PL210414B1 - Związek pirazolowy, kompozycja zawierająca ten związek i jego zastosowania - Google Patents
Związek pirazolowy, kompozycja zawierająca ten związek i jego zastosowaniaInfo
- Publication number
- PL210414B1 PL210414B1 PL363244A PL36324401A PL210414B1 PL 210414 B1 PL210414 B1 PL 210414B1 PL 363244 A PL363244 A PL 363244A PL 36324401 A PL36324401 A PL 36324401A PL 210414 B1 PL210414 B1 PL 210414B1
- Authority
- PL
- Poland
- Prior art keywords
- methyl
- amine
- pyrazol
- pyrimidin
- alkyl
- Prior art date
Links
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title abstract 2
- 239000003909 protein kinase inhibitor Substances 0.000 title abstract 2
- 150000003217 pyrazoles Chemical class 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 72
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 claims abstract description 31
- 201000010099 disease Diseases 0.000 claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 108090000461 Aurora Kinase A Proteins 0.000 claims abstract description 15
- 102100032311 Aurora kinase A Human genes 0.000 claims abstract description 14
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 10
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 claims abstract 3
- 238000000034 method Methods 0.000 claims description 72
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 61
- -1 Pyrazole compound Chemical class 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 26
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 6
- JUPXIGULOXFQHK-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methylsulfanyl]-6-(4-methylpiperazin-1-yl)-n-(5-methyl-1h-pyrazol-3-yl)pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1CSC1=NC(NC=2NN=C(C)C=2)=CC(N2CCN(C)CC2)=N1 JUPXIGULOXFQHK-UHFFFAOYSA-N 0.000 claims description 5
- UVFVPEIUGCVFRV-UHFFFAOYSA-N methyl 6-[(5-methyl-1h-pyrazol-3-yl)amino]-2-[4-(propanoylamino)phenyl]sulfanylpyrimidine-4-carboxylate Chemical compound C1=CC(NC(=O)CC)=CC=C1SC1=NC(NC=2NN=C(C)C=2)=CC(C(=O)OC)=N1 UVFVPEIUGCVFRV-UHFFFAOYSA-N 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- MPSNETNZTLYXIK-UHFFFAOYSA-N 2-[(3-chlorophenyl)methylsulfanyl]-6-(4-methylpiperazin-1-yl)-n-(5-methyl-1h-pyrazol-3-yl)pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=CC(NC=2NN=C(C)C=2)=NC(SCC=2C=C(Cl)C=CC=2)=N1 MPSNETNZTLYXIK-UHFFFAOYSA-N 0.000 claims description 4
- WOGTVCHVDBTSJN-UHFFFAOYSA-N 2-benzylsulfanyl-6-(4-methylpiperazin-1-yl)-n-(5-methyl-1h-pyrazol-3-yl)pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=CC(NC=2NN=C(C)C=2)=NC(SCC=2C=CC=CC=2)=N1 WOGTVCHVDBTSJN-UHFFFAOYSA-N 0.000 claims description 4
- RHCLBIQUEJRCEF-UHFFFAOYSA-N 2-benzylsulfanyl-n-(5-methyl-1h-pyrazol-3-yl)-6-morpholin-4-ylpyrimidin-4-amine Chemical compound N1N=C(C)C=C1NC1=CC(N2CCOCC2)=NC(SCC=2C=CC=CC=2)=N1 RHCLBIQUEJRCEF-UHFFFAOYSA-N 0.000 claims description 4
