KR20070107024A - 신규 피리딘 화합물 - Google Patents

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Publication number

KR20070107024A

KR20070107024A KR1020077018077A KR20077018077A KR20070107024A KR 20070107024 A KR20070107024 A KR 20070107024A KR 1020077018077 A KR1020077018077 A KR 1020077018077A KR 20077018077 A KR20077018077 A KR 20077018077A KR 20070107024 A KR20070107024 A KR 20070107024A

Authority

KR

South Korea

Prior art keywords

aryl

heterocyclyl

amino

ethyl

cycloalkyl

Prior art date

2005-01-06

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

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• -1 pyridine compound Chemical class 0.000 title claims description 332
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims description 25
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title claims description 13
• 150000001875 compounds Chemical class 0.000 claims abstract description 249
• 238000000034 method Methods 0.000 claims abstract description 43
• 239000003814 drug Substances 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• 125000003118 aryl group Chemical group 0.000 claims description 334
• 125000000623 heterocyclic group Chemical group 0.000 claims description 329
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 187
• 229910052736 halogen Inorganic materials 0.000 claims description 134
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 133
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 121
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 120
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 117
• 229910052794 bromium Inorganic materials 0.000 claims description 116
• 229910052801 chlorine Inorganic materials 0.000 claims description 116
• 229910052731 fluorine Inorganic materials 0.000 claims description 116
• 229910052740 iodine Inorganic materials 0.000 claims description 116
• 150000002367 halogens Chemical class 0.000 claims description 114
• 229910052760 oxygen Inorganic materials 0.000 claims description 112
• 239000001301 oxygen Substances 0.000 claims description 112
• 229910052757 nitrogen Inorganic materials 0.000 claims description 111
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 108
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 107
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 106
• 125000004414 alkyl thio group Chemical group 0.000 claims description 105
• 125000004429 atom Chemical group 0.000 claims description 105
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 101
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 78
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 78
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 78
• 229910052739 hydrogen Inorganic materials 0.000 claims description 59
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 54
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 51
• 125000005110 aryl thio group Chemical group 0.000 claims description 51
• 125000004122 cyclic group Chemical group 0.000 claims description 50
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 50
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 44
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 40
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 39
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 39
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 39
• 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 34
• 229910052799 carbon Inorganic materials 0.000 claims description 29
• 125000005843 halogen group Chemical group 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 26
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 24
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 24
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
• DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims description 20
• 229960001238 methylnicotinate Drugs 0.000 claims description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims description 17
• 125000001424 substituent group Chemical group 0.000 claims description 17
• 125000005842 heteroatom Chemical group 0.000 claims description 16
• IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical compound NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 claims description 16
• 235000001968 nicotinic acid Nutrition 0.000 claims description 15
• 239000011664 nicotinic acid Substances 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 12
• 230000015572 biosynthetic process Effects 0.000 claims description 11
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 10
