JP2022519301A - Ｎ－（ピリジン－２－イル）ピリジン－スルホンアミド誘導体及び疾患の処置におけるそれらの使用 - Google Patents

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Publication number

JP2022519301A

JP2022519301A JP2021545808A JP2021545808A JP2022519301A JP 2022519301 A JP2022519301 A JP 2022519301A JP 2021545808 A JP2021545808 A JP 2021545808A JP 2021545808 A JP2021545808 A JP 2021545808A JP 2022519301 A JP2022519301 A JP 2022519301A

Authority

JP

Japan

Prior art keywords

pyridin

sulfamoyl

trifluoromethyl

amino

acid

Prior art date

2019-02-06

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Withdrawn

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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 49
• 201000010099 disease Diseases 0.000 title claims abstract description 36
• 238000011282 treatment Methods 0.000 title abstract description 35
• HGLLHXBAIVABRJ-UHFFFAOYSA-N n-pyridin-2-ylpyridine-2-sulfonamide Chemical class C=1C=CC=NC=1S(=O)(=O)NC1=CC=CC=N1 HGLLHXBAIVABRJ-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 298
• 238000000034 method Methods 0.000 claims abstract description 195
• 201000003883 Cystic fibrosis Diseases 0.000 claims abstract description 40
• 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 claims abstract description 38
• 238000004519 manufacturing process Methods 0.000 claims abstract description 4
• 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 claims abstract 27
• -1 pyridine-2-yl Chemical group 0.000 claims description 563
• 150000003839 salts Chemical class 0.000 claims description 259
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 186
• 125000000217 alkyl group Chemical group 0.000 claims description 137
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 134
• 239000002253 acid Substances 0.000 claims description 96
• 239000000203 mixture Substances 0.000 claims description 94
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 89
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 79
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 75
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 70
• 229910052739 hydrogen Inorganic materials 0.000 claims description 66
• 125000003545 alkoxy group Chemical group 0.000 claims description 62
• 235000011054 acetic acid Nutrition 0.000 claims description 61
• 125000005843 halogen group Chemical group 0.000 claims description 61
• 235000019260 propionic acid Nutrition 0.000 claims description 59
• 229910052805 deuterium Inorganic materials 0.000 claims description 53
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 52
• 229910052760 oxygen Inorganic materials 0.000 claims description 50
• 229910052717 sulfur Inorganic materials 0.000 claims description 48
• 229910052799 carbon Inorganic materials 0.000 claims description 47
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
• 125000005842 heteroatom Chemical group 0.000 claims description 44
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 42
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 33
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 32
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 31
• 239000008194 pharmaceutical composition Substances 0.000 claims description 31
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 28
• 239000003814 drug Substances 0.000 claims description 25
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 25
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 23
• 208000006673 asthma Diseases 0.000 claims description 21
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 21
• 230000001404 mediated effect Effects 0.000 claims description 20
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 19
• 229910052801 chlorine Inorganic materials 0.000 claims description 18
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 17
• 125000002619 bicyclic group Chemical group 0.000 claims description 15
• 229910052731 fluorine Inorganic materials 0.000 claims description 15
• 125000004076 pyridyl group Chemical group 0.000 claims description 15
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
• RWMANLVVOREYOR-UHFFFAOYSA-N 3-[1-[6-[[6-(2-ethenylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-3-yl]propanoic acid Chemical compound FC(C=1C=CC(=NC=1C1=C(C=CC=C1)C=C)NS(=O)(=O)C1=CC=CC(=N1)N1CC(CCC1)CCC(=O)O)(F)F RWMANLVVOREYOR-UHFFFAOYSA-N 0.000 claims description 12
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
• 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 12
