NO332550B1 - 2,4-Pyrimidindiamin-forbindelser for anvendelse ved behandling av en autoimmun sykdom forskjellig fra ulcerativ kolitt, Crohn's sykdom, inflammatorisk tarm og idiopatisk inflammatorisk tarmsykdom - Google Patents
2,4-Pyrimidindiamin-forbindelser for anvendelse ved behandling av en autoimmun sykdom forskjellig fra ulcerativ kolitt, Crohn's sykdom, inflammatorisk tarm og idiopatisk inflammatorisk tarmsykdom Download PDFInfo
- Publication number
- NO332550B1 NO332550B1 NO20051069A NO20051069A NO332550B1 NO 332550 B1 NO332550 B1 NO 332550B1 NO 20051069 A NO20051069 A NO 20051069A NO 20051069 A NO20051069 A NO 20051069A NO 332550 B1 NO332550 B1 NO 332550B1
- Authority
- NO
- Norway
- Prior art keywords
- fluoro
- pyrimidinediamine
- oxazin
- oxo
- benz
- Prior art date
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- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical class NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 title claims abstract description 119
- 208000023275 Autoimmune disease Diseases 0.000 title claims abstract description 48
- 208000022559 Inflammatory bowel disease Diseases 0.000 title claims description 16
- 206010009900 Colitis ulcerative Diseases 0.000 title claims description 10
- 201000006704 Ulcerative Colitis Diseases 0.000 title claims description 10
- 208000011231 Crohn disease Diseases 0.000 title claims description 8
- 230000002757 inflammatory effect Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 317
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 18
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- -1 2,4-pyrimidinediamine compound Chemical class 0.000 claims description 157
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 94
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 125000001072 heteroaryl group Chemical group 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 41
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- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 19
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 19
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- GMMWNTHAIOJBSD-UHFFFAOYSA-N 6-chloro-4-n-(2,3-dimethylphenyl)-2-n,2-n-dimethylpyrimidine-2,4-diamine Chemical compound CN(C)C1=NC(Cl)=CC(NC=2C(=C(C)C=CC=2)C)=N1 GMMWNTHAIOJBSD-UHFFFAOYSA-N 0.000 claims description 9
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
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- ZKJIIAKNIYSDCZ-UHFFFAOYSA-N 6-[[2-[[4-(aminomethylidene)cyclohexa-1,5-dien-1-yl]amino]-5-fluoropyrimidin-4-yl]amino]-2,2-difluoro-4h-1,4-benzoxazin-3-one Chemical compound C1=CC(=CN)CC=C1NC1=NC=C(F)C(NC=2C=C3NC(=O)C(F)(F)OC3=CC=2)=N1 ZKJIIAKNIYSDCZ-UHFFFAOYSA-N 0.000 claims description 3
- NTBPXIMLFVVNHZ-HZPDHXFCSA-N 7-[[2-[[(1r,2r)-2-aminocyclohexyl]amino]-5-fluoropyrimidin-4-yl]amino]-4,4-dimethylisoquinoline-1,3-dione Chemical compound C=1C=C2C(C)(C)C(=O)NC(=O)C2=CC=1NC(C(=CN=1)F)=NC=1N[C@@H]1CCCC[C@H]1N NTBPXIMLFVVNHZ-HZPDHXFCSA-N 0.000 claims description 3
- NXJKVKGXCFMYKD-UHFFFAOYSA-N 7-[[2-[[4-(aminomethylidene)cyclohexa-1,5-dien-1-yl]amino]-5-fluoropyrimidin-4-yl]amino]-4,4-dimethylisoquinoline-1,3-dione Chemical compound C=1C=C2C(C)(C)C(=O)NC(=O)C2=CC=1NC(C(=CN=1)F)=NC=1NC1=CCC(=CN)C=C1 NXJKVKGXCFMYKD-UHFFFAOYSA-N 0.000 claims description 3
- 208000004300 Atrophic Gastritis Diseases 0.000 claims description 3
- 206010050245 Autoimmune thrombocytopenia Diseases 0.000 claims description 3
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- DCPNWVPNKZLPOO-UHFFFAOYSA-N 2-n-[4-(aminomethylidene)cyclohexa-1,5-dien-1-yl]-4-n-(3,5-dimethoxyphenyl)-5-fluoropyrimidine-2,4-diamine Chemical compound COC1=CC(OC)=CC(NC=2C(=CN=C(NC=3C=CC(=CN)CC=3)N=2)F)=C1 DCPNWVPNKZLPOO-UHFFFAOYSA-N 0.000 claims description 2
