JP6891262B2 - 哺乳動物のチロシンキナーゼｒｏｒ１活性の阻害剤として有用な２−フェニルイミダゾ［４，５−ｂ］ピリジン−７−アミン誘導体 - Google Patents
哺乳動物のチロシンキナーゼｒｏｒ１活性の阻害剤として有用な２−フェニルイミダゾ［４，５−ｂ］ピリジン−７−アミン誘導体 Download PDFInfo
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- JP6891262B2 JP6891262B2 JP2019500778A JP2019500778A JP6891262B2 JP 6891262 B2 JP6891262 B2 JP 6891262B2 JP 2019500778 A JP2019500778 A JP 2019500778A JP 2019500778 A JP2019500778 A JP 2019500778A JP 6891262 B2 JP6891262 B2 JP 6891262B2
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- phenyl
- imidazole
- pyridine
- amine
- chloro
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- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 title description 43
- 230000000694 effects Effects 0.000 title description 13
- 239000003112 inhibitor Substances 0.000 title description 5
- ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 2-phenyl-1h-imidazole Chemical compound C1=CNC(C=2C=CC=CC=2)=N1 ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 0.000 title description 3
- -1 6-Bromo-2- [4- (4-methylpiperazin-1-yl) phenyl] -N- (1-methylpiperidin-4-yl) -3H-imidazole Chemical compound 0.000 claims description 474
- 150000001875 compounds Chemical class 0.000 claims description 237
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 191
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 117
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 112
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 105
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 94
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 93
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 50
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 39
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 37
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- 125000005842 heteroatom Chemical group 0.000 claims description 33
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000002947 alkylene group Chemical group 0.000 claims description 30
- 125000004429 atom Chemical group 0.000 claims description 28
- 208000035475 disorder Diseases 0.000 claims description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 23
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 23
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 20
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims description 11
- 230000003463 hyperproliferative effect Effects 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 239000000654 additive Substances 0.000 claims description 8
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 5
- 230000000996 additive effect Effects 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 79
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims 18
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims 11
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 claims 6
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 4
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims 4
- YRGTWBPPKALYNE-UHFFFAOYSA-N 6-chloro-N-[1-[[4-(dimethylamino)phenyl]methyl]piperidin-4-yl]-2-[4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCOC)NC1CCN(CC1)CC1=CC=C(C=C1)N(C)C YRGTWBPPKALYNE-UHFFFAOYSA-N 0.000 claims 2
- 229960001867 guaiacol Drugs 0.000 claims 2
- KJCIMSSFGUGTGA-UHFFFAOYSA-N 1-methylpiperazin-2-one Chemical compound CN1CCNCC1=O KJCIMSSFGUGTGA-UHFFFAOYSA-N 0.000 claims 1
- CRNQLRKTYIIEDH-UHFFFAOYSA-N 2-[4-[4-[6-chloro-7-[[1-[(1,3,5-trimethylpyrazol-4-yl)methyl]piperidin-4-yl]amino]-1H-imidazo[4,5-b]pyridin-2-yl]phenyl]piperazin-1-yl]ethanol Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCO)NC1CCN(CC1)CC=1C(=NN(C=1C)C)C CRNQLRKTYIIEDH-UHFFFAOYSA-N 0.000 claims 1
