EA024729B1 - Киназные ингибиторы - Google Patents
Киназные ингибиторы Download PDFInfo
- Publication number
- EA024729B1 EA024729B1 EA201290324A EA201290324A EA024729B1 EA 024729 B1 EA024729 B1 EA 024729B1 EA 201290324 A EA201290324 A EA 201290324A EA 201290324 A EA201290324 A EA 201290324A EA 024729 B1 EA024729 B1 EA 024729B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- methyl
- pyrrol
- pyrimidin
- fluoropyrimidin
- dimethylphenylamino
- Prior art date
Links
- 229940043355 kinase inhibitor Drugs 0.000 title abstract description 8
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 174
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 42
- 201000011510 cancer Diseases 0.000 claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 239000003085 diluting agent Substances 0.000 claims abstract description 8
- 239000003937 drug carrier Substances 0.000 claims abstract description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 5
- -1 C3-C12 cycloalkyl Chemical group 0.000 claims description 226
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 120
- 201000010099 disease Diseases 0.000 claims description 88
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 88
- 229910052757 nitrogen Inorganic materials 0.000 claims description 67
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 64
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 54
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 230000001404 mediated effect Effects 0.000 claims description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- 125000005842 heteroatom Chemical group 0.000 claims description 35
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 35
- 229920006395 saturated elastomer Polymers 0.000 claims description 33
- 102000001253 Protein Kinase Human genes 0.000 claims description 32
- 108060006633 protein kinase Proteins 0.000 claims description 32
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 125000002541 furyl group Chemical group 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 239000013256 coordination polymer Substances 0.000 claims description 18
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 150000003462 sulfoxides Chemical class 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 10
- 229910052700 potassium Inorganic materials 0.000 claims description 10
- ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 8
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 102100026888 Mitogen-activated protein kinase kinase kinase 7 Human genes 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 108091008743 testicular receptors 4 Proteins 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 229950010765 pivalate Drugs 0.000 claims description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
- XAXIEMHZTRILQF-UHFFFAOYSA-N 2-[[1-[2-(3,5-dimethylanilino)-5-fluoropyrimidin-4-yl]-3-methylpyrazol-4-yl]methylamino]ethanol Chemical compound C1=C(CNCCO)C(C)=NN1C1=NC(NC=2C=C(C)C=C(C)C=2)=NC=C1F XAXIEMHZTRILQF-UHFFFAOYSA-N 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- NQVOVOHDIKUYAG-UHFFFAOYSA-N 1-[2-(3,5-dimethylanilino)pyrimidin-4-yl]-3-methylpyrazole-4-carboxylic acid Chemical compound C1=C(C(O)=O)C(C)=NN1C1=CC=NC(NC=2C=C(C)C=C(C)C=2)=N1 NQVOVOHDIKUYAG-UHFFFAOYSA-N 0.000 claims description 2
