KR20080039405A - 신규한 피리딘 유사체 - Google Patents
신규한 피리딘 유사체 Download PDFInfo
- Publication number
- KR20080039405A KR20080039405A KR1020087002914A KR20087002914A KR20080039405A KR 20080039405 A KR20080039405 A KR 20080039405A KR 1020087002914 A KR1020087002914 A KR 1020087002914A KR 20087002914 A KR20087002914 A KR 20087002914A KR 20080039405 A KR20080039405 A KR 20080039405A
- Authority
- KR
- South Korea
- Prior art keywords
- cyano
- amino
- aryl
- heterocyclyl
- alkyl
- Prior art date
- 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- Withdrawn
Links
- 150000003222 pyridines Chemical class 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 252
- 238000000034 method Methods 0.000 claims abstract description 103
- 239000003814 drug Substances 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- -1 arylC (O) Chemical group 0.000 claims description 274
- 125000003118 aryl group Chemical group 0.000 claims description 265
- 125000000623 heterocyclic group Chemical group 0.000 claims description 264
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 168
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 164
- 239000000460 chlorine Substances 0.000 claims description 158
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 140
- 229910052736 halogen Inorganic materials 0.000 claims description 140
- 229910052801 chlorine Inorganic materials 0.000 claims description 136
- 229910052794 bromium Inorganic materials 0.000 claims description 133
- 229910052731 fluorine Inorganic materials 0.000 claims description 133
- 229910052740 iodine Inorganic materials 0.000 claims description 133
- 150000002367 halogens Chemical class 0.000 claims description 129
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 120
- 239000011541 reaction mixture Substances 0.000 claims description 118
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 112
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 104
- 125000004429 atom Chemical group 0.000 claims description 103
- 229910052757 nitrogen Inorganic materials 0.000 claims description 102
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 101
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 90
- 229910052760 oxygen Inorganic materials 0.000 claims description 88
- 239000001301 oxygen Substances 0.000 claims description 88
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 86
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 81
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 76
- 125000004414 alkyl thio group Chemical group 0.000 claims description 75
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 72
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 65
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 58
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 56
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 55
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 55
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 48
- 230000008569 process Effects 0.000 claims description 48
- 125000004122 cyclic group Chemical group 0.000 claims description 42
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 41
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 38
- 125000002947 alkylene group Chemical group 0.000 claims description 35
- 125000005110 aryl thio group Chemical group 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 32
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 32
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 32
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 32
- 125000005843 halogen group Chemical group 0.000 claims description 30
- 150000007530 organic bases Chemical class 0.000 claims description 27
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 25
- 239000012442 inert solvent Substances 0.000 claims description 25
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 17
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 16
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000000217 alkyl group Chemical group 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
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 14
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 10
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 10
- 239000012317 TBTU Substances 0.000 claims description 10
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 claims description 10
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 10
- 229960001238 methylnicotinate Drugs 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 239000003960 organic solvent Substances 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
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 8
- 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 8
- 235000001968 nicotinic acid Nutrition 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 7
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- NEMHKCNXXRQYRF-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)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)CC=2C=CC=CC=2)CC1 NEMHKCNXXRQYRF-UHFFFAOYSA-N 0.000 claims description 6
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000005238 alkylenediamino group Chemical group 0.000 claims description 5
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000007822 coupling agent Substances 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- RTNNCTNNKKJRPJ-UHFFFAOYSA-N 2,2-dimethylpropyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OCC(C)(C)C)C(C)=NC(N2CC(C2)C(=O)NS(=O)(=O)CC=2C=CC=CC=2)=C1C#N RTNNCTNNKKJRPJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 239000012320 chlorinating reagent Substances 0.000 claims description 4
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- CBNBJDRCUVOVHQ-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-cyanophenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(=CC=2)C#N)CC1 CBNBJDRCUVOVHQ-UHFFFAOYSA-N 0.000 claims description 4
- LJFYTTRWLIZFAV-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)-4-methylpiperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C)(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 LJFYTTRWLIZFAV-UHFFFAOYSA-N 0.000 claims description 4
- IXBMBIDEPNYMBM-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)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)CC=2C=CC=CC=2)CC1 IXBMBIDEPNYMBM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 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
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- ULVLKRBRUKKOCE-UHFFFAOYSA-N cyclopentyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N#CC=1C=C(C(=O)OC2CCCC2)C(C)=NC=1N(C1)CC1C(=O)NS(=O)(=O)CC1=CC=CC=C1 ULVLKRBRUKKOCE-UHFFFAOYSA-N 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 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
