Substances 0.000 claims description 26
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 26
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 24
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 24
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- 239000011737 fluorine Substances 0.000 claims description 23
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 22
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
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- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 16
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 16
- 230000005856 abnormality Effects 0.000 claims description 12
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- HMJJJFURDXCCMU-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yloxy)-6-(4-imidazol-1-yl-2-methylphenoxy)pyridine Chemical compound C=1C=C(OC=2N=C(OC=3C=C4OCOC4=CC=3)C=CC=2)C(C)=CC=1N1C=CN=C1 HMJJJFURDXCCMU-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
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Landscapes
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- Engineering & Computer Science (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US19216800P | 2000-03-27 | 2000-03-27 | |
| US192168P | 2000-03-27 | ||
| US09/814,787 US6525051B2 (en) | 2000-03-27 | 2001-03-22 | N-heterocyclic derivatives as NOS inhibitors |
| US814787 | 2001-03-22 | ||
| PCT/US2001/009481 WO2001072744A1 (en) | 2000-03-27 | 2001-03-26 | N-heterocyclic derivatives as nos inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60101000D1 DE60101000D1 (de) | 2003-11-20 |
| DE60101000T2 true DE60101000T2 (de) | 2004-07-29 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60101000T Expired - Lifetime DE60101000T2 (de) | 2000-03-27 | 2001-03-26 | N-heterocyclische derivate als nos inhibitoren |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6525051B2 (enExample) |
| EP (1) | EP1268471B1 (enExample) |
| JP (1) | JP2003528871A (enExample) |
| AT (1) | ATE252097T1 (enExample) |
| AU (1) | AU2001245972A1 (enExample) |
| DE (1) | DE60101000T2 (enExample) |
| DK (1) | DK1268471T3 (enExample) |
| ES (1) | ES2208578T3 (enExample) |
| HK (1) | HK1053834A1 (enExample) |
| NO (1) | NO20024614L (enExample) |
| PT (1) | PT1268471E (enExample) |
| TR (1) | TR200302268T4 (enExample) |
| WO (1) | WO2001072744A1 (enExample) |
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| US6432947B1 (en) | 1997-02-19 | 2002-08-13 | Berlex Laboratories, Inc. | N-heterocyclic derivatives as NOS inhibitors |
| US7012098B2 (en) * | 2001-03-23 | 2006-03-14 | Pharmacia Corporation | Inhibitors of inducible nitric oxide synthase for chemoprevention and treatment of cancers |
| CN100349876C (zh) * | 2001-11-30 | 2007-11-21 | 辛塔医药品有限公司 | 嘧啶化合物 |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| EP1795192A3 (en) * | 2002-04-30 | 2008-05-07 | Bayer Schering Pharma Aktiengesellschaft | 1-(Pyridazin-3-yl)-imidazole derivatives as inhibitors of nitric oxide synthase (NOS) |
| US6982259B2 (en) * | 2002-04-30 | 2006-01-03 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
| IL166241A0 (en) * | 2002-07-29 | 2006-01-15 | Rigel Pharmaceuticals Inc | Method of treating or preventing autoimmune diseases with 2,4-pyrimidinedinediamine compounds |