- FYAPZIAUATWNOR-UHFFFAOYSA-N 3-methyl-n-[4-[4-[(5-methyl-1h-pyrazol-3-yl)amino]-6-phenylpyrimidin-2-yl]sulfanylphenyl]butanamide Chemical compound C1=CC(NC(=O)CC(C)C)=CC=C1SC1=NC(NC=2NN=C(C)C=2)=CC(C=2C=CC=CC=2)=N1 FYAPZIAUATWNOR-UHFFFAOYSA-N 0.000 claims description 4
- QOEQKXHMJLFYIS-UHFFFAOYSA-N 6-(4-methylpiperazin-1-yl)-n-(5-methyl-1h-pyrazol-3-yl)-2-[(4-morpholin-4-ylsulfonylphenyl)methylsulfanyl]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=CC(NC2=NNC(C)=C2)=NC(SCC=2C=CC(=CC=2)S(=O)(=O)N2CCOCC2)=N1 QOEQKXHMJLFYIS-UHFFFAOYSA-N 0.000 claims description 4
- HYUQZXHOCHTJGO-UHFFFAOYSA-N 6-n-(2-methoxyethyl)-4-n-(5-methyl-1h-pyrazol-3-yl)-2-[(4-morpholin-4-ylsulfonylphenyl)methylsulfanyl]pyrimidine-4,6-diamine Chemical compound N=1C(SCC=2C=CC(=CC=2)S(=O)(=O)N2CCOCC2)=NC(NCCOC)=CC=1NC=1C=C(C)NN=1 HYUQZXHOCHTJGO-UHFFFAOYSA-N 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- FJIJAWAHGQDWTR-UHFFFAOYSA-N methyl 4-[4-(methoxymethyl)-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylbenzoate Chemical compound N=1C(SC=2C=CC(=CC=2)C(=O)OC)=NC(COC)=CC=1NC1=CC(C)=NN1 FJIJAWAHGQDWTR-UHFFFAOYSA-N 0.000 claims description 4
- OWLHUABMKOEDDP-UHFFFAOYSA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-2-naphthalen-2-ylsulfanylpyrimidin-4-amine Chemical compound C1CC1C1=NNC(NC=2N=C(SC=3C=C4C=CC=CC4=CC=3)N=CC=2)=C1 OWLHUABMKOEDDP-UHFFFAOYSA-N 0.000 claims description 4
- QDLGURJHMBLUKW-UHFFFAOYSA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-5-methyl-2-naphthalen-2-ylsulfanylpyrimidin-4-amine Chemical compound CC1=CN=C(SC=2C=C3C=CC=CC3=CC=2)N=C1NC(NN=1)=CC=1C1CC1 QDLGURJHMBLUKW-UHFFFAOYSA-N 0.000 claims description 4
- BFCHWQNHLLJQKU-UHFFFAOYSA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-naphthalen-2-ylsulfanylpyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=CC(NC=2NN=C(C=2)C2CC2)=NC(SC=2C=C3C=CC=CC3=CC=2)=N1 BFCHWQNHLLJQKU-UHFFFAOYSA-N 0.000 claims description 4
- KXOKAYKGTCLIPO-UHFFFAOYSA-N n-(5-methyl-1h-pyrazol-3-yl)-2-naphthalen-2-ylsulfanyl-6-phenylpyrimidin-4-amine Chemical compound N1N=C(C)C=C1NC1=CC(C=2C=CC=CC=2)=NC(SC=2C=C3C=CC=CC3=CC=2)=N1 KXOKAYKGTCLIPO-UHFFFAOYSA-N 0.000 claims description 4
- RWEUEIUREFILDS-UHFFFAOYSA-N n-[4-[4-(4-methoxyphenyl)-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=CC(NC=2NN=C(C)C=2)=NC(SC=2C=CC(NC(C)=O)=CC=2)=N1 RWEUEIUREFILDS-UHFFFAOYSA-N 0.000 claims description 4
- WYIQXFOSEMJMAS-UHFFFAOYSA-N n-[4-[4-(hydroxymethyl)-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]propanamide Chemical compound C1=CC(NC(=O)CC)=CC=C1SC1=NC(CO)=CC(NC=2NN=C(C)C=2)=N1 WYIQXFOSEMJMAS-UHFFFAOYSA-N 0.000 claims description 4
- CJITVBOBWKKPLW-UHFFFAOYSA-N n-[4-[4-(methoxymethyl)-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]propanamide Chemical compound C1=CC(NC(=O)CC)=CC=C1SC1=NC(COC)=CC(NC=2NN=C(C)C=2)=N1 CJITVBOBWKKPLW-UHFFFAOYSA-N 0.000 claims description 4
- QUKPHHFZJNRUMP-UHFFFAOYSA-N n-[4-[4-[(5-cyclopropyl-1h-pyrazol-3-yl)amino]-6-phenylpyrimidin-2-yl]sulfanylphenyl]propanamide Chemical compound C1=CC(NC(=O)CC)=CC=C1SC1=NC(NC=2NN=C(C=2)C2CC2)=CC(C=2C=CC=CC=2)=N1 QUKPHHFZJNRUMP-UHFFFAOYSA-N 0.000 claims description 4