- WSFQBRDMYJEGQC-UHFFFAOYSA-N ethyl 4-amino-6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-chloropyridine-3-carboxylate Chemical compound ClC1=C(N)C(C(=O)OCC)=CN=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 WSFQBRDMYJEGQC-UHFFFAOYSA-N 0.000 claims description 3
- MHVCUXIPQLILBY-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[2-(2-fluorophenyl)ethylsulfonylcarbamoyl]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)CCC=2C(=CC=CC=2)F)C1 MHVCUXIPQLILBY-UHFFFAOYSA-N 0.000 claims description 3
- AOOWVFPXPVQQGP-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoyl)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)CC=2C=CC=CC=2)C1 AOOWVFPXPVQQGP-UHFFFAOYSA-N 0.000 claims description 3
- WWDNTQYRTZSERA-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoylamino)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)CC=2C=CC=CC=2)C1 WWDNTQYRTZSERA-UHFFFAOYSA-N 0.000 claims description 3
- MHLSMSJZGMWZDH-UHFFFAOYSA-N ethyl 6-[3-[2-(benzylsulfonylamino)-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)CC=2C=CC=CC=2)CCC1 MHLSMSJZGMWZDH-UHFFFAOYSA-N 0.000 claims description 3
- OBOPZXVABNAFRJ-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)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)CC=2C=CC=CC=2)CC1 OBOPZXVABNAFRJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 3
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
- HLCHHYWSCZAXFP-UHFFFAOYSA-N propan-2-yl 6-[4-(benzylsulfonylcarbamoyl)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)CC=2C=CC=CC=2)CC1 HLCHHYWSCZAXFP-UHFFFAOYSA-N 0.000 claims description 3
- TXDUMJCBSYDACJ-UHFFFAOYSA-N propyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 TXDUMJCBSYDACJ-UHFFFAOYSA-N 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- LKMOJJVOGNLJLL-UHFFFAOYSA-N tert-butyl 6-[3-(benzylsulfonylcarbamoylamino)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OC(C)(C)C)C(C)=NC(N2CC(C2)NC(=O)NS(=O)(=O)CC=2C=CC=CC=2)=C1C#N LKMOJJVOGNLJLL-UHFFFAOYSA-N 0.000 claims description 3
- DSMIBOGQTGQEDW-UHFFFAOYSA-N (4-fluorophenyl)methyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N#CC=1C=C(C(=O)OCC=2C=CC(F)=CC=2)C(C)=NC=1N(CC1)CCC1C(=O)NS(=O)(=O)CC1=CC=CC=C1 DSMIBOGQTGQEDW-UHFFFAOYSA-N 0.000 claims description 2
- WLXBIIXQTWAAQL-UHFFFAOYSA-N 2,2,2-trifluoroethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OCC(F)(F)F)C(C)=NC(N2CC(C2)C(=O)NS(=O)(=O)CC=2C=CC=CC=2)=C1C#N WLXBIIXQTWAAQL-UHFFFAOYSA-N 0.000 claims description 2
- QJJDJLLSRVUGIJ-UHFFFAOYSA-N 2,2,2-trifluoroethyl 6-[3-[(4-chlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OCC(F)(F)F)C(C)=NC(N2CC(C2)C(=O)NS(=O)(=O)CC=2C=CC(Cl)=CC=2)=C1C#N QJJDJLLSRVUGIJ-UHFFFAOYSA-N 0.000 claims description 2
- GNRNQOQWCLJMFS-UHFFFAOYSA-N 2,2,2-trifluoroethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OCC(F)(F)F)C(C)=NC(N2CCC(CC2)C(=O)NS(=O)(=O)CC=2C=CC=CC=2)=C1C#N GNRNQOQWCLJMFS-UHFFFAOYSA-N 0.000 claims description 2
- BZNVZLHHMIUXDP-UHFFFAOYSA-N 2,2-dimethylpropyl 6-[4-(benzylsulfonylcarbamoyl)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)CC=2C=CC=CC=2)=C1C#N BZNVZLHHMIUXDP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 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
- ZXVQGNIVTPFDQM-UHFFFAOYSA-N 2-hydroxyethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound C1=C(C(=O)OCCO)C(C)=NC(N2CC(C2)C(=O)NS(=O)(=O)CC=2C=CC=CC=2)=C1C#N ZXVQGNIVTPFDQM-UHFFFAOYSA-N 0.000 claims description 2
- VPLBKEKVVMABJJ-UHFFFAOYSA-N 2-methylpropyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC(C)C)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 VPLBKEKVVMABJJ-UHFFFAOYSA-N 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
- 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
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 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
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 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
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical group CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 2
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
- ZJWIYTDVQVMBDZ-UHFFFAOYSA-N benzyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N#CC=1C=C(C(=O)OCC=2C=CC=CC=2)C(C)=NC=1N(C1)CC1C(=O)NS(=O)(=O)CC1=CC=CC=C1 ZJWIYTDVQVMBDZ-UHFFFAOYSA-N 0.000 claims description 2
- PBOQDJVWNSTWCJ-UHFFFAOYSA-N benzyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N#CC=1C=C(C(=O)OCC=2C=CC=CC=2)C(C)=NC=1N(CC1)CCC1C(=O)NS(=O)(=O)CC1=CC=CC=C1 PBOQDJVWNSTWCJ-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 2
- UMTRKVMYQFZJMO-UHFFFAOYSA-N cyclobutyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N#CC=1C=C(C(=O)OC2CCC2)C(C)=NC=1N(C1)CC1C(=O)NS(=O)(=O)CC1=CC=CC=C1 UMTRKVMYQFZJMO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- LUHXCFFTYVLFQM-UHFFFAOYSA-N cyclopropyl 5-cyano-2-methyl-6-[4-[(4-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(C)=CC=C1CS(=O)(=O)NC(=O)C1CCN(C=2C(=CC(=C(C)N=2)C(=O)OC2CC2)C#N)CC1 LUHXCFFTYVLFQM-UHFFFAOYSA-N 0.000 claims description 2
- FJCSFEJMLKZLMT-UHFFFAOYSA-N cyclopropyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N#CC=1C=C(C(=O)OC2CC2)C(C)=NC=1N(C1)CC1C(=O)NS(=O)(=O)CC1=CC=CC=C1 FJCSFEJMLKZLMT-UHFFFAOYSA-N 0.000 claims description 2
- KNVDTAVEWDSSEK-UHFFFAOYSA-N cyclopropyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N#CC=1C=C(C(=O)OC2CC2)C(C)=NC=1N(CC1)CCC1C(=O)NS(=O)(=O)CC1=CC=CC=C1 KNVDTAVEWDSSEK-UHFFFAOYSA-N 0.000 claims description 2
- HQOVDLZFJOBAPA-UHFFFAOYSA-N ethyl 4-amino-6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-chloropyridine-3-carboxylate Chemical compound ClC1=C(N)C(C(=O)OCC)=CN=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 HQOVDLZFJOBAPA-UHFFFAOYSA-N 0.000 claims description 2
- SRRYCJVTVMZIHX-UHFFFAOYSA-N ethyl 5-acetyl-6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C(C)=O)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 SRRYCJVTVMZIHX-UHFFFAOYSA-N 0.000 claims description 2
- UXYBLEGVEGVEKZ-UHFFFAOYSA-N ethyl 5-chloro-2-methyl-6-[3-[(4-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(Cl)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)C1 UXYBLEGVEGVEKZ-UHFFFAOYSA-N 0.000 claims description 2
- QIPGXRUPKYFZGX-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-(1-phenylethylsulfonylcarbamoyl)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(C)C=2C=CC=CC=2)C1 QIPGXRUPKYFZGX-UHFFFAOYSA-N 0.000 claims description 2
- TXYSLOQUANFYQS-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-(2-phenylethylsulfonylcarbamoyl)azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CCC=2C=CC=CC=2)C1 TXYSLOQUANFYQS-UHFFFAOYSA-N 0.000 claims description 2
- GGTGWEIXAJXKKN-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[(2-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)C)C1 GGTGWEIXAJXKKN-UHFFFAOYSA-N 0.000 claims description 2
- OYDVLTHFEYJJPT-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[(3-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)C1 OYDVLTHFEYJJPT-UHFFFAOYSA-N 0.000 claims description 2