| US7109337B2 (en) | 2002-12-20 | 2006-09-19 | Pfizer Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| ATE458731T1 (de) | 2002-12-20 | 2010-03-15 | Pfizer Prod Inc | Pyrimidin-derivate zur behandlung von anormalem zellwachstum |
| US20080058297A1 (en) * | 2003-05-29 | 2008-03-06 | Synta Pharmaceuticals Corp. | Heterocyclic Compounds For Preventing And Treating Disorders Associated With Excessive Bone Loss |
| RS53109B (sr) | 2003-07-30 | 2014-06-30 | Rigel Pharmaceuticals Inc. | Jedinjenja 2,4 pirimidindiamina za upotrebu u tretmanu ili prevenciji autoimunih bolesti |
| JP2007537235A (ja) | 2004-05-14 | 2007-12-20 | ファイザー・プロダクツ・インク | 異常細胞増殖の治療用ピリミジン誘導体 |
| EP1758887A1 (en) | 2004-05-14 | 2007-03-07 | Pfizer Products Incorporated | Pyrimidine derivatives for the treatment of abnormal cell growth |
| CA2566332A1 (en) | 2004-05-14 | 2005-11-24 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
| TW200612948A (en) * | 2004-07-01 | 2006-05-01 | Synta Pharmaceuticals Corp | 2-substituted heteroaryl compounds |
| ES2380550T3 (es) * | 2004-11-24 | 2012-05-16 | Rigel Pharmaceuticals, Inc. | Compuestos de espiro-2,4-pirimidindiamina y sus usos |
| US7622583B2 (en) | 2005-01-14 | 2009-11-24 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2 |
| AU2006204750C1 (en) * | 2005-01-14 | 2012-11-01 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2 |
| NZ555947A (en) | 2005-01-19 | 2010-11-26 | Rigel Pharmaceuticals Inc | Prodrugs of 2,4-pyrimidinediamine compounds and their uses |
| CA2604551A1 (en) * | 2005-05-03 | 2007-03-08 | Rigel Pharmaceuticals, Inc. | Jak kinase inhibitors and their uses |
| WO2007039578A1 (en) * | 2005-10-05 | 2007-04-12 | Nycomed Gmbh | Imidazolyl-substituted azabenzophenone compounds |
| JP4782239B2 (ja) | 2007-04-18 | 2011-09-28 | ファイザー・プロダクツ・インク | 異常細胞増殖治療のためのスルホニルアミド誘導体 |
| KR101617050B1 (ko) | 2007-07-12 | 2016-05-02 | 케모센트릭스, 인크. | 염증의 치료를 위한 ｃｃｒ2 조절물질로서 융합된 헤테로아릴 피리딜과 페닐 벤젠술폰아마이드 |
| US8063058B2 (en) * | 2008-04-16 | 2011-11-22 | Portola Pharmaceuticals, Inc. | Inhibitors of syk and JAK protein kinases |
| US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| AU2009248923B2 (en) | 2008-05-21 | 2015-01-29 | Takeda Pharmaceutical Company Limited | Phosphorous derivatives as kinase inhibitors |
| US9834518B2 (en) | 2011-05-04 | 2017-12-05 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| CA2856301C (en) | 2011-11-23 | 2020-10-06 | Portola Pharmaceuticals, Inc. | Pyrazine kinase inhibitors |
| JP6469567B2 (ja) | 2012-05-05 | 2019-02-13 | アリアド・ファーマシューティカルズ・インコーポレイテッド | Ｅｇｆｒ発動性がんの細胞増殖阻害用化合物 |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN110177549A (zh) | 2016-11-23 | 2019-08-27 | 坎莫森特里克斯公司 | 治疗局灶性节段性肾小球硬化的方法 |
| US11098026B2 (en) * | 2017-03-13 | 2021-08-24 | Impetis Biosciences Limited | Fused bicyclic compounds, compositions and applications thereof |
| SG11202002975YA (en) | 2017-10-11 | 2020-04-29 | Chemocentryx Inc | Treatment of focal segmental glomerulosclerosis with ccr2 antagonists |
| KR102563834B1 (ko) * | 2021-06-28 | 2023-08-04 | 순천대학교 산학협력단 | 세포자멸사를 유도하는 신규한 화합물 및 이를 포함하는 항암용 조성물 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6339875A (ja) | 1986-08-05 | 1988-02-20 | Nissin Food Prod Co Ltd | ピリミジン誘導体 |