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 12
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 11
• 229940079593 drug Drugs 0.000 claims description 11
• 125000001072 heteroaryl group Chemical group 0.000 claims description 11
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
• CJDCZPBJTCVPMM-UHFFFAOYSA-N 4-[[6-[[5-chloro-6-(2,6-dimethylphenyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound ClC=1C=CC(=NC=1C1=C(C=CC=C1C)C)NS(=O)(=O)C1=CC=CC(=N1)NCCCC(=O)O CJDCZPBJTCVPMM-UHFFFAOYSA-N 0.000 claims description 10
• 239000005711 Benzoic acid Substances 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
• 235000010233 benzoic acid Nutrition 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 10
• 239000003795 chemical substances by application Substances 0.000 claims description 9
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 9
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 9
• VQFHRZUPJUWXEX-UHFFFAOYSA-N 1-[[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]methyl]cyclobutane-1-carboxylic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)NCC1(CCC1)C(=O)O)C(F)(F)F)C VQFHRZUPJUWXEX-UHFFFAOYSA-N 0.000 claims description 7
• LBVGKZMVSBNQCH-UHFFFAOYSA-N 1-[[methyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]methyl]cyclobutane-1-carboxylic acid Chemical compound CN(C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)CC1(CCC1)C(=O)O LBVGKZMVSBNQCH-UHFFFAOYSA-N 0.000 claims description 7
• QNYMOTIHUOJTAJ-UHFFFAOYSA-N 2-[3-methyl-1-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]pyrrolidin-3-yl]acetic acid Chemical compound CC1(CN(CC1)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)CC(=O)O QNYMOTIHUOJTAJ-UHFFFAOYSA-N 0.000 claims description 7
• ZUWJWKLNDDMVMG-UHFFFAOYSA-N 2-[4-methyl-1-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound CC1(CCN(CC1)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)CC(=O)O ZUWJWKLNDDMVMG-UHFFFAOYSA-N 0.000 claims description 7
• QPLPYAAEHXFRDG-UHFFFAOYSA-N 3-[cyclopropylmethyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C1(CC1)CN(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O QPLPYAAEHXFRDG-UHFFFAOYSA-N 0.000 claims description 7
• UQQUZNUNKANDOB-UHFFFAOYSA-N 3-[ethyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C(C)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O UQQUZNUNKANDOB-UHFFFAOYSA-N 0.000 claims description 7
• UVYNKWPVQBFPBP-UHFFFAOYSA-N 4-[ethyl-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound C(C)N(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC(=C1)F)C)(=O)=O UVYNKWPVQBFPBP-UHFFFAOYSA-N 0.000 claims description 7
• LRKSROWBSOYZNJ-UHFFFAOYSA-N 5-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-propan-2-ylamino]pentanoic acid Chemical compound C(C)(C)N(CCCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O LRKSROWBSOYZNJ-UHFFFAOYSA-N 0.000 claims description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
• 125000002950 monocyclic group Chemical group 0.000 claims description 7
• BTIQZYJNXQVPMM-UHFFFAOYSA-N 1-[[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]methyl]cyclopropane-1-carboxylic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)NCC1(CC1)C(=O)O)C(F)(F)F)C BTIQZYJNXQVPMM-UHFFFAOYSA-N 0.000 claims description 6
• QSULYEMTQVPKIK-UHFFFAOYSA-N 2,2-dimethyl-3-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound CC(C(=O)O)(CNC1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)C QSULYEMTQVPKIK-UHFFFAOYSA-N 0.000 claims description 6
• LBZHCVCMDZGZJS-UHFFFAOYSA-N 2,2-dimethyl-3-[methyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound CC(C(=O)O)(CN(C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)C)C LBZHCVCMDZGZJS-UHFFFAOYSA-N 0.000 claims description 6
• XRVBAIXODRVCCF-UHFFFAOYSA-N 3-[[4-[[5-chloro-6-(2,6-dimethylphenyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound ClC=1C=CC(=NC=1C1=C(C=CC=C1C)C)NS(=O)(=O)C1=CC(=NC=C1)NC(CC(=O)O)C XRVBAIXODRVCCF-UHFFFAOYSA-N 0.000 claims description 6
• FHSBNAAMGSZBSI-UHFFFAOYSA-N 3-[[4-[[5-chloro-6-(2,6-dimethylphenyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]pentanoic acid Chemical compound ClC=1C=CC(=NC=1C1=C(C=CC=C1C)C)NS(=O)(=O)C1=CC(=NC=C1)NC(CC(=O)O)CC FHSBNAAMGSZBSI-UHFFFAOYSA-N 0.000 claims description 6
• NFZCBKUGTKMOEI-UHFFFAOYSA-N 3-[[6-[[6-(2-cyclopropyl-5-fluorophenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-ethylamino]propanoic acid Chemical compound C1(CC1)C1=C(C=C(C=C1)F)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N(CCC(=O)O)CC)C(F)(F)F NFZCBKUGTKMOEI-UHFFFAOYSA-N 0.000 claims description 6