- AHPLEFBSLFSXQR-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[(3-nitrophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(C=CC=2)[N+]([O-])=O)C1 AHPLEFBSLFSXQR-UHFFFAOYSA-N 0.000 claims description 2
- FIXSKMNOWATHBV-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[(4-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)C1 FIXSKMNOWATHBV-UHFFFAOYSA-N 0.000 claims description 2
- QEWJFGLCRRYNHH-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[(4-nitrophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(=CC=2)[N+]([O-])=O)C1 QEWJFGLCRRYNHH-UHFFFAOYSA-N 0.000 claims description 2
- UKHUKUHMXHHHJJ-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[(4-propan-2-ylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(=CC=2)C(C)C)C1 UKHUKUHMXHHHJJ-UHFFFAOYSA-N 0.000 claims description 2
- NTXGBBFZHIKABO-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[[2-(trifluoromethyl)phenyl]methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)C(F)(F)F)C1 NTXGBBFZHIKABO-UHFFFAOYSA-N 0.000 claims description 2
- YEBSUQZFWGNSHC-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[[3-(trifluoromethyl)phenyl]methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(C=CC=2)C(F)(F)F)C1 YEBSUQZFWGNSHC-UHFFFAOYSA-N 0.000 claims description 2
- VPLUUYJJYUEQQB-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[[4-(trifluoromethyl)phenyl]methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(=CC=2)C(F)(F)F)C1 VPLUUYJJYUEQQB-UHFFFAOYSA-N 0.000 claims description 2
- PDPLLSUKTDXTRW-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[4-(phenylsulfamoylcarbamoyl)piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)NC=2C=CC=CC=2)CC1 PDPLLSUKTDXTRW-UHFFFAOYSA-N 0.000 claims description 2
- RZYSBVBLRUQPMI-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[4-[(3-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)CC1 RZYSBVBLRUQPMI-UHFFFAOYSA-N 0.000 claims description 2
- XSAIJRMURHASGT-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[4-[(4-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)CC1 XSAIJRMURHASGT-UHFFFAOYSA-N 0.000 claims description 2
- MRWKTKIMIMOEBX-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[4-[(4-propan-2-ylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(=CC=2)C(C)C)CC1 MRWKTKIMIMOEBX-UHFFFAOYSA-N 0.000 claims description 2
- AXOZUWQJVWCETH-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[4-[[methyl(phenyl)sulfamoyl]carbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)N(C)C=2C=CC=CC=2)CC1 AXOZUWQJVWCETH-UHFFFAOYSA-N 0.000 claims description 2
- WGFQRYABVMIEHB-UHFFFAOYSA-N ethyl 5-cyano-6-[3-(cyclohexylmethylsulfonylcarbamoyl)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)CC2CCCCC2)C1 WGFQRYABVMIEHB-UHFFFAOYSA-N 0.000 claims description 2
- NWTXBNNLXZXHMB-UHFFFAOYSA-N ethyl 5-cyano-6-[3-(cyclopentylmethylsulfonylcarbamoyl)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)CC2CCCC2)C1 NWTXBNNLXZXHMB-UHFFFAOYSA-N 0.000 claims description 2
- NEMKBRBSVCERQQ-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,5-dimethylphenyl)methylsulfonylcarbamoyl]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)CC=2C(=CC=C(C)C=2)C)C1 NEMKBRBSVCERQQ-UHFFFAOYSA-N 0.000 claims description 2
- IMJUSMMVQCRREF-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2-methoxycarbonylphenyl)methylsulfonylcarbamoyl]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)CC=2C(=CC=CC=2)C(=O)OC)C1 IMJUSMMVQCRREF-UHFFFAOYSA-N 0.000 claims description 2
- COEWLICRHDDJDL-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3,4-dichlorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(Cl)C(Cl)=CC=2)C1 COEWLICRHDDJDL-UHFFFAOYSA-N 0.000 claims description 2
- GEUWGPOYJULDMW-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3,5-dichlorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(Cl)C=C(Cl)C=2)C1 GEUWGPOYJULDMW-UHFFFAOYSA-N 0.000 claims description 2
- WMYHSMIYXPQWFN-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3,5-dimethylphenyl)methylsulfonylcarbamoyl]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)CC=2C=C(C)C=C(C)C=2)C1 WMYHSMIYXPQWFN-UHFFFAOYSA-N 0.000 claims description 2
- APRNRDHUNOUQBH-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3-fluorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(F)C=CC=2)C1 APRNRDHUNOUQBH-UHFFFAOYSA-N 0.000 claims description 2
- VAKWRLPIOIKQHX-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-cyanophenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(=CC=2)C#N)C1 VAKWRLPIOIKQHX-UHFFFAOYSA-N 0.000 claims description 2
- GKUTXOAQZPNFCB-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-fluorophenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(F)=CC=2)C1 GKUTXOAQZPNFCB-UHFFFAOYSA-N 0.000 claims description 2
- HGAVMTCXGNYXAQ-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-methoxyphenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(OC)=CC=2)C1 HGAVMTCXGNYXAQ-UHFFFAOYSA-N 0.000 claims description 2
- ZQKOJZJZZZIJES-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[2-(3-fluorophenyl)ethylsulfonylcarbamoyl]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)CCC=2C=C(F)C=CC=2)C1 ZQKOJZJZZZIJES-UHFFFAOYSA-N 0.000 claims description 2
- CRMGZAQUXRSVMC-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[2-(4-fluorophenyl)ethylsulfonylcarbamoyl]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)CCC=2C=CC(F)=CC=2)C1 CRMGZAQUXRSVMC-UHFFFAOYSA-N 0.000 claims description 2
- REZODNUYNHOHNL-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[2-[(4-fluorophenyl)methylsulfonylamino]-2-oxoethyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(CC(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)C1 REZODNUYNHOHNL-UHFFFAOYSA-N 0.000 claims description 2
- LVOWCCHYSGPJIN-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[3-(4-methoxyphenoxy)propylsulfonylcarbamoyl]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)CCCOC=2C=CC(OC)=CC=2)C1 LVOWCCHYSGPJIN-UHFFFAOYSA-N 0.000 claims description 2
- XYJPLPXCGUNDGC-UHFFFAOYSA-N ethyl 5-cyano-6-[4-(cyclopentylmethylsulfonylcarbamoyl)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)CC2CCCC2)CC1 XYJPLPXCGUNDGC-UHFFFAOYSA-N 0.000 claims description 2
- MBVSZRNGIDMXOW-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(2,5-dimethylphenyl)methylsulfonylcarbamoyl]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)CC=2C(=CC=C(C)C=2)C)CC1 MBVSZRNGIDMXOW-UHFFFAOYSA-N 0.000 claims description 2
- RZHRAGRVVVNEIY-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(2-methoxycarbonylphenyl)methylsulfonylcarbamoyl]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)CC=2C(=CC=CC=2)C(=O)OC)CC1 RZHRAGRVVVNEIY-UHFFFAOYSA-N 0.000 claims description 2
- QKSITYLIDWAICY-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(3,4-dichlorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(Cl)C(Cl)=CC=2)CC1 QKSITYLIDWAICY-UHFFFAOYSA-N 0.000 claims description 2