• 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• 239000011593 sulfur Substances 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• UBLUZXPVNMESOL-UHFFFAOYSA-N ethyl 6-[3-(benzenesulfonylcarbamoylamino)azetidin-1-yl]-5-chloropyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CC(NC(=O)NS(=O)(=O)C=2C=CC=CC=2)C1 UBLUZXPVNMESOL-UHFFFAOYSA-N 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 238000003786 synthesis reaction Methods 0.000 claims description 9
• 239000000543 intermediate Substances 0.000 claims description 8
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
• 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 8
• 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 8
• 238000011282 treatment Methods 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 125000002950 monocyclic group Chemical group 0.000 claims description 7
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
• 125000002619 bicyclic group Chemical group 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 6
• 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 5
• INWVOWWBLBBQBZ-UHFFFAOYSA-N ethyl 5-chloro-6-[4-[(2-methylphenyl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)CC1 INWVOWWBLBBQBZ-UHFFFAOYSA-N 0.000 claims description 5
• USFSMRAJQUFCNV-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-fluorophenyl)sulfonylcarbamoyl]piperazin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC(F)=CC=2)CC1 USFSMRAJQUFCNV-UHFFFAOYSA-N 0.000 claims description 5
• KRICGQWFOCXJGJ-UHFFFAOYSA-N ethyl 6-[4-(benzenesulfonylcarbamoyl)-3-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]piperazin-1-yl]-5-chloropyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CC(CCC(=O)OC(C)(C)C)N(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 KRICGQWFOCXJGJ-UHFFFAOYSA-N 0.000 claims description 5
• XAQZFANMDXCKCF-UHFFFAOYSA-N ethyl 6-[4-(benzenesulfonylcarbamoyl)-3-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]piperazin-1-yl]-5-cyano-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(CCC(=O)OC(C)(C)C)N(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 XAQZFANMDXCKCF-UHFFFAOYSA-N 0.000 claims description 5
• HZWVJSZPVJHIRF-UHFFFAOYSA-N ethyl 6-[4-(benzenesulfonylcarbamoyl)piperazin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 HZWVJSZPVJHIRF-UHFFFAOYSA-N 0.000 claims description 5
• RBEPZLOCUMMCFC-UHFFFAOYSA-N ethyl 6-[4-(benzenesulfonylcarbamoylamino)piperidin-1-yl]-5-chloropyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCC(NC(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 RBEPZLOCUMMCFC-UHFFFAOYSA-N 0.000 claims description 5
• QPTUDBWQWSMCEA-UHFFFAOYSA-N ethyl 6-[4-[(4-chlorophenyl)sulfonylcarbamoyl]piperazin-1-yl]-5-cyano-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)CC1 QPTUDBWQWSMCEA-UHFFFAOYSA-N 0.000 claims description 5
• UIFRIEXMOTVTFS-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-3-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]piperazin-1-yl]-5-cyano-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(CCC(=O)OC(C)(C)C)N(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 UIFRIEXMOTVTFS-UHFFFAOYSA-N 0.000 claims description 5
• VHZYXGNZMRAFNP-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperazin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 VHZYXGNZMRAFNP-UHFFFAOYSA-N 0.000 claims description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
• 230000002401 inhibitory effect Effects 0.000 claims description 5
• XXFVNYOVKCSHGL-UHFFFAOYSA-N propan-2-yl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OC(C)C)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 XXFVNYOVKCSHGL-UHFFFAOYSA-N 0.000 claims description 5
• IUFLJCZIMLKGQN-UHFFFAOYSA-N 3-[1-(benzenesulfonylcarbamoyl)-4-[3-cyano-5-ethoxycarbonyl-6-(trifluoromethyl)pyridin-2-yl]piperazin-2-yl]propanoic acid Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(CCC(O)=O)N(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 IUFLJCZIMLKGQN-UHFFFAOYSA-N 0.000 claims description 4
• ICKIAJXQACGDGC-UHFFFAOYSA-N 3-[1-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-4-[3-cyano-5-[ethoxy(hydroxy)methyl]-6-(trifluoromethyl)pyridin-2-yl]piperazin-2-yl]propanoic acid Chemical compound N1=C(C(F)(F)F)C(C(O)OCC)=CC(C#N)=C1N1CC(CCC(O)=O)N(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 ICKIAJXQACGDGC-UHFFFAOYSA-N 0.000 claims description 4
• MMCYXMUZXDBPKB-UHFFFAOYSA-N 3-methylbutyl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCCC(C)C)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 MMCYXMUZXDBPKB-UHFFFAOYSA-N 0.000 claims description 4