- SJEOYDLPQUJSER-UHFFFAOYSA-N 2-[4-[[4-[3-[(dimethylamino)methyl]-4-methylpyrrol-1-yl]-5-methylpyrimidin-2-yl]amino]-2,6-dimethylphenoxy]ethanol Chemical compound C1=C(C)C(CN(C)C)=CN1C1=NC(NC=2C=C(C)C(OCCO)=C(C)C=2)=NC=C1C SJEOYDLPQUJSER-UHFFFAOYSA-N 0.000 claims description 2
- ZZILMEKMXGZKEX-UHFFFAOYSA-N 2-[4-[[4-methyl-1-[5-methyl-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]pyrrol-3-yl]methyl]piperazin-1-yl]ethanol Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C(C)=CN=2)N2C=C(CN3CCN(CCO)CC3)C(C)=C2)=C1 ZZILMEKMXGZKEX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 102100034368 Potassium voltage-gated channel subfamily A member 1 Human genes 0.000 claims description 2
- 101710154114 Potassium voltage-gated channel subfamily A member 1 Proteins 0.000 claims description 2
- ZHVWWWSMWGZZKX-UHFFFAOYSA-N [1-[2-(3,5-dimethylanilino)-5-fluoropyrimidin-4-yl]-3-methylpyrazol-4-yl]methanol Chemical compound C1=C(CO)C(C)=NN1C1=NC(NC=2C=C(C)C=C(C)C=2)=NC=C1F ZHVWWWSMWGZZKX-UHFFFAOYSA-N 0.000 claims description 2
- SNZHQCIBLWFKIT-UHFFFAOYSA-N [4-methyl-1-[5-methyl-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]pyrrol-3-yl]methanol Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C(C)=CN=2)N2C=C(CO)C(C)=C2)=C1 SNZHQCIBLWFKIT-UHFFFAOYSA-N 0.000 claims description 2
- 230000005907 cancer growth Effects 0.000 claims description 2
- 210000005069 ears Anatomy 0.000 claims description 2
- KHPPMZICHKGGAL-UHFFFAOYSA-N ethyl 1-[2-(3,5-dimethylanilino)pyrimidin-4-yl]-3-methylpyrazole-4-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CN1C1=CC=NC(NC=2C=C(C)C=C(C)C=2)=N1 KHPPMZICHKGGAL-UHFFFAOYSA-N 0.000 claims description 2
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 2
- JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 claims description 2
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 2
- GWDHXJLNAVEBQS-UHFFFAOYSA-N Cl.Cl.Cl.N1=C(N=CC=C1)N Chemical compound Cl.Cl.Cl.N1=C(N=CC=C1)N GWDHXJLNAVEBQS-UHFFFAOYSA-N 0.000 claims 2
- ZATGKRCEPPRZRL-UHFFFAOYSA-N 1-[[1-[2-(2,3-dihydro-1h-inden-5-ylamino)pyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]azetidin-3-ol Chemical compound CC1=CN(C=2N=C(NC=3C=C4CCCC4=CC=3)N=CC=2)C=C1CN1CC(O)C1 ZATGKRCEPPRZRL-UHFFFAOYSA-N 0.000 claims 1
- ISDKZDUGCUIIRW-UHFFFAOYSA-N 1-[[1-[2-(3,5-dimethoxy-4-phenylmethoxyanilino)-5-methylpyrimidin-4-yl]pyrrol-3-yl]methyl]azetidin-3-ol Chemical compound C=1C(OC)=C(OCC=2C=CC=CC=2)C(OC)=CC=1NC(N=1)=NC=C(C)C=1N(C=1)C=CC=1CN1CC(O)C1 ISDKZDUGCUIIRW-UHFFFAOYSA-N 0.000 claims 1
- CEWDMUSFPREMTN-UHFFFAOYSA-N 1-[[1-[2-(3,5-dimethoxyanilino)-5-fluoropyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]piperidin-4-ol Chemical compound COC1=CC(OC)=CC(NC=2N=C(C(F)=CN=2)N2C=C(CN3CCC(O)CC3)C(C)=C2)=C1 CEWDMUSFPREMTN-UHFFFAOYSA-N 0.000 claims 1