- QQTSKXIDHUIHDT-UHFFFAOYSA-N 4-[[4-[(2,2-difluoro-3-oxo-4h-1,4-benzoxazin-6-yl)amino]-5-fluoropyrimidin-2-yl]amino]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1NC1=NC=C(F)C(NC=2C=C3NC(=O)C(F)(F)OC3=CC=2)=N1 QQTSKXIDHUIHDT-UHFFFAOYSA-N 0.000 claims description 2
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- RMTFEZUZAHJEFW-UHFFFAOYSA-N 5-fluoropyrimidine-2,4-diamine Chemical compound NC1=NC=C(F)C(N)=N1 RMTFEZUZAHJEFW-UHFFFAOYSA-N 0.000 claims description 2
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- VFXLHWFTRXBCJM-UHFFFAOYSA-N methyl 4-[4-[[2-(cyclobutylamino)-5-fluoropyrimidin-4-yl]amino]phenyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCN1C(C=C1)=CC=C1NC1=NC(NC2CCC2)=NC=C1F VFXLHWFTRXBCJM-UHFFFAOYSA-N 0.000 claims description 2
- KURYQYDZXWCPCB-UHFFFAOYSA-N n-[4-[[2-(cyclopropylamino)-5-fluoropyrimidin-4-yl]amino]phenyl]-n-methylacetamide Chemical compound C1=CC(N(C(C)=O)C)=CC=C1NC1=NC(NC2CC2)=NC=C1F KURYQYDZXWCPCB-UHFFFAOYSA-N 0.000 claims description 2
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- IWTHQBZXMOIXKI-AWEZNQCLSA-N tert-butyl n-[[4-[[5-fluoro-4-[[(2s)-2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl]amino]pyrimidin-2-yl]amino]cyclohexa-2,4-dien-1-ylidene]methyl]carbamate Chemical compound O([C@H](C(NC1=C2)=O)C)C1=CC=C2NC(C(=CN=1)F)=NC=1NC1=CCC(=CNC(=O)OC(C)(C)C)C=C1 IWTHQBZXMOIXKI-AWEZNQCLSA-N 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000006664 (C1-C3) perfluoroalkyl group Chemical group 0.000 claims 2
- AJKPUNIYEMWTIL-UHFFFAOYSA-N 2-[5-[[4-[(2,2-difluoro-3-oxo-4H-1,4-benzoxazin-6-yl)amino]-5-fluoropyrimidin-2-yl]amino]-2-methylcyclohexa-1,5-dien-1-yl]oxy-N-methylacetamide Chemical compound CNC(=O)COC1=C(C)CCC(Nc2ncc(F)c(Nc3ccc4OC(F)(F)C(=O)Nc4c3)n2)=C1 AJKPUNIYEMWTIL-UHFFFAOYSA-N 0.000 claims 2
- PLVRZSLMWIQVQJ-UHFFFAOYSA-N 4-n-(3,3-dimethyl-2,4-dihydro-1,4-benzoxazin-6-yl)-5-fluoro-2-n-(1-methylindazol-6-yl)pyrimidine-2,4-diamine Chemical compound O1CC(C)(C)NC2=CC(NC=3C(F)=CN=C(N=3)NC3=CC=C4C=NN(C4=C3)C)=CC=C21 PLVRZSLMWIQVQJ-UHFFFAOYSA-N 0.000 claims 2
- JOJBOWRCLLHSSS-UHFFFAOYSA-N 4-n-(4-amino-2h-chromen-6-yl)-5-fluoro-2-n-(1h-indazol-6-yl)pyrimidine-2,4-diamine Chemical compound C1=C2C=NNC2=CC(NC=2N=C(C(=CN=2)F)NC2=CC=C3OCC=C(C3=C2)N)=C1 JOJBOWRCLLHSSS-UHFFFAOYSA-N 0.000 claims 2
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US10/631,029 US7517886B2 (en) | 2002-07-29 | 2003-07-29 | Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds |
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TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
CN1678321A (zh) * | 2002-07-29 | 2005-10-05 | 里格尔药品股份有限公司 | 用2,4-嘧啶二胺化合物治疗或者预防自体免疫性疾病的方法 |
US7504410B2 (en) * | 2002-11-28 | 2009-03-17 | Schering Aktiengesellschaft | Chk-, Pdk- and Akt-inhibitory pyrimidines, their production and use as pharmaceutical agents |
UA80767C2 (en) * | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
CL2004000303A1 (es) * | 2003-02-20 | 2005-04-08 | Tibotec Pharm Ltd | Compuestos derivados de pirimidinas y triazinas; proceso de preparacion; composicion farmaceutica; y su uso para inhibir la replicacion del vih. |
US7122542B2 (en) | 2003-07-30 | 2006-10-17 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds |
BRPI0412347A (pt) * | 2003-07-30 | 2006-09-05 | Cyclacel Ltd | 2-aminofenil-4-fenilpiridinas como inibidores de quinase |
JP4741491B2 (ja) * | 2003-08-07 | 2011-08-03 | ライジェル ファーマシューティカルズ, インコーポレイテッド | 抗増殖剤としての2,4−ピリミジンジアミン化合物および使用 |
JP4607879B2 (ja) * | 2003-08-15 | 2011-01-05 | ノバルティス アーゲー | 新生物疾患、炎症および免疫障害の処置に有用な2,4−ピリミジンジアミン |
AU2005231507B2 (en) | 2004-04-08 | 2012-03-01 | Targegen, Inc. | Benzotriazine inhibitors of kinases |
WO2005118544A2 (en) | 2004-05-18 | 2005-12-15 | Rigel Pharmaceuticals, Inc. | Cycloalkyl substituted pyrimidinediamine compounds and their uses |
WO2006024034A1 (en) | 2004-08-25 | 2006-03-02 | Targegen, Inc. | Heterocyclic compounds and methods of use |
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