• UQGABJOTOYVCCV-UHFFFAOYSA-N 4-[3-chloro-5-(5-ethyl-1,3-oxazol-2-yl)pyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylpiperazine-1-carboxamide Chemical compound O1C(CC)=CN=C1C(C=C1Cl)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 UQGABJOTOYVCCV-UHFFFAOYSA-N 0.000 claims description 4
• 239000002671 adjuvant Substances 0.000 claims description 4
• MXUMUFQZUKAXKE-UHFFFAOYSA-N butyl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCCCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 MXUMUFQZUKAXKE-UHFFFAOYSA-N 0.000 claims description 4
• 150000001721 carbon Chemical group 0.000 claims description 4
• 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims description 4
• BYJMWFVRKNECFT-UHFFFAOYSA-N ethyl 5-chloro-6-[3-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]pyrrolidin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 BYJMWFVRKNECFT-UHFFFAOYSA-N 0.000 claims description 4
• JBKZHGWLYHHCRD-UHFFFAOYSA-N ethyl 5-chloro-6-[4-[(4-chlorophenyl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)CC1 JBKZHGWLYHHCRD-UHFFFAOYSA-N 0.000 claims description 4
• LWUMYRAPPSSZQT-UHFFFAOYSA-N ethyl 5-chloro-6-[4-[(4-fluorophenyl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC(F)=CC=2)CC1 LWUMYRAPPSSZQT-UHFFFAOYSA-N 0.000 claims description 4
• PSJMJDNZFUDWHS-UHFFFAOYSA-N ethyl 5-chloro-6-[4-[(4-methylphenyl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC(C)=CC=2)CC1 PSJMJDNZFUDWHS-UHFFFAOYSA-N 0.000 claims description 4
• RQEHXCUFAJNTHP-UHFFFAOYSA-N ethyl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 RQEHXCUFAJNTHP-UHFFFAOYSA-N 0.000 claims description 4
• ATMSUCFFJIUPRV-UHFFFAOYSA-N ethyl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 ATMSUCFFJIUPRV-UHFFFAOYSA-N 0.000 claims description 4
• SXBLWMMNQDYGTG-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(2-methylphenyl)sulfonylcarbamoyl]piperazin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)CC1 SXBLWMMNQDYGTG-UHFFFAOYSA-N 0.000 claims description 4
• HWIBBJSFZYEVKI-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-methylphenyl)sulfonylcarbamoyl]piperazin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC(C)=CC=2)CC1 HWIBBJSFZYEVKI-UHFFFAOYSA-N 0.000 claims description 4
• PHZXEFQHQGATEP-UHFFFAOYSA-N ethyl 6-[4-(benzenesulfonylcarbamoyl)piperazin-1-yl]-5-chloropyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 PHZXEFQHQGATEP-UHFFFAOYSA-N 0.000 claims description 4
• QRBKIMPLBWIGHP-UHFFFAOYSA-N ethyl 6-[4-(benzenesulfonylcarbamoyl)piperidin-1-yl]-5-chloropyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 QRBKIMPLBWIGHP-UHFFFAOYSA-N 0.000 claims description 4
• MWNQODBRDGOPEN-UHFFFAOYSA-N ethyl 6-[4-[(2-chlorophenyl)sulfonylcarbamoyl]piperazin-1-yl]-5-cyano-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)Cl)CC1 MWNQODBRDGOPEN-UHFFFAOYSA-N 0.000 claims description 4
• NPPOKWMMVGLMKT-UHFFFAOYSA-N methyl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 NPPOKWMMVGLMKT-UHFFFAOYSA-N 0.000 claims description 4
• OKVOIJXNIGRZNY-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[3-chloro-5-(5-ethyl-1,3-oxazol-2-yl)pyridin-2-yl]piperazine-1-carboxamide Chemical compound O1C(CC)=CN=C1C(C=C1Cl)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 OKVOIJXNIGRZNY-UHFFFAOYSA-N 0.000 claims description 4
• XISVCAGCODBBBH-UHFFFAOYSA-N propyl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 XISVCAGCODBBBH-UHFFFAOYSA-N 0.000 claims description 4
• TUXQEPDPBKJWMS-UHFFFAOYSA-N 2,2-dimethylpropyl 6-[3-[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OCC(C)(C)C)C(C)=NC(N2CC(C2)NC(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)=C1C#N TUXQEPDPBKJWMS-UHFFFAOYSA-N 0.000 claims description 3
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• YPFCJBJMMACVBE-UHFFFAOYSA-N 3-[1-(benzenesulfonylcarbamoyl)-4-(3-chloro-5-ethoxycarbonylpyridin-2-yl)piperazin-2-yl]propanoic acid Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CC(CCC(O)=O)N(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 YPFCJBJMMACVBE-UHFFFAOYSA-N 0.000 claims description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
• JZUVWUCVDGUZFC-UHFFFAOYSA-N 4-[3-chloro-5-(5-methyl-1,3-oxazol-2-yl)pyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylpiperazine-1-carboxamide Chemical compound O1C(C)=CN=C1C(C=C1Cl)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 JZUVWUCVDGUZFC-UHFFFAOYSA-N 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