- PEHATVLTXRELKI-UHFFFAOYSA-N 1-[[1-[2-(3,5-dimethylanilino)-5-fluoropyrimidin-4-yl]-3-methylpyrazol-4-yl]methyl]piperidin-4-ol Chemical compound CC1=NN(C=2C(=CN=C(NC=3C=C(C)C=C(C)C=3)N=2)F)C=C1CN1CCC(O)CC1 PEHATVLTXRELKI-UHFFFAOYSA-N 0.000 claims 1
- RTQYLJBPAHAXPW-UHFFFAOYSA-N 1-[[1-[2-[3,5-bis(trifluoromethyl)anilino]-5-fluoropyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]piperidin-4-ol Chemical compound CC1=CN(C=2C(=CN=C(NC=3C=C(C=C(C=3)C(F)(F)F)C(F)(F)F)N=2)F)C=C1CN1CCC(O)CC1 RTQYLJBPAHAXPW-UHFFFAOYSA-N 0.000 claims 1
- ARSIMJJZYDHISP-UHFFFAOYSA-N 1-[[1-[2-[3,5-dimethyl-4-(2-pyrrolidin-1-ylethoxy)anilino]-5-methylpyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]azetidin-3-ol Chemical compound CC1=CN(C=2C(=CN=C(NC=3C=C(C)C(OCCN4CCCC4)=C(C)C=3)N=2)C)C=C1CN1CC(O)C1 ARSIMJJZYDHISP-UHFFFAOYSA-N 0.000 claims 1
- KBOXMEIXTPIOIE-UHFFFAOYSA-N 1-[[1-[5-chloro-2-(2,3-dihydro-1,4-benzodioxin-6-ylamino)pyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]azetidin-3-ol Chemical compound CC1=CN(C=2C(=CN=C(NC=3C=C4OCCOC4=CC=3)N=2)Cl)C=C1CN1CC(O)C1 KBOXMEIXTPIOIE-UHFFFAOYSA-N 0.000 claims 1
- CRQQAYZOLKPQRZ-UHFFFAOYSA-N 1-[[1-[5-chloro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]azetidin-3-ol Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C(Cl)=CN=2)N2C=C(CN3CC(O)C3)C(C)=C2)=C1 CRQQAYZOLKPQRZ-UHFFFAOYSA-N 0.000 claims 1
- CYLUHHQGTYMADN-UHFFFAOYSA-N 1-[[1-[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]-4-(furan-3-yl)pyrrol-3-yl]methyl]azetidin-3-ol Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C(F)=CN=2)N2C=C(C(CN3CC(O)C3)=C2)C2=COC=C2)=C1 CYLUHHQGTYMADN-UHFFFAOYSA-N 0.000 claims 1
- NLHRNSWKEOUBND-UHFFFAOYSA-N 1-[[1-[5-fluoro-2-(naphthalen-2-ylamino)pyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]azetidin-3-ol Chemical compound CC1=CN(C=2C(=CN=C(NC=3C=C4C=CC=CC4=CC=3)N=2)F)C=C1CN1CC(O)C1 NLHRNSWKEOUBND-UHFFFAOYSA-N 0.000 claims 1
- SSNCUUYJMQQMHT-UHFFFAOYSA-N 1-[[1-[5-fluoro-2-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]piperidin-4-ol Chemical compound CC1=CN(C=2C(=CN=C(NC=3C=C(C=CC=3)C(F)(F)F)N=2)F)C=C1CN1CCC(O)CC1 SSNCUUYJMQQMHT-UHFFFAOYSA-N 0.000 claims 1
- WBEBJKYHWWWDJR-UHFFFAOYSA-N 1-[[3-methyl-1-[5-methyl-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]pyrazol-4-yl]methyl]azetidin-3-ol Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C(C)=CN=2)N2N=C(C)C(CN3CC(O)C3)=C2)=C1 WBEBJKYHWWWDJR-UHFFFAOYSA-N 0.000 claims 1
- KZBAZWAWQWUVBG-UHFFFAOYSA-N 1-[[4-cyclopropyl-1-[2-(3,5-dimethylanilino)pyrimidin-4-yl]pyrrol-3-yl]methyl]azetidin-3-ol Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C=C(C(CN3CC(O)C3)=C2)C2CC2)=C1 KZBAZWAWQWUVBG-UHFFFAOYSA-N 0.000 claims 1
- UBVUHNLTWFRDMU-UHFFFAOYSA-N 1-[[4-methyl-1-[2-[(1-methylindol-5-yl)amino]pyrimidin-4-yl]pyrrol-3-yl]methyl]azetidin-3-ol Chemical compound CC1=CN(C=2N=C(NC=3C=C4C=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC(O)C1 UBVUHNLTWFRDMU-UHFFFAOYSA-N 0.000 claims 1
- KYWXRBNOYGGPIZ-UHFFFAOYSA-N 1-morpholin-4-ylethanone Chemical compound CC(=O)N1CCOCC1 KYWXRBNOYGGPIZ-UHFFFAOYSA-N 0.000 claims 1