- XNKVSBVPFBVLLF-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(3,4-difluorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(F)C(F)=CC=2)CC1 XNKVSBVPFBVLLF-UHFFFAOYSA-N 0.000 claims description 2
- HDZJHDQIFRZTQI-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(3-fluoro-4-methylphenyl)methylsulfonylcarbamoyl]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)CC=2C=C(F)C(C)=CC=2)CC1 HDZJHDQIFRZTQI-UHFFFAOYSA-N 0.000 claims description 2
- CBSUFKGUQSMUKL-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(3-fluorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(F)C=CC=2)CC1 CBSUFKGUQSMUKL-UHFFFAOYSA-N 0.000 claims description 2
- SWNUIVYHXUKLOA-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-ethylphenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(CC)=CC=2)CC1 SWNUIVYHXUKLOA-UHFFFAOYSA-N 0.000 claims description 2
- QSJSWBPRIPCKFT-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-methoxyphenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(OC)=CC=2)CC1 QSJSWBPRIPCKFT-UHFFFAOYSA-N 0.000 claims description 2
- PIIPBUHRYZTOBN-UHFFFAOYSA-N ethyl 6-[3-(1,2-benzoxazol-3-ylmethylsulfonylcarbamoyl)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)CC=2C3=CC=CC=C3ON=2)C1 PIIPBUHRYZTOBN-UHFFFAOYSA-N 0.000 claims description 2
- OUVUTJDZUWKAFY-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-(4-methoxy-4-oxobutoxy)-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(OCCCC(=O)OC)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 OUVUTJDZUWKAFY-UHFFFAOYSA-N 0.000 claims description 2
- MJJANTQEMALEFE-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-chloro-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(Cl)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 MJJANTQEMALEFE-UHFFFAOYSA-N 0.000 claims description 2
- GVCOWNSYYVZKDI-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-ethylpyridine-3-carboxylate Chemical compound N1=C(CC)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 GVCOWNSYYVZKDI-UHFFFAOYSA-N 0.000 claims description 2
- XCSORGQATWEGRC-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-propan-2-ylpyridine-3-carboxylate Chemical compound N1=C(C(C)C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 XCSORGQATWEGRC-UHFFFAOYSA-N 0.000 claims description 2
- RBXZVMWNFVOQSK-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-methoxy-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(OC)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 RBXZVMWNFVOQSK-UHFFFAOYSA-N 0.000 claims description 2
- HTHLMJZCNFPPMO-UHFFFAOYSA-N ethyl 6-[3-[(2-chlorophenyl)methylsulfonylcarbamoyl]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)CC=2C(=CC=CC=2)Cl)C1 HTHLMJZCNFPPMO-UHFFFAOYSA-N 0.000 claims description 2
- KXINOQPORLBYGK-UHFFFAOYSA-N ethyl 6-[3-[(3-bromophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(Br)C=CC=2)C1 KXINOQPORLBYGK-UHFFFAOYSA-N 0.000 claims description 2
- OXCAXVZZNQBTKJ-UHFFFAOYSA-N ethyl 6-[3-[(3-chlorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(Cl)C=CC=2)C1 OXCAXVZZNQBTKJ-UHFFFAOYSA-N 0.000 claims description 2
- FZGNWTQJSVKAPD-UHFFFAOYSA-N ethyl 6-[3-[(4-chlorophenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(Cl)=CC=2)C1 FZGNWTQJSVKAPD-UHFFFAOYSA-N 0.000 claims description 2
- RCAVJWRLMXMMMY-UHFFFAOYSA-N ethyl 6-[3-[2-(3-chlorophenyl)ethylsulfonylcarbamoyl]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)CCC=2C=C(Cl)C=CC=2)C1 RCAVJWRLMXMMMY-UHFFFAOYSA-N 0.000 claims description 2
- NMPBGGNVVITFFE-UHFFFAOYSA-N ethyl 6-[3-[2-(benzylsulfonylamino)-2-oxoethyl]azetidin-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)CC=2C=CC=CC=2)C1 NMPBGGNVVITFFE-UHFFFAOYSA-N 0.000 claims description 2
- PZBGLWIOHXYBOZ-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)-4-[(2-methylpropan-2-yl)oxycarbonylamino]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)CC=2C=CC=CC=2)(NC(=O)OC(C)(C)C)CC1 PZBGLWIOHXYBOZ-UHFFFAOYSA-N 0.000 claims description 2
- QGFBBJWQEKQPQP-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-(4-methoxy-4-oxobutoxy)-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(OCCCC(=O)OC)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 QGFBBJWQEKQPQP-UHFFFAOYSA-N 0.000 claims description 2
- HTTBICQNSWIDFU-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-chloro-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(Cl)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 HTTBICQNSWIDFU-UHFFFAOYSA-N 0.000 claims description 2
- GSGKAPDDEQEGJK-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-(dimethylamino)pyridine-3-carboxylate Chemical compound N1=C(N(C)C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 GSGKAPDDEQEGJK-UHFFFAOYSA-N 0.000 claims description 2
- XBDVSNZJEZABEP-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoylamino)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)CC=2C=CC=CC=2)CC1 XBDVSNZJEZABEP-UHFFFAOYSA-N 0.000 claims description 2
- VCHQDCHZZVXQEH-UHFFFAOYSA-N ethyl 6-[4-[(4-chlorophenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(Cl)=CC=2)CC1 VCHQDCHZZVXQEH-UHFFFAOYSA-N 0.000 claims description 2
- ZOEWYDNFJGUSCM-UHFFFAOYSA-N ethyl 6-[4-amino-4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(N)(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 ZOEWYDNFJGUSCM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 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
- JSARWDFDTMLIQR-UHFFFAOYSA-N methyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 JSARWDFDTMLIQR-UHFFFAOYSA-N 0.000 claims description 2
- DAQKYANULOKBQC-UHFFFAOYSA-N n-(1,2-benzoxazol-3-ylmethylsulfonyl)-1-[3-cyano-5-(5-ethyl-1,3-oxazol-2-yl)-6-methylpyridin-2-yl]piperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C1=CC(C#N)=C(N2CCC(CC2)C(=O)NS(=O)(=O)CC=2C3=CC=CC=C3ON=2)N=C1C DAQKYANULOKBQC-UHFFFAOYSA-N 0.000 claims description 2
- LZYALNMJKMYPCI-UHFFFAOYSA-N n-benzylsulfonyl-1-[3-chloro-5-(5-ethyl-1,3-oxazol-2-yl)pyridin-2-yl]piperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C(C=C1Cl)=CN=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 LZYALNMJKMYPCI-UHFFFAOYSA-N 0.000 claims description 2
- ZJFUNJPZCMPXMF-UHFFFAOYSA-N n-benzylsulfonyl-1-[3-cyano-5-(5-ethyl-1,3-oxazol-2-yl)-6-methylpyridin-2-yl]piperidine-4-carboxamide Chemical compound O1C(CC)=CN=C1C1=CC(C#N)=C(N2CCC(CC2)C(=O)NS(=O)(=O)CC=2C=CC=CC=2)N=C1C ZJFUNJPZCMPXMF-UHFFFAOYSA-N 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
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 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
- GCTWCJFKPJBURF-UHFFFAOYSA-N propan-2-yl 5-cyano-2-methyl-6-[4-[(3-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)CC1 GCTWCJFKPJBURF-UHFFFAOYSA-N 0.000 claims description 2
- VDHCPQNFVJOLDK-UHFFFAOYSA-N propan-2-yl 5-cyano-2-methyl-6-[4-[(4-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)CC1 VDHCPQNFVJOLDK-UHFFFAOYSA-N 0.000 claims description 2