• PARBGNWIFVZWAN-UHFFFAOYSA-N ethyl 4-amino-5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=C(N)C(C(=O)OCC)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 PARBGNWIFVZWAN-UHFFFAOYSA-N 0.000 claims description 3
• ICIHBWFXUFQYTQ-UHFFFAOYSA-N ethyl 5-chloro-6-[4-[(2-chlorophenyl)sulfonylcarbamoyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)Cl)CC1 ICIHBWFXUFQYTQ-UHFFFAOYSA-N 0.000 claims description 3
• HZSOYWILVRWZFN-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,4-dichlorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C(=CC(Cl)=CC=2)Cl)C1 HZSOYWILVRWZFN-UHFFFAOYSA-N 0.000 claims description 3
• IDRBWZGCZZKPHJ-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,5-dimethylfuran-3-yl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C2=C(OC(C)=C2)C)C1 IDRBWZGCZZKPHJ-UHFFFAOYSA-N 0.000 claims description 3
• UTEGZDGSGWVSOL-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,5-dimethylthiophen-3-yl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C2=C(SC(C)=C2)C)C1 UTEGZDGSGWVSOL-UHFFFAOYSA-N 0.000 claims description 3
• FGWISMSMQQPUJZ-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-methoxyphenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=CC(OC)=CC=2)C1 FGWISMSMQQPUJZ-UHFFFAOYSA-N 0.000 claims description 3
• BPLBHGMLIYZDHX-UHFFFAOYSA-N ethyl 6-[3-[(3-bromophenyl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(Br)C=CC=2)C1 BPLBHGMLIYZDHX-UHFFFAOYSA-N 0.000 claims description 3
• UKLTWOHKSDYECL-UHFFFAOYSA-N ethyl 6-[3-[(3-chlorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(Cl)C=CC=2)C1 UKLTWOHKSDYECL-UHFFFAOYSA-N 0.000 claims description 3
• SFEMQHGKMZJZDT-UHFFFAOYSA-N ethyl 6-[3-[(4-chlorophenyl)sulfonylcarbamoylamino]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(NC(=O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)C1 SFEMQHGKMZJZDT-UHFFFAOYSA-N 0.000 claims description 3
• VKIAIPSYXFDGAT-UHFFFAOYSA-N ethyl 6-[3-[(5-bromothiophen-2-yl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2SC(Br)=CC=2)C1 VKIAIPSYXFDGAT-UHFFFAOYSA-N 0.000 claims description 3
• VUULCTWERJCIOD-UHFFFAOYSA-N ethyl 6-[3-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)C1 VUULCTWERJCIOD-UHFFFAOYSA-N 0.000 claims description 3
• DXRGSOKOVRDWNW-UHFFFAOYSA-N ethyl 6-[3-[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(NC(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)C1 DXRGSOKOVRDWNW-UHFFFAOYSA-N 0.000 claims description 3
• CILSRBUAKHLULT-UHFFFAOYSA-N ethyl 6-[3-[(5-chlorothiophen-3-yl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(Cl)SC=2)C1 CILSRBUAKHLULT-UHFFFAOYSA-N 0.000 claims description 3
• CSJGQSBCSQFHSP-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-2-methylpiperazin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1C(C)CN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 CSJGQSBCSQFHSP-UHFFFAOYSA-N 0.000 claims description 3
• CFTMMJHRAWMXEM-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-ethylpyridine-3-carboxylate Chemical compound N1=C(CC)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 CFTMMJHRAWMXEM-UHFFFAOYSA-N 0.000 claims description 3
• YVEPQWPFZNTAAE-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 YVEPQWPFZNTAAE-UHFFFAOYSA-N 0.000 claims description 3
• XPUHLVFTFLMVKI-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-propan-2-ylpyridine-3-carboxylate Chemical compound N1=C(C(C)C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 XPUHLVFTFLMVKI-UHFFFAOYSA-N 0.000 claims description 3
• GFVMYYVRTZJDHI-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(NC(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 GFVMYYVRTZJDHI-UHFFFAOYSA-N 0.000 claims description 3
• FLCWYHVLJNVKMZ-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-3-yl)sulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=C(Cl)SC=2)CC1 FLCWYHVLJNVKMZ-UHFFFAOYSA-N 0.000 claims description 3
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 3
• 125000001072 heteroaryl group Chemical group 0.000 claims description 3
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 3
• UACQSHPMVFGLEW-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[3-chloro-5-(5-ethyl-4,5-dihydro-1,3-oxazol-2-yl)pyridin-2-yl]piperazine-1-carboxamide Chemical compound O1C(CC)CN=C1C(C=C1Cl)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 UACQSHPMVFGLEW-UHFFFAOYSA-N 0.000 claims description 3
• GMHMCXJIVCUHHK-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[3-chloro-5-(5-methyl-1,3-oxazol-2-yl)pyridin-2-yl]piperazine-1-carboxamide Chemical compound O1C(C)=CN=C1C(C=C1Cl)=CN=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 GMHMCXJIVCUHHK-UHFFFAOYSA-N 0.000 claims description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