| DE4118720A1 (de) | 1991-06-07 | 1992-12-10 | Bayer Ag | Substituierte imidazolinylpyrimidine |
| WO1993017009A1 (fr) | 1992-02-28 | 1993-09-02 | Zenyaku Kogyo Kabushiki Kaisha | DERIVE DE s-TRIAZINE ET REMEDE CONTRE DES MALADIES DEPENDENTES DE L'×STROGENE LE CONTENANT COMME INGREDIENT ACTIF |
| US5593992A (en) | 1993-07-16 | 1997-01-14 | Smithkline Beecham Corporation | Compounds |
| ES2114662T3 (es) | 1993-08-26 | 1998-06-01 | Ono Pharmaceutical Co | Derivados de la 4-aminopirimidina. |
| US5426110A (en) | 1993-10-06 | 1995-06-20 | Eli Lilly And Company | Pyrimidinyl-glutamic acid derivatives |
| US5629322A (en) | 1994-11-15 | 1997-05-13 | Merck & Co., Inc. | Cyclic amidine analogs as inhibitors of nitric oxide synthase |
| WO1996014842A1 (en) | 1994-11-15 | 1996-05-23 | Merck & Co., Inc. | Substituted heterocycles as inhibitors of nitric oxide synthase |
| DK0813525T3 (da) * | 1995-03-10 | 2004-02-16 | Berlex Lab | Benzamidinderivater, deres fremstilling og anvendelse som antikoagulanter |
| DE19541146A1 (de) * | 1995-10-25 | 1997-04-30 | Schering Ag | Imidazolderivate und deren Verwendung als Stickstoffmonoxid-Synthase-Inhibitoren |
| ZA977427B (en) | 1996-09-04 | 1998-03-02 | Dainippon Pharmaceutical Co | 2,4-disubstituted pyrimidine derivative, process for preparing the same, and a pharmaceutical composition containing the same. |
| WO1998027108A2 (en) * | 1996-12-16 | 1998-06-25 | Fujisawa Pharmaceutical Co., Ltd. | New amide compounds and their use as nitric oxide synthase inhibitors |
| PL335235A1 (en) | 1997-02-19 | 2000-04-10 | Berlex Lab | N-heterocyclic derivatives as nos inhibitors |
-
2001
- 2001-03-22 US US09/814,787 patent/US6525051B2/en not_active Expired - Fee Related
- 2001-03-26 DE DE60101000T patent/DE60101000T2/de not_active Expired - Lifetime
- 2001-03-26 PT PT01918958T patent/PT1268471E/pt unknown
- 2001-03-26 TR TR2003/02268T patent/TR200302268T4/xx unknown
- 2001-03-26 HK HK03104720.6A patent/HK1053834A1/zh unknown
- 2001-03-26 JP JP2001570654A patent/JP2003528871A/ja not_active Ceased
- 2001-03-26 AT AT01918958T patent/ATE252097T1/de not_active IP Right Cessation
- 2001-03-26 EP EP01918958A patent/EP1268471B1/en not_active Expired - Lifetime
- 2001-03-26 DK DK01918958T patent/DK1268471T3/da active
- 2001-03-26 AU AU2001245972A patent/AU2001245972A1/en not_active Abandoned
- 2001-03-26 ES ES01918958T patent/ES2208578T3/es not_active Expired - Lifetime
- 2001-03-26 WO PCT/US2001/009481 patent/WO2001072744A1/en not_active Ceased
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2002
- 2002-09-26 NO NO20024614A patent/NO20024614L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| PT1268471E (pt) | 2004-03-31 |
| DE60101000D1 (de) | 2003-11-20 |
| US6525051B2 (en) | 2003-02-25 |
| HK1053834A1 (zh) | 2003-11-07 |
| ATE252097T1 (de) | 2003-11-15 |
| NO20024614L (no) | 2002-11-26 |
| DK1268471T3 (da) | 2004-02-09 |
| TR200302268T4 (tr) | 2004-01-21 |
| JP2003528871A (ja) | 2003-09-30 |
| US20020010190A1 (en) | 2002-01-24 |
| AU2001245972A1 (en) | 2001-10-08 |
| EP1268471A1 (en) | 2003-01-02 |
| ES2208578T3 (es) | 2004-06-16 |
| EP1268471B1 (en) | 2003-10-15 |
| WO2001072744A1 (en) | 2001-10-04 |
| NO20024614D0 (no) | 2002-09-26 |
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