- PFLVQDGJTUUYES-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[3-(cyclopentylmethylsulfonylcarbamoyl)azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC2CCCC2)C1 PFLVQDGJTUUYES-UHFFFAOYSA-N 0.000 claims description 2
- ONVPUNPXKAMMNX-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[3-[(2-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)F)C1 ONVPUNPXKAMMNX-UHFFFAOYSA-N 0.000 claims description 2
- BYFFWHYMGIELAN-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[3-[(2-methoxycarbonylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CC=C1CS(=O)(=O)NC(=O)C1CN(C=2C(=CC(=C(C)N=2)C(=O)OC(C)C)C#N)C1 BYFFWHYMGIELAN-UHFFFAOYSA-N 0.000 claims description 2
- VQHRBYDEBVEROS-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[3-[(3-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(F)C=CC=2)C1 VQHRBYDEBVEROS-UHFFFAOYSA-N 0.000 claims description 2
- DBZFSXGSHLBVFC-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[3-[(4-cyanophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(=CC=2)C#N)C1 DBZFSXGSHLBVFC-UHFFFAOYSA-N 0.000 claims description 2
- INKDFIFLXSCAPO-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[3-[(4-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)C1 INKDFIFLXSCAPO-UHFFFAOYSA-N 0.000 claims description 2
- SKWVJQFNJFJPEY-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[4-(cyclopentylmethylsulfonylcarbamoyl)piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC2CCCC2)CC1 SKWVJQFNJFJPEY-UHFFFAOYSA-N 0.000 claims description 2
- ZUCRQMOGVUZBNG-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[4-[(2-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)F)CC1 ZUCRQMOGVUZBNG-UHFFFAOYSA-N 0.000 claims description 2
- FYMVGWKZGAPRJF-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[4-[(3,4-dichlorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(Cl)C(Cl)=CC=2)CC1 FYMVGWKZGAPRJF-UHFFFAOYSA-N 0.000 claims description 2
- DYPYIGHIYDXGEK-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[4-[(3-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(F)C=CC=2)CC1 DYPYIGHIYDXGEK-UHFFFAOYSA-N 0.000 claims description 2
- CDMBWXDZXZQMJC-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[4-[(4-cyanophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(=CC=2)C#N)CC1 CDMBWXDZXZQMJC-UHFFFAOYSA-N 0.000 claims description 2
- PFRJJPRYPPSTTF-UHFFFAOYSA-N propan-2-yl 5-cyano-6-[4-[(4-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)CC1 PFRJJPRYPPSTTF-UHFFFAOYSA-N 0.000 claims description 2
- ARFZRWISZINNNR-UHFFFAOYSA-N propan-2-yl 6-[3-[(4-chlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OC(C)C)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(Cl)=CC=2)C1 ARFZRWISZINNNR-UHFFFAOYSA-N 0.000 claims description 2
- DODYDHMHHGWWGQ-UHFFFAOYSA-N propan-2-yl 6-[4-[(3-chlorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(Cl)C=CC=2)CC1 DODYDHMHHGWWGQ-UHFFFAOYSA-N 0.000 claims description 2
- TUOCRMZGEFDPOU-UHFFFAOYSA-N propan-2-yl 6-[4-[(4-chlorophenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(Cl)=CC=2)CC1 TUOCRMZGEFDPOU-UHFFFAOYSA-N 0.000 claims description 2
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- ODXKQOYAABSACF-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-(naphthalen-2-ylsulfonylcarbamoyl)azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)C1 ODXKQOYAABSACF-UHFFFAOYSA-N 0.000 description 1
- FMCPDGJXGCZONT-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-[(2-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)F)C1 FMCPDGJXGCZONT-UHFFFAOYSA-N 0.000 description 1
- GUKUJHDWNLRSNF-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-[(3-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(F)C=CC=2)C1 GUKUJHDWNLRSNF-UHFFFAOYSA-N 0.000 description 1
- PPJHARQESKNWCF-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-[(3-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)C1 PPJHARQESKNWCF-UHFFFAOYSA-N 0.000 description 1
- ZTQQKXJLPRURAO-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-[(4-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)C1 ZTQQKXJLPRURAO-UHFFFAOYSA-N 0.000 description 1
- KLCJXTIZCVMMGY-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-[(4-methylcyclohexyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC2CCC(C)CC2)C1 KLCJXTIZCVMMGY-UHFFFAOYSA-N 0.000 description 1
- OMDKKEVWIHKEEV-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-[(4-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)C1 OMDKKEVWIHKEEV-UHFFFAOYSA-N 0.000 description 1
- YFYMJOIIISMQET-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-[[2-(trifluoromethoxy)phenyl]sulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)OC(F)(F)F)C1 YFYMJOIIISMQET-UHFFFAOYSA-N 0.000 description 1
- ZAJYCTKQIDUVJL-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[3-[[4-(trifluoromethoxy)phenyl]sulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=CC(OC(F)(F)F)=CC=2)C1 ZAJYCTKQIDUVJL-UHFFFAOYSA-N 0.000 description 1
- ZTPBHGBCOAWLCY-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-(naphthalen-2-ylsulfonylcarbamoyl)piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CC1 ZTPBHGBCOAWLCY-UHFFFAOYSA-N 0.000 description 1
- BAIDUMGYUIAEPO-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-[(2-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)F)CC1 BAIDUMGYUIAEPO-UHFFFAOYSA-N 0.000 description 1
- SBIGQDKXWCADBI-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-[(3-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(F)C=CC=2)CC1 SBIGQDKXWCADBI-UHFFFAOYSA-N 0.000 description 1
- TVOVUWORVOBYGC-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-[(3-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)CC1 TVOVUWORVOBYGC-UHFFFAOYSA-N 0.000 description 1
- ISNUTILUWOQWQG-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-[(4-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)CC1 ISNUTILUWOQWQG-UHFFFAOYSA-N 0.000 description 1
- JVZODDIDPJHVBZ-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-[(4-methylcyclohexyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC2CCC(C)CC2)CC1 JVZODDIDPJHVBZ-UHFFFAOYSA-N 0.000 description 1
- ZLHNIYLZWMTYJR-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-[(4-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)CC1 ZLHNIYLZWMTYJR-UHFFFAOYSA-N 0.000 description 1
- UNCOVKUTQZIYMT-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-[[2-(trifluoromethoxy)phenyl]sulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)OC(F)(F)F)CC1 UNCOVKUTQZIYMT-UHFFFAOYSA-N 0.000 description 1
- PKSIURDBXVHNSM-UHFFFAOYSA-N ethyl 5-cyano-2-(difluoromethyl)-6-[4-[[4-(trifluoromethoxy)phenyl]sulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=CC(OC(F)(F)F)=CC=2)CC1 PKSIURDBXVHNSM-UHFFFAOYSA-N 0.000 description 1
- VCFKBPVOZDKGKF-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[3-[(2-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)F)C1 VCFKBPVOZDKGKF-UHFFFAOYSA-N 0.000 description 1
- UEYXORSOHLORAU-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[3-[(3-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(F)C=CC=2)C1 UEYXORSOHLORAU-UHFFFAOYSA-N 0.000 description 1