- QAZLVTUPZYIOQR-UHFFFAOYSA-N 2-[4-[4-[[4-[3-(hydroxymethyl)-4-methylpyrrol-1-yl]-5-methylpyrimidin-2-yl]amino]-2-methylphenyl]piperazin-1-yl]ethanol Chemical compound C1=C(CO)C(C)=CN1C1=NC(NC=2C=C(C)C(N3CCN(CCO)CC3)=CC=2)=NC=C1C QAZLVTUPZYIOQR-UHFFFAOYSA-N 0.000 claims 1
- VEUPGYNVVUMJPB-UHFFFAOYSA-N 2-[4-[[1-[2-[4-[4-(2-hydroxyethyl)piperazin-1-yl]-3-methylanilino]-5-methylpyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]piperazin-1-yl]ethanol Chemical compound CC1=CN(C=2C(=CN=C(NC=3C=C(C)C(N4CCN(CCO)CC4)=CC=3)N=2)C)C=C1CN1CCN(CCO)CC1 VEUPGYNVVUMJPB-UHFFFAOYSA-N 0.000 claims 1
- CSFPCQGTIYXGCB-UHFFFAOYSA-N 2-[4-[[1-[5-chloro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]-4-methylpyrrol-3-yl]methyl]piperazin-1-yl]ethanol Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C(Cl)=CN=2)N2C=C(CN3CCN(CCO)CC3)C(C)=C2)=C1 CSFPCQGTIYXGCB-UHFFFAOYSA-N 0.000 claims 1
- DFHFNGJJBVRENX-UHFFFAOYSA-N 2-[4-[[4-[3-(hydroxymethyl)-4-methylpyrrol-1-yl]-5-methylpyrimidin-2-yl]amino]-2,6-dimethoxyphenoxy]ethanol Chemical compound COC1=C(OCCO)C(OC)=CC(NC=2N=C(C(C)=CN=2)N2C=C(CO)C(C)=C2)=C1 DFHFNGJJBVRENX-UHFFFAOYSA-N 0.000 claims 1
- SDPNUXRSQIXWRV-UHFFFAOYSA-N 2-[4-[[5-fluoro-4-[3-(hydroxymethyl)-4-methylpyrrol-1-yl]pyrimidin-2-yl]amino]-2,6-dimethylphenoxy]ethanol Chemical compound C1=C(CO)C(C)=CN1C1=NC(NC=2C=C(C)C(OCCO)=C(C)C=2)=NC=C1F SDPNUXRSQIXWRV-UHFFFAOYSA-N 0.000 claims 1
- QVFHPRLROKAQAU-UHFFFAOYSA-N 2-[4-[[5-fluoro-4-[3-[(3-hydroxyazetidin-1-yl)methyl]-4-methylpyrrol-1-yl]pyrimidin-2-yl]amino]-2,6-dimethylphenoxy]-1-pyrrolidin-1-ylethanone Chemical compound CC1=CN(C=2C(=CN=C(NC=3C=C(C)C(OCC(=O)N4CCCC4)=C(C)C=3)N=2)F)C=C1CN1CC(O)C1 QVFHPRLROKAQAU-UHFFFAOYSA-N 0.000 claims 1
- HOZSQPXRWPLAGP-UHFFFAOYSA-N 3-[1-[2-(3,5-dimethylanilino)-5-fluoropyrimidin-4-yl]-3-methylpyrazol-4-yl]propane-1,2-diamine Chemical compound C1=C(CC(N)CN)C(C)=NN1C1=NC(NC=2C=C(C)C=C(C)C=2)=NC=C1F HOZSQPXRWPLAGP-UHFFFAOYSA-N 0.000 claims 1
- CQLCZFQSVHTFCG-UHFFFAOYSA-N 3-[4-[[4-methyl-1-[5-methyl-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]pyrrol-3-yl]methyl]piperazin-1-yl]-3-oxopropanenitrile Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C(C)=CN=2)N2C=C(CN3CCN(CC3)C(=O)CC#N)C(C)=C2)=C1 CQLCZFQSVHTFCG-UHFFFAOYSA-N 0.000 claims 1
- AAIDRPZSSAIFEU-UHFFFAOYSA-N 4-(3,5-dimethylphenyl)-5-fluoropyrimidin-2-amine Chemical compound CC1=CC(C)=CC(C=2C(=CN=C(N)N=2)F)=C1 AAIDRPZSSAIFEU-UHFFFAOYSA-N 0.000 claims 1
- LVCBSDNAOLXBRA-UHFFFAOYSA-N 4-[4-[(cyclohexylamino)methyl]-3-methylpyrazol-1-yl]-n-(3,5-dimethylphenyl)-5-fluoropyrimidin-2-amine Chemical compound CC1=NN(C=2C(=CN=C(NC=3C=C(C)C=C(C)C=3)N=2)F)C=C1CNC1CCCCC1 LVCBSDNAOLXBRA-UHFFFAOYSA-N 0.000 claims 1
- FDMMRQLYPWUWLO-UHFFFAOYSA-N [1-[2-(2,3-dihydro-1h-inden-5-ylamino)pyrimidin-4-yl]pyrrol-3-yl]methanol Chemical compound C1=C(CO)C=CN1C1=CC=NC(NC=2C=C3CCCC3=CC=2)=N1 FDMMRQLYPWUWLO-UHFFFAOYSA-N 0.000 claims 1
- OFBMORSMHMQDEK-UHFFFAOYSA-N [1-[2-(3,5-dimethoxyanilino)-5-fluoropyrimidin-4-yl]-3-methylpyrazol-4-yl]methanol Chemical compound COC1=CC(OC)=CC(NC=2N=C(C(F)=CN=2)N2N=C(C)C(CO)=C2)=C1 OFBMORSMHMQDEK-UHFFFAOYSA-N 0.000 claims 1