• QHXHKOFQHZHDOV-UHFFFAOYSA-N 3-[[6-[[6-(2-cyclopropylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-methylamino]propanoic acid Chemical compound C1(CC1)C1=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N(CCC(=O)O)C)C(F)(F)F QHXHKOFQHZHDOV-UHFFFAOYSA-N 0.000 claims description 6
• PJJKWDJMPCGRJR-UHFFFAOYSA-N 3-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-(2-methylpropyl)amino]propanoic acid Chemical compound C(C(C)C)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O PJJKWDJMPCGRJR-UHFFFAOYSA-N 0.000 claims description 6
• LDPODUGBNHDZCA-UHFFFAOYSA-N 3-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-propylamino]propanoic acid Chemical compound C(CC)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O LDPODUGBNHDZCA-UHFFFAOYSA-N 0.000 claims description 6
• GFSJYHATZVAPHM-UHFFFAOYSA-N 3-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)NCCC(=O)O)C(F)(F)F)C GFSJYHATZVAPHM-UHFFFAOYSA-N 0.000 claims description 6
• RORMSAUVNSLNLG-UHFFFAOYSA-N 3-[cyclopropyl-[6-[[6-(2-ethyl-5-fluorophenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C1(CC1)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC(=C1)F)CC)(=O)=O RORMSAUVNSLNLG-UHFFFAOYSA-N 0.000 claims description 6
• RLNMJFRTOMICIY-UHFFFAOYSA-N 3-[ethyl-[6-[[6-(2-ethyl-5-fluorophenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C(C)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC(=C1)F)CC)(=O)=O RLNMJFRTOMICIY-UHFFFAOYSA-N 0.000 claims description 6
• WEAXUNAGYRXCTG-UHFFFAOYSA-N 3-[ethyl-[6-[[6-(2-ethylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C(C)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)CC)(=O)=O WEAXUNAGYRXCTG-UHFFFAOYSA-N 0.000 claims description 6
• ONZMVGXAKUVQLT-UHFFFAOYSA-N 3-[ethyl-[6-[[6-(3-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C(C)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C(=CC=C1)F)C)(=O)=O ONZMVGXAKUVQLT-UHFFFAOYSA-N 0.000 claims description 6
• ZKRJEGXOFFFCTM-UHFFFAOYSA-N 3-[ethyl-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C(C)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC(=C1)F)C)(=O)=O ZKRJEGXOFFFCTM-UHFFFAOYSA-N 0.000 claims description 6
• FOXNCTORNDPYGL-UHFFFAOYSA-N 3-[methyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound CN(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O FOXNCTORNDPYGL-UHFFFAOYSA-N 0.000 claims description 6
• MTPLOOXHLXCFFF-UHFFFAOYSA-N 4-[6-[[6-(2-ethylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]oxycyclohexane-1-carboxylic acid Chemical compound C(C)C1=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)OC1CCC(CC1)C(=O)O)C(F)(F)F MTPLOOXHLXCFFF-UHFFFAOYSA-N 0.000 claims description 6
• YIAOIFVDMGECLY-UHFFFAOYSA-N 4-[[6-[[6-(2-cyclopropylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-methylamino]butanoic acid Chemical compound C1(CC1)C1=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N(CCCC(=O)O)C)C(F)(F)F YIAOIFVDMGECLY-UHFFFAOYSA-N 0.000 claims description 6
• UBIQZSIMUIENPW-UHFFFAOYSA-N 4-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-(2-methylpropyl)amino]butanoic acid Chemical compound C(C(C)C)N(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O UBIQZSIMUIENPW-UHFFFAOYSA-N 0.000 claims description 6
• WAAROZKWYXCNEH-UHFFFAOYSA-N 4-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-propan-2-ylamino]butanoic acid Chemical compound C(C)(C)N(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O WAAROZKWYXCNEH-UHFFFAOYSA-N 0.000 claims description 6
• ILWFJJWTRHHRGT-UHFFFAOYSA-N 4-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-propylamino]butanoic acid Chemical compound C(CC)N(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O ILWFJJWTRHHRGT-UHFFFAOYSA-N 0.000 claims description 6
• QPCLBUWESNHILS-UHFFFAOYSA-N 4-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)NCCCC(=O)O)C(F)(F)F)C QPCLBUWESNHILS-UHFFFAOYSA-N 0.000 claims description 6
• TWLQGLTXLAETFW-UHFFFAOYSA-N 4-[butyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound C(CCC)N(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O TWLQGLTXLAETFW-UHFFFAOYSA-N 0.000 claims description 6
• DGCUEAVMSLAVHD-UHFFFAOYSA-N 4-[butyl-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound C(CCC)N(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC(=C1)F)C)(=O)=O DGCUEAVMSLAVHD-UHFFFAOYSA-N 0.000 claims description 6