- YWULDQFLQQFPEP-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[3-[(3-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)C1 YWULDQFLQQFPEP-UHFFFAOYSA-N 0.000 description 1
- LLVYZRBWFJQHAE-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[3-[(4-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)C1 LLVYZRBWFJQHAE-UHFFFAOYSA-N 0.000 description 1
- JKDXEHAGOUJCHY-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[3-[(4-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)C1 JKDXEHAGOUJCHY-UHFFFAOYSA-N 0.000 description 1
- AMXHRTVTRUOFEM-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[4-[(2-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)F)CC1 AMXHRTVTRUOFEM-UHFFFAOYSA-N 0.000 description 1
- OEVMHGXGLUDGCQ-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[4-[(3-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(F)C=CC=2)CC1 OEVMHGXGLUDGCQ-UHFFFAOYSA-N 0.000 description 1
- NLUCNOPWTWZCSP-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[4-[(3-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)CC1 NLUCNOPWTWZCSP-UHFFFAOYSA-N 0.000 description 1
- MBDYFVRISRMQIO-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[4-[(4-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)CC1 MBDYFVRISRMQIO-UHFFFAOYSA-N 0.000 description 1
- HKRQOSXBSYAYEB-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[4-[(4-methylcyclohexyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC2CCC(C)CC2)CC1 HKRQOSXBSYAYEB-UHFFFAOYSA-N 0.000 description 1
- FRKIGERIWLAXMA-UHFFFAOYSA-N ethyl 5-cyano-2-(fluoromethyl)-6-[4-[(4-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)CC1 FRKIGERIWLAXMA-UHFFFAOYSA-N 0.000 description 1
- IOLBWJSAKBJQIK-UHFFFAOYSA-N ethyl 5-cyano-2-methyl-6-[3-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-1-yl]pyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)OC(C)(C)C)C1 IOLBWJSAKBJQIK-UHFFFAOYSA-N 0.000 description 1
- HFDXYSIVHUUJDT-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,4-dichlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC(Cl)=CC=2)Cl)C1 HFDXYSIVHUUJDT-UHFFFAOYSA-N 0.000 description 1
- JEBPPHZTZMFYNX-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,4-dichlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(fluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC(Cl)=CC=2)Cl)C1 JEBPPHZTZMFYNX-UHFFFAOYSA-N 0.000 description 1
- ZBXKSBOSSZQTSB-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2,4-dichlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC(Cl)=CC=2)Cl)C1 ZBXKSBOSSZQTSB-UHFFFAOYSA-N 0.000 description 1
- HPGLTNVPDIWFFB-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2-cyanophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)C#N)C1 HPGLTNVPDIWFFB-UHFFFAOYSA-N 0.000 description 1
- VZCPZIYFBFGRIA-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(2-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)F)C1 VZCPZIYFBFGRIA-UHFFFAOYSA-N 0.000 description 1
- ALPDTRFVRYGGKT-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3,4-difluorophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(F)C(F)=CC=2)C1 ALPDTRFVRYGGKT-UHFFFAOYSA-N 0.000 description 1
- LZZOSNXVRHKXKH-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3-cyanophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=C(C=CC=2)C#N)C1 LZZOSNXVRHKXKH-UHFFFAOYSA-N 0.000 description 1
- TWFDGCKJCVVUMB-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(F)C=CC=2)C1 TWFDGCKJCVVUMB-UHFFFAOYSA-N 0.000 description 1
- RKRIFAVRMHCSIT-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(3-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)C1 RKRIFAVRMHCSIT-UHFFFAOYSA-N 0.000 description 1
- WQVKKUWNBZNTHL-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-cyanophenyl)sulfonylcarbamoyl]azetidin-1-yl]-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)C=2C=CC(=CC=2)C#N)C1 WQVKKUWNBZNTHL-UHFFFAOYSA-N 0.000 description 1
- OLRFNERNMJTCFN-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-ethylphenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(CC)=CC=2)C1 OLRFNERNMJTCFN-UHFFFAOYSA-N 0.000 description 1
- IVOXUFVCRLLPKV-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-fluorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)C1 IVOXUFVCRLLPKV-UHFFFAOYSA-N 0.000 description 1
- HGHPWWSOBOPMPY-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[(4-methylphenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)C1 HGHPWWSOBOPMPY-UHFFFAOYSA-N 0.000 description 1
- IATQXABBGIANKP-UHFFFAOYSA-N ethyl 5-cyano-6-[3-[2-oxo-2-(2-phenylethylsulfonylamino)ethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(CC(=O)NS(=O)(=O)CCC=2C=CC=CC=2)CC1 IATQXABBGIANKP-UHFFFAOYSA-N 0.000 description 1
- JXTJCPBRVZBBGV-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(2,4-dichlorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC(Cl)=CC=2)Cl)CC1 JXTJCPBRVZBBGV-UHFFFAOYSA-N 0.000 description 1
- BAPNECPTYFRZCU-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(2,4-dichlorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-(fluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC(Cl)=CC=2)Cl)CC1 BAPNECPTYFRZCU-UHFFFAOYSA-N 0.000 description 1
- JLLSINBRRFVVHR-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(2,4-dichlorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC(Cl)=CC=2)Cl)CC1 JLLSINBRRFVVHR-UHFFFAOYSA-N 0.000 description 1
- PKZUYAOLJCGVGE-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(2-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)F)CC1 PKZUYAOLJCGVGE-UHFFFAOYSA-N 0.000 description 1
- JIBRPVVVWZRXDA-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(3-cyanophenyl)sulfonylcarbamoyl]piperidin-1-yl]-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=C(C=CC=2)C#N)CC1 JIBRPVVVWZRXDA-UHFFFAOYSA-N 0.000 description 1
- VRXDSTXQMKIGSN-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(3-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(F)C=CC=2)CC1 VRXDSTXQMKIGSN-UHFFFAOYSA-N 0.000 description 1
- OOJYYOXDEDQMPL-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(3-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(C)C=CC=2)CC1 OOJYYOXDEDQMPL-UHFFFAOYSA-N 0.000 description 1
- XNQQDRFQFDFUKY-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-cyanophenyl)sulfonylcarbamoyl]piperidin-1-yl]-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)C=2C=CC(=CC=2)C#N)CC1 XNQQDRFQFDFUKY-UHFFFAOYSA-N 0.000 description 1
- ZKRINNSKLLABDY-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-fluorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(F)=CC=2)CC1 ZKRINNSKLLABDY-UHFFFAOYSA-N 0.000 description 1
- LMMAPNCJSSIUOS-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-fluorophenyl)methylsulfonylcarbamoyl]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)CC=2C=CC(F)=CC=2)CC1 LMMAPNCJSSIUOS-UHFFFAOYSA-N 0.000 description 1