- GLXTXPWWOYBBCI-UHFFFAOYSA-N n-[4-[4-[(5-methyl-1h-pyrazol-3-yl)amino]-6-phenylpyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide Chemical compound N1N=C(C)C=C1NC1=CC(C=2C=CC=CC=2)=NC(SC=2C=CC(NC(=O)C3CC3)=CC=2)=N1 GLXTXPWWOYBBCI-UHFFFAOYSA-N 0.000 claims description 4
- FNBGPMNXEGPANM-UHFFFAOYSA-N n-[4-[4-[(5-methyl-1h-pyrazol-3-yl)amino]-6-phenylpyrimidin-2-yl]sulfanylphenyl]propanamide Chemical compound C1=CC(NC(=O)CC)=CC=C1SC1=NC(NC=2NN=C(C)C=2)=CC(C=2C=CC=CC=2)=N1 FNBGPMNXEGPANM-UHFFFAOYSA-N 0.000 claims description 4
- MNDVGQRXFSJZGA-UHFFFAOYSA-N n-[4-[4-[(5-methyl-1h-pyrazol-3-yl)amino]-6-phenylpyrimidin-2-yl]sulfanylphenyl]propane-2-sulfonamide Chemical compound C1=CC(NS(=O)(=O)C(C)C)=CC=C1SC1=NC(NC=2NN=C(C)C=2)=CC(C=2C=CC=CC=2)=N1 MNDVGQRXFSJZGA-UHFFFAOYSA-N 0.000 claims description 4
- BGNRYQCGVJJPRI-UHFFFAOYSA-N n-[4-[4-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1SC1=NC=CC(NC=2NN=C(C)C=2)=N1 BGNRYQCGVJJPRI-UHFFFAOYSA-N 0.000 claims description 4
- PPKYLKQWCYTYOP-UHFFFAOYSA-N n-[4-[4-[4-[3-(dimethylamino)propoxy]phenyl]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]acetamide Chemical compound C1=CC(OCCCN(C)C)=CC=C1C1=CC(NC=2NN=C(C)C=2)=NC(SC=2C=CC(NC(C)=O)=CC=2)=N1 PPKYLKQWCYTYOP-UHFFFAOYSA-N 0.000 claims description 4
- CXLPODKWPHSQEB-UHFFFAOYSA-N 2-(dimethylamino)-n-[4-[4-[(5-methyl-1h-pyrazol-3-yl)amino]-6-phenylpyrimidin-2-yl]sulfanylphenyl]acetamide Chemical compound C1=CC(NC(=O)CN(C)C)=CC=C1SC1=NC(NC=2NN=C(C)C=2)=CC(C=2C=CC=CC=2)=N1 CXLPODKWPHSQEB-UHFFFAOYSA-N 0.000 claims description 3
- XRAFMWYIOALWSA-UHFFFAOYSA-N 2-[(3,5-dimethoxyphenyl)methylsulfanyl]-n-(5-methyl-1h-pyrazol-3-yl)-6-pyrrolidin-3-ylpyrimidin-4-amine Chemical compound COC1=CC(OC)=CC(CSC=2N=C(C=C(NC=3NN=C(C)C=3)N=2)C2CNCC2)=C1 XRAFMWYIOALWSA-UHFFFAOYSA-N 0.000 claims description 3
- LUJIOOSJBZJHHK-UHFFFAOYSA-N 2-[(3-chlorophenyl)methylsulfanyl]-6-n-(2-methoxyethyl)-4-n-(5-methyl-1h-pyrazol-3-yl)pyrimidine-4,6-diamine Chemical compound N=1C(SCC=2C=C(Cl)C=CC=2)=NC(NCCOC)=CC=1NC1=CC(C)=NN1 LUJIOOSJBZJHHK-UHFFFAOYSA-N 0.000 claims description 3
- VWRGZMRMYRYZGQ-UHFFFAOYSA-N 2-[(3-chlorophenyl)methylsulfanyl]-n-(5-methyl-1h-pyrazol-3-yl)-6-morpholin-4-ylpyrimidin-4-amine Chemical compound N1N=C(C)C=C1NC1=CC(N2CCOCC2)=NC(SCC=2C=C(Cl)C=CC=2)=N1 VWRGZMRMYRYZGQ-UHFFFAOYSA-N 0.000 claims description 3
- AIRMEXFVLJJUJE-UHFFFAOYSA-N 6-(2-methylphenyl)-n-(5-methyl-1h-pyrazol-3-yl)-2-naphthalen-2-ylsulfanylpyrimidin-4-amine Chemical compound N1N=C(C)C=C1NC1=CC(C=2C(=CC=CC=2)C)=NC(SC=2C=C3C=CC=CC3=CC=2)=N1 AIRMEXFVLJJUJE-UHFFFAOYSA-N 0.000 claims description 3
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| US6660731B2 (en) | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| ES2307667T3 (es) * | 2000-12-05 | 2008-12-01 | Vertex Pharmaceuticals Incorporated | Inhibidires de quinasas terminales c-jun(jnk) y otras proteinas quinasas. |