• KBNWMZBWSPYZLF-UHFFFAOYSA-N propan-2-yl 5-cyano-2-methyl-6-[3-[[4-(trifluoromethyl)phenyl]sulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=CC(=CC=2)C(F)(F)F)C1 KBNWMZBWSPYZLF-UHFFFAOYSA-N 0.000 claims description 3
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 2
• VCMOVXCUSZCATA-UHFFFAOYSA-N 1-[1-[3-cyano-5-(5-ethyl-1,3-oxazol-2-yl)-6-methylpyridin-2-yl]azetidin-3-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound O1C(CC)=CN=C1C1=CC(C#N)=C(N2CC(C2)NC(=O)NS(=O)(=O)C=2C=CC(C)=CC=2)N=C1C VCMOVXCUSZCATA-UHFFFAOYSA-N 0.000 claims description 2
• CVEAGYHCXXSRGU-UHFFFAOYSA-N 1-[3-amino-5-(5-ethyl-1,3-oxazol-2-yl)pyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylpiperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C(C=C1N)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 CVEAGYHCXXSRGU-UHFFFAOYSA-N 0.000 claims description 2
• XBPNTKUWKGRTFW-UHFFFAOYSA-N 1-[3-chloro-5-(5-ethyl-1,3-oxazol-2-yl)-4-methoxypyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylpiperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C(C(=C1Cl)OC)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 XBPNTKUWKGRTFW-UHFFFAOYSA-N 0.000 claims description 2
• OTNVITBUUXZTQF-UHFFFAOYSA-N 1-[3-chloro-5-(5-ethyl-1,3-oxazol-2-yl)-6-methoxypyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylpiperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C1=CC(Cl)=C(N2CCC(CC2)C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)N=C1OC OTNVITBUUXZTQF-UHFFFAOYSA-N 0.000 claims description 2
• LLNLUPUKRRVHGT-UHFFFAOYSA-N 1-[3-chloro-5-(5-ethyl-1,3-oxazol-2-yl)pyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylazetidine-3-carboxamide Chemical compound O1C(CC)=CN=C1C(C=C1Cl)=CN=C1N1CC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)C1 LLNLUPUKRRVHGT-UHFFFAOYSA-N 0.000 claims description 2
• QKKYTKNIBWEUKG-UHFFFAOYSA-N 1-[3-chloro-5-(5-ethyl-1,3-oxazol-2-yl)pyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylpiperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C(C=C1Cl)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 QKKYTKNIBWEUKG-UHFFFAOYSA-N 0.000 claims description 2
• QEZAVXUBUOSDEI-UHFFFAOYSA-N 1-[3-chloro-5-(5-propyl-1,3-oxazol-2-yl)pyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylpiperidine-4-carboxamide Chemical compound O1C(CCC)=CN=C1C(C=C1Cl)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 QEZAVXUBUOSDEI-UHFFFAOYSA-N 0.000 claims description 2
• JOFCRTUJZSGZJB-UHFFFAOYSA-N 1-[5-(5-butyl-1,3-oxazol-2-yl)-3-chloropyridin-2-yl]-n-(5-chlorothiophen-2-yl)sulfonylpiperidine-4-carboxamide Chemical compound O1C(CCCC)=CN=C1C(C=C1Cl)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 JOFCRTUJZSGZJB-UHFFFAOYSA-N 0.000 claims description 2
• INYUXDNBIIOJJT-UHFFFAOYSA-N 2,2-dimethylpropyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OCC(C)(C)C)C(C)=NC(N2CCC(CC2)C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)=C1C#N INYUXDNBIIOJJT-UHFFFAOYSA-N 0.000 claims description 2
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
• KTFDYVNEGTXQCV-UHFFFAOYSA-N 2-Thiophenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CS1 KTFDYVNEGTXQCV-UHFFFAOYSA-N 0.000 claims description 2
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
• DVMNZAAUBXQFFJ-UHFFFAOYSA-N ethyl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]-2,4-dimethylpyridine-3-carboxylate Chemical compound ClC1=C(C)C(C(=O)OCC)=C(C)N=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 DVMNZAAUBXQFFJ-UHFFFAOYSA-N 0.000 claims description 2
• HDTSQPHQWYPJHN-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[[5-(1,2-oxazol-3-yl)thiophen-2-yl]sulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2SC(=CC=2)C2=NOC=C2)C1 HDTSQPHQWYPJHN-UHFFFAOYSA-N 0.000 claims description 2
• TUEKMSMEFFRCRK-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[[5-(1,2-oxazol-5-yl)thiophen-2-yl]sulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2SC(=CC=2)C=2ON=CC=2)C1 TUEKMSMEFFRCRK-UHFFFAOYSA-N 0.000 claims description 2
• MUBTYELGPLBCFH-UHFFFAOYSA-N ethyl 5-cyano-6-[3-(2,3-dihydro-1-benzofuran-5-ylsulfonylcarbamoyl)azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C3CCOC3=CC=2)C1 MUBTYELGPLBCFH-UHFFFAOYSA-N 0.000 claims description 2
• CMHTWGGAVQSKAL-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,4-dimethyl-1,3-thiazol-5-yl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C2=C(N=C(C)S2)C)C1 CMHTWGGAVQSKAL-UHFFFAOYSA-N 0.000 claims description 2