- DBAOAOZGDFXAPN-UHFFFAOYSA-N ethyl 5-cyano-6-[4-[(4-methylphenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC(C)=CC=2)CC1 DBAOAOZGDFXAPN-UHFFFAOYSA-N 0.000 description 1
- NXBDPGUARQXOEX-UHFFFAOYSA-N ethyl 6-(3-aminoazetidin-1-yl)-5-cyano-2-methylpyridine-3-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.N1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CC(N)C1 NXBDPGUARQXOEX-UHFFFAOYSA-N 0.000 description 1
- VTRJTFHSMINAKB-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 VTRJTFHSMINAKB-UHFFFAOYSA-N 0.000 description 1
- XVSJZDQQRYCJKB-UHFFFAOYSA-N ethyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-(fluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 XVSJZDQQRYCJKB-UHFFFAOYSA-N 0.000 description 1
- VXMFIXNJAQNUIV-UHFFFAOYSA-N ethyl 6-[3-(butylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound C1C(C(=O)NS(=O)(=O)CCCC)CN1C1=NC(C(F)F)=C(C(=O)OCC)C=C1C#N VXMFIXNJAQNUIV-UHFFFAOYSA-N 0.000 description 1
- INASUZBBYRYNGS-UHFFFAOYSA-N ethyl 6-[3-[(2-chlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)Cl)C1 INASUZBBYRYNGS-UHFFFAOYSA-N 0.000 description 1
- QSQAWDAGUFOSAA-UHFFFAOYSA-N ethyl 6-[3-[(2-chlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-(fluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)Cl)C1 QSQAWDAGUFOSAA-UHFFFAOYSA-N 0.000 description 1
- MMGYQZFQELUPKV-UHFFFAOYSA-N ethyl 6-[3-[(2-chlorophenyl)methylsulfonylcarbamoyl]azetidin-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(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)Cl)C1 MMGYQZFQELUPKV-UHFFFAOYSA-N 0.000 description 1
- BSBAVMGAYNNNMU-UHFFFAOYSA-N ethyl 6-[3-[(3-chlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(Cl)C=CC=2)C1 BSBAVMGAYNNNMU-UHFFFAOYSA-N 0.000 description 1
- WIQSVAKDPPAKTR-UHFFFAOYSA-N ethyl 6-[3-[(3-chlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-(fluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=C(Cl)C=CC=2)C1 WIQSVAKDPPAKTR-UHFFFAOYSA-N 0.000 description 1
- PECXZSSVLFSZDJ-UHFFFAOYSA-N ethyl 6-[3-[(3-chlorophenyl)methylsulfonylcarbamoyl]azetidin-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(C(=O)NS(=O)(=O)CC=2C=C(Cl)C=CC=2)C1 PECXZSSVLFSZDJ-UHFFFAOYSA-N 0.000 description 1
- VCUDZGXIZZSNFY-UHFFFAOYSA-N ethyl 6-[3-[(4-chlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(Cl)=CC=2)C1 VCUDZGXIZZSNFY-UHFFFAOYSA-N 0.000 description 1
- JXMYVAPFVJBNKQ-UHFFFAOYSA-N ethyl 6-[3-[(4-chlorophenyl)methylsulfonylcarbamoyl]azetidin-1-yl]-5-cyano-2-(fluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC(Cl)=CC=2)C1 JXMYVAPFVJBNKQ-UHFFFAOYSA-N 0.000 description 1
- DMHHLQDNINBLAE-UHFFFAOYSA-N ethyl 6-[3-[(4-chlorophenyl)methylsulfonylcarbamoyl]azetidin-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(C(=O)NS(=O)(=O)CC=2C=CC(Cl)=CC=2)C1 DMHHLQDNINBLAE-UHFFFAOYSA-N 0.000 description 1
- IKUFXVUEOKBWRQ-UHFFFAOYSA-N ethyl 6-[3-[2-(benzylsulfonylamino)-2-oxoethyl]azetidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CC(CC(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 IKUFXVUEOKBWRQ-UHFFFAOYSA-N 0.000 description 1
- ZBODIIMSRYUGBE-UHFFFAOYSA-N ethyl 6-[3-[2-(benzylsulfonylamino)-2-oxoethyl]pyrrolidin-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(CC(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 ZBODIIMSRYUGBE-UHFFFAOYSA-N 0.000 description 1
- ABZPNJLQUVSKKT-UHFFFAOYSA-N ethyl 6-[3-[2-[(5-chlorothiophen-2-yl)sulfonylamino]-2-oxoethyl]pyrrolidin-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(CC(=O)NS(=O)(=O)C=2SC(Cl)=CC=2)CC1 ABZPNJLQUVSKKT-UHFFFAOYSA-N 0.000 description 1
- PRVVDXMDRTTWIS-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)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)CC=2C=CC=CC=2)CC1 PRVVDXMDRTTWIS-UHFFFAOYSA-N 0.000 description 1
- JCHYOSBJFAHDTK-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 JCHYOSBJFAHDTK-UHFFFAOYSA-N 0.000 description 1
- DUXHTJWBIKBPRM-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-(fluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 DUXHTJWBIKBPRM-UHFFFAOYSA-N 0.000 description 1
- KILRWBDQDRZMLK-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 KILRWBDQDRZMLK-UHFFFAOYSA-N 0.000 description 1
- NCKCXIUOOHBJPL-UHFFFAOYSA-N ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methyl-1-oxidopyridin-1-ium-3-carboxylate Chemical compound [O-][N+]1=C(C)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)CC1 NCKCXIUOOHBJPL-UHFFFAOYSA-N 0.000 description 1
- CHLZZYFAPMCPFL-UHFFFAOYSA-N ethyl 6-[4-(butylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound C1CC(C(=O)NS(=O)(=O)CCCC)CCN1C1=NC(C(F)F)=C(C(=O)OCC)C=C1C#N CHLZZYFAPMCPFL-UHFFFAOYSA-N 0.000 description 1
- NQRLLCMUTSZWKR-UHFFFAOYSA-N ethyl 6-[4-[(2-chlorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)Cl)CC1 NQRLLCMUTSZWKR-UHFFFAOYSA-N 0.000 description 1
- DUDDAAYGALWKPO-UHFFFAOYSA-N ethyl 6-[4-[(2-chlorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-(fluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(CF)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)Cl)CC1 DUDDAAYGALWKPO-UHFFFAOYSA-N 0.000 description 1
- XWTQVMBAGJEEBX-UHFFFAOYSA-N ethyl 6-[4-[(2-chlorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-(trifluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C(=CC=CC=2)Cl)CC1 XWTQVMBAGJEEBX-UHFFFAOYSA-N 0.000 description 1
- KSDUUXIKUZKXAU-UHFFFAOYSA-N ethyl 6-[4-[(3-bromophenyl)methylsulfonylcarbamoyl]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)CC=2C=C(Br)C=CC=2)CC1 KSDUUXIKUZKXAU-UHFFFAOYSA-N 0.000 description 1
- PLOABHZTHSFQJZ-UHFFFAOYSA-N ethyl 6-[4-[(3-chlorophenyl)methylsulfonylcarbamoyl]piperidin-1-yl]-5-cyano-2-(difluoromethyl)pyridine-3-carboxylate Chemical compound N1=C(C(F)F)C(C(=O)OCC)=CC(C#N)=C1N1CCC(C(=O)NS(=O)(=O)CC=2C=C(Cl)C=CC=2)CC1 PLOABHZTHSFQJZ-UHFFFAOYSA-N 0.000 description 1
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- PZWOEPBNJKUCEZ-UHFFFAOYSA-N propan-2-yl 6-[4-[(2-chlorophenyl)methylsulfonylcarbamoyl]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)CC=2C(=CC=CC=2)Cl)CC1 PZWOEPBNJKUCEZ-UHFFFAOYSA-N 0.000 description 1
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- XVLFWTQTUQZDJX-UHFFFAOYSA-N propyl 6-[3-(benzylsulfonylcarbamoyl)azetidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate Chemical compound N1=C(C)C(C(=O)OCCC)=CC(C#N)=C1N1CC(C(=O)NS(=O)(=O)CC=2C=CC=CC=2)C1 XVLFWTQTUQZDJX-UHFFFAOYSA-N 0.000 description 1
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- 159000000000 sodium salts Chemical class 0.000 description 1
- YICFALDKKMHFLT-UHFFFAOYSA-M sodium;3-methoxy-3-oxopropane-1-sulfinate Chemical compound [Na+].COC(=O)CCS([O-])=O YICFALDKKMHFLT-UHFFFAOYSA-M 0.000 description 1
- XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 1
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- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
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- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
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- Life Sciences & Earth Sciences (AREA)