- PJCOQQLLFPOOFJ-UHFFFAOYSA-N 4-[4-[6-chloro-7-[[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]amino]-1H-imidazo[4,5-b]pyridin-2-yl]phenyl]-1-(2-methoxyethyl)piperazin-2-one Chemical compound COCCN1CCN(CC1=O)c1ccc(cc1)-c1nc2ncc(Cl)c(NC3CCN(Cc4ccc(OC)cc4)CC3)c2[nH]1 PJCOQQLLFPOOFJ-UHFFFAOYSA-N 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- OHOIJCWXVDMYRE-UHFFFAOYSA-N 6-bromo-2-[4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCOC)NC1CC(N(C(C1)(C)C)C)(C)C OHOIJCWXVDMYRE-UHFFFAOYSA-N 0.000 claims 1
- TUXNALRLVXLNSS-UHFFFAOYSA-N 6-bromo-2-[4-[4-(3-methoxypropyl)piperazin-1-yl]phenyl]-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCCOC)NC1CC(N(C(C1)(C)C)C)(C)C TUXNALRLVXLNSS-UHFFFAOYSA-N 0.000 claims 1
- QUUKEKMXFARDHG-UHFFFAOYSA-N 6-bromo-2-[4-[4-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]piperazin-1-yl]phenyl]-N-(1-methylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CC=1C(=NOC=1C)C)NC1CCN(CC1)C QUUKEKMXFARDHG-UHFFFAOYSA-N 0.000 claims 1
- DEIPRSRSZCRSOM-UHFFFAOYSA-N 6-bromo-N-(1-methylpiperidin-4-yl)-2-[4-[2-methyl-4-(1,3-thiazol-2-ylmethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1C(CN(CC1)CC=1SC=CN=1)C)NC1CCN(CC1)C DEIPRSRSZCRSOM-UHFFFAOYSA-N 0.000 claims 1
- HDQUWJRQJWHCHD-UHFFFAOYSA-N 6-bromo-N-(1-methylpiperidin-4-yl)-2-[4-[3-methyl-4-(1,3-thiazol-2-ylmethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CC(N(CC1)CC=1SC=CN=1)C)NC1CCN(CC1)C HDQUWJRQJWHCHD-UHFFFAOYSA-N 0.000 claims 1
- WNRDZKAMANTMRY-SFHVURJKSA-N 6-bromo-N-[(3S)-1-methylpyrrolidin-3-yl]-2-[4-[4-(1,3-thiazol-2-ylmethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CC=1SC=CN=1)N[C@@H]1CN(CC1)C WNRDZKAMANTMRY-SFHVURJKSA-N 0.000 claims 1
- WLQHURZKKFEFGI-UHFFFAOYSA-N 6-bromo-N-[1-(cyclopropylmethyl)piperidin-4-yl]-2-[2-fluoro-4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=C(C=C(C=C1)N1CCN(CC1)CCOC)F)NC1CCN(CC1)CC1CC1 WLQHURZKKFEFGI-UHFFFAOYSA-N 0.000 claims 1
- AYRZKXFCDLHVGY-UHFFFAOYSA-N 6-bromo-N-[1-(cyclopropylmethyl)piperidin-4-yl]-2-[3-fluoro-4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC(=C(C=C1)N1CCN(CC1)CCOC)F)NC1CCN(CC1)CC1CC1 AYRZKXFCDLHVGY-UHFFFAOYSA-N 0.000 claims 1
- AYXPDJJSEQFNGL-UHFFFAOYSA-N 6-bromo-N-[1-(cyclopropylmethyl)piperidin-4-yl]-2-[3-methoxy-4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC(=C(C=C1)N1CCN(CC1)CCOC)OC)NC1CCN(CC1)CC1CC1 AYXPDJJSEQFNGL-UHFFFAOYSA-N 0.000 claims 1
- XPCNRBGALRRKAX-UHFFFAOYSA-N 6-bromo-N-[1-(cyclopropylmethyl)piperidin-4-yl]-2-[4-[4-(1,3-thiazol-2-ylmethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CC=1SC=CN=1)NC1CCN(CC1)CC1CC1 XPCNRBGALRRKAX-UHFFFAOYSA-N 0.000 claims 1
- XAGMWSTUPRQUOV-UHFFFAOYSA-N 6-bromo-N-[1-(cyclopropylmethyl)piperidin-4-yl]-2-[4-[4-[2-[(2-methylpyrazol-3-yl)amino]ethyl]piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound BrC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCNC1=CC=NN1C)NC1CCN(CC1)CC1CC1 XAGMWSTUPRQUOV-UHFFFAOYSA-N 0.000 claims 1
- QCLYKYCDAKNRBP-UHFFFAOYSA-N 6-chloro-2-(4-morpholin-4-ylphenyl)-N-[1-[(1,3,5-trimethylpyrazol-4-yl)methyl]piperidin-4-yl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCOCC1)NC1CCN(CC1)CC=1C(=NN(C=1C)C)C QCLYKYCDAKNRBP-UHFFFAOYSA-N 0.000 claims 1
- BXFYXRCOVANGBE-UHFFFAOYSA-N 6-chloro-2-[2-fluoro-4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-N-(1-propan-2-ylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=C(C=C(C=C1)N1CCN(CC1)CCOC)F)NC1CCN(CC1)C(C)C BXFYXRCOVANGBE-UHFFFAOYSA-N 0.000 claims 1
- QGJYCEGNRNUTPV-UHFFFAOYSA-N 6-chloro-2-[3-fluoro-4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-N-(1-propan-2-ylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC(=C(C=C1)N1CCN(CC1)CCOC)F)NC1CCN(CC1)C(C)C QGJYCEGNRNUTPV-UHFFFAOYSA-N 0.000 claims 1