- YIZPCRJFBQPRAZ-UHFFFAOYSA-N [1-[2-(3,5-dimethoxyanilino)-5-fluoropyrimidin-4-yl]-4-methylpyrrol-3-yl]methanol Chemical compound COC1=CC(OC)=CC(NC=2N=C(C(F)=CN=2)N2C=C(CO)C(C)=C2)=C1 YIZPCRJFBQPRAZ-UHFFFAOYSA-N 0.000 claims 1
- DUNWFQSFQOCCLL-UHFFFAOYSA-N [1-[2-(3,5-dimethoxyanilino)-5-fluoropyrimidin-4-yl]pyrazol-4-yl]methanol Chemical compound COC1=CC(OC)=CC(NC=2N=C(C(F)=CN=2)N2N=CC(CO)=C2)=C1 DUNWFQSFQOCCLL-UHFFFAOYSA-N 0.000 claims 1
- JJAQKABFPOWJHJ-UHFFFAOYSA-N [1-[2-(3,5-dimethyl-4-phenoxyanilino)pyrimidin-4-yl]-4-methylpyrrol-3-yl]methanol Chemical compound C1=C(CO)C(C)=CN1C1=CC=NC(NC=2C=C(C)C(OC=3C=CC=CC=3)=C(C)C=2)=N1 JJAQKABFPOWJHJ-UHFFFAOYSA-N 0.000 claims 1
- NADOBMYCKJYASY-UHFFFAOYSA-N [1-[2-(3,5-dimethylanilino)-5-(trifluoromethyl)pyrimidin-4-yl]-4-methylpyrrol-3-yl]methanol Chemical compound C1=C(CO)C(C)=CN1C1=NC(NC=2C=C(C)C=C(C)C=2)=NC=C1C(F)(F)F NADOBMYCKJYASY-UHFFFAOYSA-N 0.000 claims 1
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| RU2727700C2 (ru) * | 2014-10-13 | 2020-07-23 | Юхан Корпорейшн | Соединения и композиции для модуляции киназной активности мутантов egfr |
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| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| WO2014110574A1 (en) | 2013-01-14 | 2014-07-17 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as pim kinase inhibitors |
| RS60244B1 (sr) | 2013-01-15 | 2020-06-30 | Incyte Holdings Corp | Jedinjenja tiazolkarboksamida i piridinkarboksamida korisna kao inhibitori pim kinaze |
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| CN104974091B (zh) * | 2014-04-10 | 2018-01-02 | 沈阳药科大学 | 3‑甲基‑1,5‑二芳基吡唑类化合物及其制备方法和用途 |
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| KR101633722B1 (ko) * | 2014-10-08 | 2016-06-28 | 한국화학연구원 | 4-(1-퍼롤-3,4-디카르복시아미드)피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물 |
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| CN104788427B (zh) * | 2015-02-05 | 2017-05-31 | 上海泓博智源医药股份有限公司 | 3‑(2‑嘧啶氨基)苯基丙烯酰胺类化合物及其应用 |
| WO2016127074A1 (en) | 2015-02-06 | 2016-08-11 | Blueprint Medicines Corporation | 2-(pyridin-3-yl)-pyrimidine derivatives as ret inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| SG10201913036RA (en) | 2015-02-20 | 2020-02-27 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
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| AR105967A1 (es) | 2015-09-09 | 2017-11-29 | Incyte Corp | Sales de un inhibidor de pim quinasa |
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| EA201290324A1 (ru) | 2012-12-28 |
| AU2010319382A1 (en) | 2012-04-19 |
| CA2780892A1 (en) | 2011-05-19 |
| EP2498607A1 (en) | 2012-09-19 |
| MX2012005332A (es) | 2012-10-15 |
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| US8629132B2 (en) | 2014-01-14 |
| ZA201204246B (en) | 2013-09-25 |
| US20110281841A1 (en) | 2011-11-17 |
| KR20130006417A (ko) | 2013-01-16 |
| WO2011060295A1 (en) | 2011-05-19 |
| BR112012011287A2 (pt) | 2020-09-01 |
| KR101663637B1 (ko) | 2016-10-07 |
| IL219726A0 (en) | 2012-07-31 |
| CL2012001221A1 (es) | 2013-06-07 |
| MY160820A (en) | 2017-03-31 |
| CN102811619A (zh) | 2012-12-05 |
| CN102811619B (zh) | 2015-04-22 |
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