• BGXQTUVWYLQULN-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,5-dichlorothiophen-3-yl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C2=C(SC(Cl)=C2)Cl)C1 BGXQTUVWYLQULN-UHFFFAOYSA-N 0.000 claims description 2
• WOSXZOGZKZBVKT-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2-fluorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)F)C1 WOSXZOGZKZBVKT-UHFFFAOYSA-N 0.000 claims description 2
• YUHYWCSQMSABOS-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3,4-dichlorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(Cl)C(Cl)=CC=2)C1 YUHYWCSQMSABOS-UHFFFAOYSA-N 0.000 claims description 2
• MHPMVBQMVHYRKR-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3,4-dimethoxyphenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(OC)C(OC)=CC=2)C1 MHPMVBQMVHYRKR-UHFFFAOYSA-N 0.000 claims description 2
• SYBXYCVFCLIGRZ-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3,5-difluorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(F)C=C(F)C=2)C1 SYBXYCVFCLIGRZ-UHFFFAOYSA-N 0.000 claims description 2
• DVYAJWIFDCCWGA-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3-cyanophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(C=CC=2)C#N)C1 DVYAJWIFDCCWGA-UHFFFAOYSA-N 0.000 claims description 2
• YFYRPFWOJLHUNU-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3-fluorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(F)C=CC=2)C1 YFYRPFWOJLHUNU-UHFFFAOYSA-N 0.000 claims description 2
• LNKAIDPJTVDPDQ-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3-methoxyphenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(OC)C=CC=2)C1 LNKAIDPJTVDPDQ-UHFFFAOYSA-N 0.000 claims description 2
• JYYCHOJJACQKFL-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4,5-dichlorothiophen-2-yl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2SC(Cl)=C(Cl)C=2)C1 JYYCHOJJACQKFL-UHFFFAOYSA-N 0.000 claims description 2
• VOVYHXLIGTYROG-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-cyanophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=CC(=CC=2)C#N)C1 VOVYHXLIGTYROG-UHFFFAOYSA-N 0.000 claims description 2
• JATGFNWHQMGBMT-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-fluorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=CC(F)=CC=2)C1 JATGFNWHQMGBMT-UHFFFAOYSA-N 0.000 claims description 2
• KVPUDJVNYHWGRL-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-methoxycarbonyl-5-methylfuran-2-yl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2OC(C)=C(C(=O)OC)C=2)C1 KVPUDJVNYHWGRL-UHFFFAOYSA-N 0.000 claims description 2
• TYMAWUNFRZHRGA-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(5-methoxycarbonylfuran-2-yl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2OC(=CC=2)C(=O)OC)C1 TYMAWUNFRZHRGA-UHFFFAOYSA-N 0.000 claims description 2
• NJFDXLVTTSQPFC-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(6-ethoxy-1,3-benzothiazol-2-yl)sulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2SC3=CC(OCC)=CC=C3N=2)C1 NJFDXLVTTSQPFC-UHFFFAOYSA-N 0.000 claims description 2
• KIPUPHQPSGWIFX-UHFFFAOYSA-N ethyl 5-cyano-6-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonylcarbamoyl)piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=C3OCCOC3=CC=2)CC1 KIPUPHQPSGWIFX-UHFFFAOYSA-N 0.000 claims description 2
• HTZUPOGLTWFCFA-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(2,4-dichlorophenyl)sulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C(=CC(Cl)=CC=2)Cl)CC1 HTZUPOGLTWFCFA-UHFFFAOYSA-N 0.000 claims description 2
• YNURQPMKLAELQO-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(3-cyanophenyl)sulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=C(C=CC=2)C#N)CC1 YNURQPMKLAELQO-UHFFFAOYSA-N 0.000 claims description 2
• PZRCOTDQTBAWDO-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-methoxyphenyl)sulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=CC(OC)=CC=2)CC1 PZRCOTDQTBAWDO-UHFFFAOYSA-N 0.000 claims description 2
• AINYGOJLEKAPSB-UHFFFAOYSA-N ethyl 6-[3-(1-benzothiophen-3-ylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C3=CC=CC=C3SC=2)C1 AINYGOJLEKAPSB-UHFFFAOYSA-N 0.000 claims description 2
• WJILKOXJPCLHAH-UHFFFAOYSA-N ethyl 6-[3-(2,1,3-benzothiadiazol-4-ylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C3=NSN=C3C=CC=2)C1 WJILKOXJPCLHAH-UHFFFAOYSA-N 0.000 claims description 2
• RSGPBIDJRJPCAV-UHFFFAOYSA-N ethyl 6-[3-(2,1,3-benzoxadiazol-4-ylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C3=NON=C3C=CC=2)C1 RSGPBIDJRJPCAV-UHFFFAOYSA-N 0.000 claims description 2
• LROWHZKBLPBFIX-UHFFFAOYSA-N ethyl 6-[3-(benzenesulfonylcarbamoylamino)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(NC(=O)NS(=O)(=O)C=2C=CC=CC=2)C1 LROWHZKBLPBFIX-UHFFFAOYSA-N 0.000 claims description 2