- FOPXRLQWVIFZFN-UHFFFAOYSA-N 6-chloro-2-[3-methoxy-4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-N-(1-propan-2-ylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC(=C(C=C1)N1CCN(CC1)CCOC)OC)NC1CCN(CC1)C(C)C FOPXRLQWVIFZFN-UHFFFAOYSA-N 0.000 claims 1
- JYQQOORRDKFAQU-DEOSSOPVSA-N 6-chloro-2-[4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]-N-[(3S)-1-[(4-methoxyphenyl)methyl]pyrrolidin-3-yl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCOC)N[C@@H]1CN(CC1)CC1=CC=C(C=C1)OC JYQQOORRDKFAQU-DEOSSOPVSA-N 0.000 claims 1
- STJOEBXLGDGKAP-UHFFFAOYSA-N 6-chloro-2-[4-[4-(2-propan-2-yloxyethyl)piperazin-1-yl]phenyl]-N-(1-propan-2-ylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCOC(C)C)NC1CCN(CC1)C(C)C STJOEBXLGDGKAP-UHFFFAOYSA-N 0.000 claims 1
- PCNPZDABLPLKIT-UHFFFAOYSA-N 6-chloro-2-[4-[4-(3-methoxypropyl)piperazin-1-yl]phenyl]-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCCOC)NC1CC(N(C(C1)(C)C)C)(C)C PCNPZDABLPLKIT-UHFFFAOYSA-N 0.000 claims 1
- DNJVCLXOWCKKKD-UHFFFAOYSA-N 6-chloro-2-[4-[4-(4-methoxybutyl)piperazin-1-yl]phenyl]-N-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCCCOC)NC1CCN(CC1)CC1=CC=C(C=C1)OC DNJVCLXOWCKKKD-UHFFFAOYSA-N 0.000 claims 1
- WBNODXGGGWDMAM-UHFFFAOYSA-N 6-chloro-2-[4-[4-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]piperazin-1-yl]phenyl]-N-(1-methylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CC=1C(=NOC=1C)C)NC1CCN(CC1)C WBNODXGGGWDMAM-UHFFFAOYSA-N 0.000 claims 1
- LQHFHJJDBWROAT-UHFFFAOYSA-N 6-chloro-2-[4-[4-[(6-methylpyridin-3-yl)methyl]piperazin-1-yl]phenyl]-N-(1-propan-2-ylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CC=1C=NC(=CC=1)C)NC1CCN(CC1)C(C)C LQHFHJJDBWROAT-UHFFFAOYSA-N 0.000 claims 1
- IPXMTQJRYMJGMO-FQEVSTJZSA-N 6-chloro-2-[4-[4-[2-(2-methoxyethoxy)ethyl]piperazin-1-yl]phenyl]-N-[(3S)-1-methylpyrrolidin-3-yl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCOCCOC)N[C@@H]1CN(CC1)C IPXMTQJRYMJGMO-FQEVSTJZSA-N 0.000 claims 1
- RNBHSRVYLXYXRD-UHFFFAOYSA-N 6-chloro-2-[4-[4-[2-[(2-methylpyrazol-3-yl)amino]ethyl]piperazin-1-yl]phenyl]-N-(1-propan-2-ylpiperidin-4-yl)-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CCNC1=CC=NN1C)NC1CCN(CC1)C(C)C RNBHSRVYLXYXRD-UHFFFAOYSA-N 0.000 claims 1
- NQPWSWPGABSWMS-UHFFFAOYSA-N 6-chloro-N-(1-ethylpiperidin-4-yl)-2-[4-[3-methyl-4-(1,3-thiazol-2-ylmethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CC(N(CC1)CC=1SC=CN=1)C)NC1CCN(CC1)CC NQPWSWPGABSWMS-UHFFFAOYSA-N 0.000 claims 1
- BAVQRSQJJOSUTI-UHFFFAOYSA-N 6-chloro-N-(1-methylpiperidin-4-yl)-2-[4-(4-methylsulfonylpiperazin-1-yl)phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)S(=O)(=O)C)NC1CCN(CC1)C BAVQRSQJJOSUTI-UHFFFAOYSA-N 0.000 claims 1
- OSXANEMXTYCZMN-UHFFFAOYSA-N 6-chloro-N-(1-methylpiperidin-4-yl)-2-[4-[2-methyl-4-(1,3-thiazol-2-ylmethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1C(CN(CC1)CC=1SC=CN=1)C)NC1CCN(CC1)C OSXANEMXTYCZMN-UHFFFAOYSA-N 0.000 claims 1
- AQXLRBHVMWPVJO-UHFFFAOYSA-N 6-chloro-N-(1-methylpiperidin-4-yl)-2-[4-[3-methyl-4-(1,3-thiazol-2-ylmethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CC(N(CC1)CC=1SC=CN=1)C)NC1CCN(CC1)C AQXLRBHVMWPVJO-UHFFFAOYSA-N 0.000 claims 1
- ZMJJHVNFLIVGNR-UHFFFAOYSA-N 6-chloro-N-(1-methylpiperidin-4-yl)-2-[4-[4-(pyridin-4-ylmethyl)piperazin-1-yl]phenyl]-1H-imidazo[4,5-b]pyridin-7-amine Chemical compound ClC=1C(=C2C(=NC=1)NC(=N2)C1=CC=C(C=C1)N1CCN(CC1)CC1=CC=NC=C1)NC1CCN(CC1)C ZMJJHVNFLIVGNR-UHFFFAOYSA-N 0.000 claims 1
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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| PCT/EP2017/067262 WO2018011138A1 (en) | 2016-07-11 | 2017-07-10 | 2-phenylimidazo[4,5-b]pyridin-7-amine derivates useful as inhibitors of mammalian tyrosine kinase ror1 activity |