| HUP0400639A3 (en) * | 2000-12-21 | 2010-03-29 | Vertex Pharma | Pyrazole compounds useful as protein kinase inhibitors and pharmaceutical compositions containing them |
| MXPA03008658A (es) * | 2001-03-23 | 2005-04-11 | Bayer Ag | Inhibidores de rho-cinasa. |
| ATE400274T1 (de) | 2001-04-10 | 2008-07-15 | Merck & Co Inc | Hemmstoffe der akt aktivität |
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| US7115617B2 (en) | 2001-08-22 | 2006-10-03 | Amgen Inc. | Amino-substituted pyrimidinyl derivatives and methods of use |
| US6939874B2 (en) | 2001-08-22 | 2005-09-06 | Amgen Inc. | Substituted pyrimidinyl derivatives and methods of use |
| WO2003026666A1 (en) * | 2001-09-26 | 2003-04-03 | Bayer Pharmaceuticals Corporation | 2-phenylamino-4- (5-pyrazolylamino)-pyrimidine derivatives as kinase inhibitors, in particular, as src kinase inhibitors |
| DE60238999D1 (de) * | 2001-09-26 | 2011-03-03 | Pfizer Italia Srl | Aminoindazolderivate mit kinaseinhibierender wirkung, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen |
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| JP4656838B2 (ja) * | 2002-02-06 | 2011-03-23 | バーテックス ファーマシューティカルズ インコーポレイテッド | Gsk−3の阻害剤として有用なヘテロアリール化合物 |
| WO2003078426A1 (en) * | 2002-03-15 | 2003-09-25 | Vertex Pharmaceuticals, Inc. | Azolylaminoazine as inhibitors of protein kinases |
| EP1485100B1 (en) * | 2002-03-15 | 2010-05-05 | Vertex Pharmaceuticals Incorporated | Azinylaminoazoles as inhibitors of protein kinases |
| EP1485380B1 (en) | 2002-03-15 | 2010-05-19 | Vertex Pharmaceuticals Incorporated | Azolylaminoazines as inhibitors of protein kinases |
| WO2003086394A1 (en) | 2002-04-08 | 2003-10-23 | Merck & Co., Inc. | Inhibitors of akt activity |
| WO2003104230A1 (ja) | 2002-06-07 | 2003-12-18 | 協和醱酵工業株式会社 | 二環性ピリミジン誘導体 |
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| AU2003261204A1 (en) * | 2002-07-23 | 2004-02-09 | Smithkline Beecham Corporation | Pyrazolopyrimidines as kinase inhibitors |
| CN103169708B (zh) | 2002-07-29 | 2018-02-02 | 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 |
| PL374967A1 (en) | 2002-08-02 | 2005-11-14 | Vertex Pharmaceuticals Incorporated | Pyrazole compositions useful as inhibitors of gsk-3 |
| SI1532145T1 (sl) * | 2002-08-02 | 2007-02-28 | Vertex Pharma | Pirazolni sestavki, koristni kot inhibitorji GSK-3 |
| AU2003278249B8 (en) | 2002-09-05 | 2010-11-18 | Aventis Pharma S.A. | Novel aminoindazole derivatives as medicines and pharmaceutical compositions containing same |
| FR2844267B1 (fr) * | 2002-09-05 | 2008-02-15 | Aventis Pharma Sa | Nouveaux derives d'aminoindazoles a titre de medicaments et compositions pharmaceutiques les renfermant |
| AU2003255482A1 (en) * | 2002-10-02 | 2004-04-23 | Merck Patent Gmbh | Use of 4 amino-quinazolines as anti cancer agents |
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