• QMUBZDPIKPJIAM-UHFFFAOYSA-N ethyl 6-[3-[(2-chlorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)Cl)C1 QMUBZDPIKPJIAM-UHFFFAOYSA-N 0.000 claims description 2
• XJAUTURGAVKIGW-UHFFFAOYSA-N ethyl 6-[3-[(4-chlorophenyl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)C1 XJAUTURGAVKIGW-UHFFFAOYSA-N 0.000 claims description 2
• MFBHEUSXFARQEY-UHFFFAOYSA-N ethyl 6-[3-[(5-chloro-1,3-dimethylpyrazol-4-yl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C2=C(N(C)N=C2C)Cl)C1 MFBHEUSXFARQEY-UHFFFAOYSA-N 0.000 claims description 2
• NLKBKVGXCVMBPS-UHFFFAOYSA-N ethyl 6-[3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C2=C(C3=CC(Cl)=CC=C3S2)C)C1 NLKBKVGXCVMBPS-UHFFFAOYSA-N 0.000 claims description 2
• IQELNXOCRWDSJQ-UHFFFAOYSA-N ethyl 6-[3-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-3-methylazetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C)(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)C1 IQELNXOCRWDSJQ-UHFFFAOYSA-N 0.000 claims description 2
• WSZQGNXHCKRDDX-UHFFFAOYSA-N ethyl 6-[3-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2N3C=CSC3=NC=2Cl)C1 WSZQGNXHCKRDDX-UHFFFAOYSA-N 0.000 claims description 2
• GPRURVBIOGGQIW-UHFFFAOYSA-N ethyl 6-[3-[(benzenesulfonylcarbamoylamino)methyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(CNC(=O)NS(=O)(=O)C=2C=CC=CC=2)C1 GPRURVBIOGGQIW-UHFFFAOYSA-N 0.000 claims description 2
• BTIAERCPSGMCCD-UHFFFAOYSA-N ethyl 6-[3-[2-(benzenesulfonamido)-2-oxoethyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(CC(=O)NS(=O)(=O)C=2C=CC=CC=2)CCC1 BTIAERCPSGMCCD-UHFFFAOYSA-N 0.000 claims description 2
• OLFOOGHYEKTXRY-UHFFFAOYSA-N ethyl 6-[3-[[(5-chlorothiophen-2-yl)sulfonylcarbamoylamino]methyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(CNC(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)C1 OLFOOGHYEKTXRY-UHFFFAOYSA-N 0.000 claims description 2
• FWXUMSNWEZCCIT-UHFFFAOYSA-N ethyl 6-[3-[[4-(4-chlorophenyl)sulfonyl-3-methylthiophen-2-yl]sulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C2=C(C(=CS2)S(=O)(=O)C=2C=CC(Cl)=CC=2)C)C1 FWXUMSNWEZCCIT-UHFFFAOYSA-N 0.000 claims description 2
• MSQMWODDPRBPJG-UHFFFAOYSA-N ethyl 6-[4-(2,1,3-benzoxadiazol-4-ylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C3=NON=C3C=CC=2)CC1 MSQMWODDPRBPJG-UHFFFAOYSA-N 0.000 claims description 2
• SLFSAOTXKZLYMH-UHFFFAOYSA-N ethyl 6-[4-(benzenesulfonylcarbamoyl)-1,4-diazepan-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CCC1 SLFSAOTXKZLYMH-UHFFFAOYSA-N 0.000 claims description 2
• KVFVNZJNEHTWDB-UHFFFAOYSA-N ethyl 6-[4-[(4-chlorophenyl)sulfonylcarbamoylamino]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(NC(=O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)CC1 KVFVNZJNEHTWDB-UHFFFAOYSA-N 0.000 claims description 2
• WXFHJUTYLPESPH-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]-1,4-diazepan-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCN(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CCC1 WXFHJUTYLPESPH-UHFFFAOYSA-N 0.000 claims description 2
• CMEULPCPRSODMC-UHFFFAOYSA-N ethyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]-2,4-dimethylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=C(C)C=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 CMEULPCPRSODMC-UHFFFAOYSA-N 0.000 claims description 2
• NWSAQANIQYQTHL-UHFFFAOYSA-N ethyl 6-[4-[2-(benzenesulfonamido)-2-oxoethyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(CC(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 NWSAQANIQYQTHL-UHFFFAOYSA-N 0.000 claims description 2
• ORDYIRKFBRMZAQ-UHFFFAOYSA-N ethyl 6-[4-[2-[(5-chlorothiophen-2-yl)sulfonylamino]-2-oxoethyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(CC(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 ORDYIRKFBRMZAQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
• SVYOVAPCHNLQFI-UHFFFAOYSA-N n-(5-chlorothiophen-2-yl)sulfonyl-1-[5-(5-ethyl-1,3-oxazol-2-yl)-3-methylpyridin-2-yl]piperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C(C=C1C)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 SVYOVAPCHNLQFI-UHFFFAOYSA-N 0.000 claims description 2
• QXWFPNSWNSIFHP-UHFFFAOYSA-N n-(5-chlorothiophen-2-yl)sulfonyl-1-[5-(5-ethyl-1,3-oxazol-2-yl)-3-nitropyridin-2-yl]piperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C(C=C1[N+]([O-])=O)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 QXWFPNSWNSIFHP-UHFFFAOYSA-N 0.000 claims description 2
• 125000006252 n-propylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 claims description 2
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 2