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| GB201710838D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | Bispecific antibodies |
| GB201710836D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | ROR1 Car T-Cells |
| AU2019223215B2 (en) * | 2018-02-23 | 2022-09-15 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Novel inhibitors of bacterial glutaminyl cyclases for use in the treatment of periodontal and related diseases |
| CN112574176B (zh) * | 2019-09-27 | 2024-03-15 | 隆泰申医药科技(南京)有限公司 | 一种杂芳基类化合物及其应用 |
| JP7700218B2 (ja) * | 2020-09-17 | 2025-06-30 | 浙江海正薬業股▲ふん▼有限公司 | ピペラジン誘導体、その製造方法、およびその使用 |
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| SE0202462D0 (sv) * | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | Novel use |
| SE0202464D0 (sv) | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | Use of compounds |
| EP1833829A2 (en) | 2004-12-23 | 2007-09-19 | F. Hoffmann-Roche AG | Benzamide substituted imidazo- and pyrrolo-pyridines as protein kinase inhibitors |
| WO2006066914A2 (en) | 2004-12-23 | 2006-06-29 | F. Hoffmann-La Roche Ag | Carbamate substituted imidazo- and pyrrolo-pyridines as protein kinase inhibitors |
| CA2596013C (en) | 2005-01-28 | 2012-06-05 | Daewoong Pharmaceutical Co., Ltd. | Benzoimidazole derivatives and pharmaceutical composition comprising the same |
| US20110059941A1 (en) | 2005-05-24 | 2011-03-10 | Peter William Rodney Caulkett | 2-phenyl substituted imidazol [4,5b] pyridine/pyrazine and purine derivatives as glucokinase modulators |
| JP2007063225A (ja) | 2005-09-01 | 2007-03-15 | Takeda Chem Ind Ltd | イミダゾピリジン化合物 |
| JP5205276B2 (ja) | 2005-12-22 | 2013-06-05 | ジ インスティテュート オブ キャンサー リサーチ：ロイヤル キャンサー ホスピタル | 酵素阻害剤 |
| WO2007083978A1 (en) | 2006-01-23 | 2007-07-26 | Crystalgenomics, Inc. | Imidazopyridine derivatives inhibiting protein kinase activity, method for the preparation thereof and pharmaceutical composition containing same |
| WO2008121064A1 (en) | 2007-03-30 | 2008-10-09 | Astrazeneca Ab | New imidazo[4,5-b]pyridine-6-halo-7-aryl/heteroaryl compounds 705 |
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| WO2009001021A1 (en) | 2007-06-26 | 2008-12-31 | Chroma Therapeutics Ltd. | Imidazopyridine derivatives useful as enzyme inhibitors for the treatment of cell proliferative and autoimmune diseases |
| CA2716947A1 (en) | 2008-02-29 | 2009-09-11 | Array Biopharma Inc. | Imidazo [4,5-b] pyridine derivatives used as raf inhibitors |
| US20120295915A1 (en) | 2009-11-24 | 2012-11-22 | Chaudhari Amita M | Azabenzimidazoles as fatty acid synthase inhibitors |
| US9150647B2 (en) | 2009-12-18 | 2015-10-06 | Kancera Ab | Biological inhibitors of ROR1 capable of inducing cell death |
| KR20130076046A (ko) * | 2011-12-28 | 2013-07-08 | 한미약품 주식회사 | 타이로신 카이네이즈 억제 활성을 갖는 신규 이미다조피리딘 유도체 |
| EP2809671B1 (en) | 2012-01-30 | 2016-01-13 | Cephalon, Inc. | Imidazo [4, 5 - b]pyridine derivatives as alk and jak modulators for the treatment of proliferative disorders |
| CN104936963B (zh) * | 2012-11-20 | 2017-11-28 | 普罗齐纳斯有限公司 | 作为蛋白激酶抑制剂的硫醚衍生物 |
| AU2016214492B2 (en) * | 2015-02-02 | 2020-05-07 | Kancera Ab | 2-phenyl-3H-imidazo[4,5-b]pyridine derivates useful as inhibitors of mammalian tyrosine kinase ROR1activity |
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| US11008318B2 (en) | 2021-05-18 |
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| KR102466810B1 (ko) | 2022-11-11 |
| EP3481824A1 (en) | 2019-05-15 |
| WO2018011138A1 (en) | 2018-01-18 |
| CN109563092A (zh) | 2019-04-02 |
| JP2019520412A (ja) | 2019-07-18 |
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