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- Dermatology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (4)
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| SE0501663-9 | 2005-07-13 | ||
| SE0501663 | 2005-07-13 | ||
| SE0502354 | 2005-10-24 | ||
| SE0502354-4 | 2005-10-24 |
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| KR20080039405A true KR20080039405A (ko) | 2008-05-07 |
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| KR1020087002914A Withdrawn KR20080039405A (ko) | 2005-07-13 | 2006-07-04 | 신규한 피리딘 유사체 |
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| EP (1) | EP1904474A4 (enExample) |
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| CA (1) | CA2614726A1 (enExample) |
| EC (1) | ECSP088140A (enExample) |
| IL (1) | IL188293A0 (enExample) |
| MX (1) | MX2008000470A (enExample) |
| NO (1) | NO20076682L (enExample) |
| RU (1) | RU2008101924A (enExample) |
| TW (1) | TW200726758A (enExample) |
| UY (1) | UY29667A1 (enExample) |
| WO (1) | WO2007008140A1 (enExample) |
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|---|---|---|---|---|
| JP2009542641A (ja) * | 2006-07-04 | 2009-12-03 | アストラゼネカ アクチボラグ | 新規ピリジン類縁体 |
| US20080027103A1 (en) * | 2006-07-04 | 2008-01-31 | Astrazeneca Ab | Novel Crystalline Forms 1 |
| US20080176827A1 (en) * | 2007-01-12 | 2008-07-24 | Astrazeneca Ab | New Pyridine Analogues VII 543 |
| RU2009123928A (ru) * | 2007-01-12 | 2011-02-20 | Астразенека Аб (Se) | Пиридиновые соединения и их применение в качестве антагонистов p2y12 |
| US20080200448A1 (en) * | 2007-01-12 | 2008-08-21 | Astrazeneca Ab | New Pyridine Analogues VIII 518 |
| US20090018166A1 (en) * | 2007-07-13 | 2009-01-15 | Astrazeneca Ab | New Pyridine Analogues X 161 |
| AR074628A1 (es) * | 2008-07-07 | 2011-02-02 | Astrazeneca Ab | Derivados de piridina 2- amino-6-alquil sustituidos utiles como inhibidores de p2y12 308 |
| WO2010005384A1 (en) * | 2008-07-07 | 2010-01-14 | Astrazeneca Ab | Ketone pyridine analogues and their use in the treatment of cardiovascular disorders |
| JP2014051434A (ja) * | 2010-12-28 | 2014-03-20 | Dainippon Sumitomo Pharma Co Ltd | 二環性ピリミジン誘導体 |
| WO2013033178A1 (en) | 2011-08-30 | 2013-03-07 | University Of Utah Research Foundation | Methods and compositions for treating nephrogenic diabetes insipidus |
| CN103483274B (zh) * | 2013-09-25 | 2016-03-09 | 江苏快达农化股份有限公司 | 一种制备苄嘧磺隆的方法 |
| WO2017022861A1 (ja) | 2015-08-06 | 2017-02-09 | 宇部興産株式会社 | 置換グアニジン誘導体 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6156758A (en) * | 1999-09-08 | 2000-12-05 | Isis Pharmaceuticals, Inc. | Antibacterial quinazoline compounds |
| DE60114994T2 (de) * | 2000-02-04 | 2006-08-03 | Portola Pharmaceuticals, Inc., South San Francisco | Blutplättchen-adp-rezeptor-inhibitoren |
| US6906063B2 (en) * | 2000-02-04 | 2005-06-14 | Portola Pharmaceuticals, Inc. | Platelet ADP receptor inhibitors |
| US7132408B2 (en) * | 2000-08-21 | 2006-11-07 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
| US7018985B1 (en) * | 2000-08-21 | 2006-03-28 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
| US7452870B2 (en) * | 2000-08-21 | 2008-11-18 | Inspire Pharmaceuticals, Inc. | Drug-eluting stents coated with P2Y12 receptor antagonist compound |
| FR2820057A1 (fr) * | 2001-01-30 | 2002-08-02 | Ct De Transfert De Technologie | Membrane pour chambre d'encapsulation de cellules produisant au moins une substance biologiquement active et organe bio-artificiel comprenant une telle membrane |
| AR037097A1 (es) * | 2001-10-05 | 2004-10-20 | Novartis Ag | Compuestos acilsulfonamidas, composiciones farmaceuticas y el uso de dichos compuestos para la preparacion de un medicamento |
| KR101010905B1 (ko) * | 2002-01-18 | 2011-01-25 | 아스텔라스세이야쿠 가부시키가이샤 | 2-아실아미노티아졸 유도체 또는 그 염 |
| GB0312609D0 (en) * | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
| JP4879745B2 (ja) * | 2003-10-03 | 2012-02-22 | ポートラ ファーマシューティカルズ， インコーポレイテッド | 置換イソキノリノン |
| US7335648B2 (en) * | 2003-10-21 | 2008-02-26 | Inspire Pharmaceuticals, Inc. | Non-nucleotide composition and method for inhibiting platelet aggregation |
| US7504497B2 (en) * | 2003-10-21 | 2009-03-17 | Inspire Pharmaceuticals, Inc. | Orally bioavailable compounds and methods for inhibiting platelet aggregation |
| US7749981B2 (en) * | 2003-10-21 | 2010-07-06 | Inspire Pharmaceuticals, Inc. | Drug-eluting stents coated with non-nucleotide P2Y12 receptor antagonist compound |
| WO2005056354A2 (en) * | 2003-12-03 | 2005-06-23 | Gedeon Anthony A | Method of resisting contaminant build up and oxidation of vehicle surfaces and other surfaces |
| BRPI0512535A (pt) * | 2004-06-24 | 2008-03-25 | Incyte Corp | compostos de piperidinas n-substituìdas, suas composições e métodos de modulações |
| RU2007129779A (ru) * | 2005-01-06 | 2009-02-20 | Астразенека Аб (Se) | Новые соединения пиридина |
| EP2041115A4 (en) * | 2006-07-04 | 2010-07-07 | Astrazeneca Ab | NEW PYRIDINE ANALOG |
| JP2009542641A (ja) * | 2006-07-04 | 2009-12-03 | アストラゼネカ アクチボラグ | 新規ピリジン類縁体 |
| WO2008004943A1 (en) * | 2006-07-04 | 2008-01-10 | Astrazeneca Ab | New pyridine analogues |
-
2006
- 2006-07-04 MX MX2008000470A patent/MX2008000470A/es not_active Application Discontinuation
- 2006-07-04 JP JP2008521353A patent/JP2009501216A/ja active Pending
- 2006-07-04 KR KR1020087002914A patent/KR20080039405A/ko not_active Withdrawn
- 2006-07-04 RU RU2008101924/04A patent/RU2008101924A/ru not_active Application Discontinuation
- 2006-07-04 AU AU2006267148A patent/AU2006267148A1/en not_active Abandoned
- 2006-07-04 WO PCT/SE2006/000832 patent/WO2007008140A1/en not_active Ceased
- 2006-07-04 CA CA002614726A patent/CA2614726A1/en not_active Abandoned
- 2006-07-04 EP EP06758023A patent/EP1904474A4/en not_active Withdrawn
- 2006-07-04 US US11/995,326 patent/US20080312208A1/en not_active Abandoned
- 2006-07-12 UY UY29667A patent/UY29667A1/es not_active Application Discontinuation
- 2006-07-12 AR ARP060102992A patent/AR054632A1/es not_active Application Discontinuation
- 2006-07-13 TW TW095125590A patent/TW200726758A/zh unknown
-
2007
- 2007-12-20 IL IL188293A patent/IL188293A0/en unknown
- 2007-12-28 NO NO20076682A patent/NO20076682L/no not_active Application Discontinuation
-
2008
- 2008-01-25 EC EC2008008140A patent/ECSP088140A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2008101924A (ru) | 2009-08-20 |
| JP2009501216A (ja) | 2009-01-15 |
| AR054632A1 (es) | 2007-07-04 |
| TW200726758A (en) | 2007-07-16 |
| NO20076682L (no) | 2008-03-05 |
| WO2007008140A1 (en) | 2007-01-18 |
| EP1904474A1 (en) | 2008-04-02 |
| ECSP088140A (es) | 2008-02-20 |
| MX2008000470A (es) | 2008-03-11 |
| UY29667A1 (es) | 2007-02-28 |
| AU2006267148A1 (en) | 2007-01-18 |
| IL188293A0 (en) | 2008-04-13 |
| EP1904474A4 (en) | 2010-06-16 |
| CA2614726A1 (en) | 2007-01-18 |
| US20080312208A1 (en) | 2008-12-18 |
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