RU2677667C2 - Соединения n-пирролидинилмочевины, n'-пиразолилмочевины, тиомочевины, гуанидина и цианогуанидина как ингибиторы киназы trka - Google Patents

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Publication number

RU2677667C2

RU2677667C2 RU2015122414A RU2015122414A RU2677667C2 RU 2677667 C2 RU2677667 C2 RU 2677667C2 RU 2015122414 A RU2015122414 A RU 2015122414A RU 2015122414 A RU2015122414 A RU 2015122414A RU 2677667 C2 RU2677667 C2 RU 2677667C2

Authority

RU

Russia

Prior art keywords

methyl

alkyl

phenyl

methoxyethyl

pyrrolidin

Prior art date

2012-11-13

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• 101150111783 NTRK1 gene Proteins 0.000 title claims abstract description 54
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims description 12
• -1 n'-pyrazolyl-urea Chemical compound 0.000 title description 112
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 title description 6
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title description 4
• 229940043355 kinase inhibitor Drugs 0.000 title description 4
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
• MZVRPCYUUFGMLJ-UHFFFAOYSA-N pyrrolidin-1-ylurea Chemical compound NC(=O)NN1CCCC1 MZVRPCYUUFGMLJ-UHFFFAOYSA-N 0.000 title description 3
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 title description 2
• QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical class NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 title description 2
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 256
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• 239000012634 fragment Substances 0.000 claims abstract description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 373
• 125000003545 alkoxy group Chemical group 0.000 claims description 90
• 238000000034 method Methods 0.000 claims description 82
• 229910052736 halogen Inorganic materials 0.000 claims description 62
• 150000002367 halogens Chemical class 0.000 claims description 62
• 241000124008 Mammalia Species 0.000 claims description 57
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
• 125000001424 substituent group Chemical group 0.000 claims description 42
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• 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
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• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
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• WAVNMMLXWLOSLR-SQJMNOBHSA-N 1-[(3s,4r)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl]-3-[4-methyl-5-(1-methyl-6-oxopyridazin-3-yl)-2-phenylpyrazol-3-yl]urea Chemical compound N([C@@H]1CN(C[C@H]1C=1C=C(F)C(F)=CC=1)CCOC)C(=O)NC1=C(C)C(C2=NN(C)C(=O)C=C2)=NN1C1=CC=CC=C1 WAVNMMLXWLOSLR-SQJMNOBHSA-N 0.000 claims description 2
• CERDWPHMJKWGLA-RPLLCQBOSA-N 1-[(3s,4r)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl]-3-[4-methyl-5-(2-methylpyridin-3-yl)-2-phenylpyrazol-3-yl]urea Chemical compound N([C@@H]1CN(C[C@H]1C=1C=C(F)C(F)=CC=1)CCOC)C(=O)NC1=C(C)C(C=2C(=NC=CC=2)C)=NN1C1=CC=CC=C1 CERDWPHMJKWGLA-RPLLCQBOSA-N 0.000 claims description 2
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• JJHKOIBJUOTVJS-JYFHCDHNSA-N 1-[(3s,4r)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl]-3-[5-(2-ethoxypyrimidin-5-yl)-4-methyl-2-phenylpyrazol-3-yl]urea Chemical compound C1=NC(OCC)=NC=C1C1=NN(C=2C=CC=CC=2)C(NC(=O)N[C@H]2[C@@H](CN(CCOC)C2)C=2C=C(F)C(F)=CC=2)=C1C JJHKOIBJUOTVJS-JYFHCDHNSA-N 0.000 claims description 2
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• LVFMSSMPAIQDMW-IZZNHLLZSA-N 1-[(3s,4r)-4-(3,5-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl]-3-[4-methyl-5-(2-methylpyrimidin-5-yl)-2-phenylpyrazol-3-yl]urea Chemical compound N([C@@H]1CN(C[C@H]1C=1C=C(F)C=C(F)C=1)CCOC)C(=O)NC1=C(C)C(C=2C=NC(C)=NC=2)=NN1C1=CC=CC=C1 LVFMSSMPAIQDMW-IZZNHLLZSA-N 0.000 claims description 2
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• LXKGUWLCGOGWNY-IZZNHLLZSA-N 1-[(3s,4r)-4-(3-chlorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl]-3-[4-methyl-5-(1-methyl-6-oxopyridin-3-yl)-2-phenylpyrazol-3-yl]urea Chemical compound N([C@@H]1CN(C[C@H]1C=1C=C(Cl)C=CC=1)CCOC)C(=O)NC1=C(C)C(C2=CN(C)C(=O)C=C2)=NN1C1=CC=CC=C1 LXKGUWLCGOGWNY-IZZNHLLZSA-N 0.000 claims description 2
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