• FENUGUXRROVJPM-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[4-[(4-methoxyphenyl)sulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)NC(=O)C1CCN(C=2C(=CC(=C(C)N=2)C(=O)OC(C)C)C#N)CC1 FENUGUXRROVJPM-UHFFFAOYSA-N 0.000 claims description 2
• NAVRLPPYEYKSHS-UHFFFAOYSA-N propan-2-yl 6-[3-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]azetidin-1-yl]-5-ethynyl-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#C)=C1N1CC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)C1 NAVRLPPYEYKSHS-UHFFFAOYSA-N 0.000 claims description 2
• XTDMWHYNGVIWJB-UHFFFAOYSA-N propan-2-yl 6-[4-(benzenesulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)CC1 XTDMWHYNGVIWJB-UHFFFAOYSA-N 0.000 claims description 2
• ZHPWBXDMTDFJAT-UHFFFAOYSA-N propan-2-yl 6-[4-[(3-bromophenyl)sulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=C(Br)C=CC=2)CC1 ZHPWBXDMTDFJAT-UHFFFAOYSA-N 0.000 claims description 2
• LCEALTZDXMMLFT-UHFFFAOYSA-N propan-2-yl 6-[4-[(4-chlorophenyl)sulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)CC1 LCEALTZDXMMLFT-UHFFFAOYSA-N 0.000 claims description 2
• UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 claims description 2
• RUFQLCKFXFDRFY-UHFFFAOYSA-N tert-butyl 5-chloro-6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OC(C)(C)C)=CN=C1N1CCC(C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 RUFQLCKFXFDRFY-UHFFFAOYSA-N 0.000 claims description 2
• JTNZXLLKKARAHG-UHFFFAOYSA-N tert-butyl 6-[4-[(5-chlorothiophen-2-yl)sulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OC(C)(C)C)C(C)=NC(N2CCC(CC2)C(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)=C1C#N JTNZXLLKKARAHG-UHFFFAOYSA-N 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 12
• VALZSZJVEFACEZ-UHFFFAOYSA-N azetidine-3-carboxamide Chemical compound NC(=O)C1CNC1 VALZSZJVEFACEZ-UHFFFAOYSA-N 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 15
• 239000003146 anticoagulant agent Substances 0.000 abstract description 5
• 150000003222 pyridines Chemical class 0.000 abstract description 3
• 229960004676 antithrombotic agent Drugs 0.000 abstract description 2
• 208000024172 Cardiovascular disease Diseases 0.000 abstract 1
• 239000002172 P2Y12 inhibitor Substances 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 234
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 188
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 132
• 239000011541 reaction mixture Substances 0.000 description 118
• 235000019439 ethyl acetate Nutrition 0.000 description 111
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 110
• 230000002829 reductive effect Effects 0.000 description 99
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 98
• 239000000460 chlorine Substances 0.000 description 88
• 238000006243 chemical reaction Methods 0.000 description 81
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 76
• 238000005481 NMR spectroscopy Methods 0.000 description 72
• 239000002904 solvent Substances 0.000 description 54
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• 238000003818 flash chromatography Methods 0.000 description 49
• 239000012043 crude product Substances 0.000 description 42
• 229920006395 saturated elastomer Polymers 0.000 description 40
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• 239000007787 solid Substances 0.000 description 39
• 210000001772 blood platelet Anatomy 0.000 description 37
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 35
• 239000000203 mixture Substances 0.000 description 34
• 239000000243 solution Substances 0.000 description 30
• 239000012267 brine Substances 0.000 description 27
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 24
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
• 229940086542 triethylamine Drugs 0.000 description 22
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
• 150000007530 organic bases Chemical class 0.000 description 21
• 238000002953 preparative HPLC Methods 0.000 description 21
• 239000000872 buffer Substances 0.000 description 19
• 239000003153 chemical reaction reagent Substances 0.000 description 19
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 18
• 238000000746 purification Methods 0.000 description 18
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 16
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 239000001257 hydrogen Substances 0.000 description 15
• 230000008569 process Effects 0.000 description 15
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 14
• 239000005695 Ammonium acetate Substances 0.000 description 14
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