• IDJDZUZWSIQZTO-UHFFFAOYSA-N 4-[cyclopropylmethyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound C1(CC1)CN(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O IDJDZUZWSIQZTO-UHFFFAOYSA-N 0.000 claims description 6
• KDIRMHLDVDYWEN-UHFFFAOYSA-N 4-[ethyl-[6-[[6-(2-ethyl-5-fluorophenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound C(C)N(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC(=C1)F)CC)(=O)=O KDIRMHLDVDYWEN-UHFFFAOYSA-N 0.000 claims description 6
• BTHIYGUXUNMDHD-UHFFFAOYSA-N 4-[ethyl-[6-[[6-(2-ethylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound C(C)N(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)CC)(=O)=O BTHIYGUXUNMDHD-UHFFFAOYSA-N 0.000 claims description 6
• FKHYRLGYAZRRBK-UHFFFAOYSA-N 4-[methyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]butanoic acid Chemical compound CN(CCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O FKHYRLGYAZRRBK-UHFFFAOYSA-N 0.000 claims description 6
• XXCIBKOJWFAWRP-UHFFFAOYSA-N 4-methyl-1-[6-[[6-(2-phenoxyphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidine-4-carboxylic acid Chemical compound CC1(CCN(CC1)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)OC1=CC=CC=C1)(=O)=O)C(=O)O XXCIBKOJWFAWRP-UHFFFAOYSA-N 0.000 claims description 6
• QINNUNVTRXVUBE-UHFFFAOYSA-N 5-[[6-[[5-chloro-6-(2,6-dimethylphenyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]pentanoic acid Chemical compound ClC=1C=CC(=NC=1C1=C(C=CC=C1C)C)NS(=O)(=O)C1=CC=CC(=N1)NCCCCC(=O)O QINNUNVTRXVUBE-UHFFFAOYSA-N 0.000 claims description 6
• KHTDAARWNHRNPB-UHFFFAOYSA-N 5-[[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]pentanoic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)NCCCCC(=O)O)C(F)(F)F)C KHTDAARWNHRNPB-UHFFFAOYSA-N 0.000 claims description 6
• ZCAVMYSFXTXZBP-UHFFFAOYSA-N 5-[methyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]pentanoic acid Chemical compound CN(CCCCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O ZCAVMYSFXTXZBP-UHFFFAOYSA-N 0.000 claims description 6
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
• VRJXLHPFIPCZEQ-UHFFFAOYSA-N 1-[[[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-methylamino]methyl]cyclobutane-1-carboxylic acid Chemical compound FC=1C=CC(=C(C=1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N(C)CC1(CCC1)C(=O)O)C(F)(F)F)C VRJXLHPFIPCZEQ-UHFFFAOYSA-N 0.000 claims description 5
• ABMBLCSEZBSOSL-UHFFFAOYSA-N 1-[[methyl-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]methyl]cyclopentane-1-carboxylic acid Chemical compound CN(C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)CC1(CCCC1)C(=O)O ABMBLCSEZBSOSL-UHFFFAOYSA-N 0.000 claims description 5
• ZBYCSDICTWCSON-QGZVFWFLSA-N 2-[(3R)-1-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-3-yl]acetic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1C[C@H](CCC1)CC(=O)O)C(F)(F)F)C ZBYCSDICTWCSON-QGZVFWFLSA-N 0.000 claims description 5
• OLDDYMMDTRBMEK-RUZDIDTESA-N 2-[(3R)-1-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-3-methylpiperidin-3-yl]acetic acid Chemical compound FC=1C=CC(=C(C=1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1C[C@@](CCC1)(C)CC(=O)O)C(F)(F)F)C OLDDYMMDTRBMEK-RUZDIDTESA-N 0.000 claims description 5
• ZBYCSDICTWCSON-KRWDZBQOSA-N 2-[(3S)-1-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-3-yl]acetic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1C[C@@H](CCC1)CC(=O)O)C(F)(F)F)C ZBYCSDICTWCSON-KRWDZBQOSA-N 0.000 claims description 5
• OLDDYMMDTRBMEK-VWLOTQADSA-N 2-[(3S)-1-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-3-methylpiperidin-3-yl]acetic acid Chemical compound FC=1C=CC(=C(C=1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1C[C@](CCC1)(C)CC(=O)O)C(F)(F)F)C OLDDYMMDTRBMEK-VWLOTQADSA-N 0.000 claims description 5
• OITLVEWECCPICA-UHFFFAOYSA-N 2-[1-[6-[[5-chloro-6-(2,6-dimethylphenyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound ClC=1C=CC(=NC=1C1=C(C=CC=C1C)C)NS(=O)(=O)C1=CC=CC(=N1)N1CCC(CC1)CC(=O)O OITLVEWECCPICA-UHFFFAOYSA-N 0.000 claims description 5
• KZSDMQJCMWKWIL-UHFFFAOYSA-N 2-[1-[6-[[6-(2-phenylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-4-yl]acetic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1CCC(CC1)CC(=O)O)C(F)(F)F)C1=CC=CC=C1 KZSDMQJCMWKWIL-UHFFFAOYSA-N 0.000 claims description 5
• DPEPAVIQSPGIQK-UHFFFAOYSA-N 2-[1-[6-[[6-(2-tert-butylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-4-methylpiperidin-4-yl]acetic acid Chemical compound C(C)(C)(C)C1=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1CCC(CC1)(C)CC(=O)O)C(F)(F)F DPEPAVIQSPGIQK-UHFFFAOYSA-N 0.000 claims description 5
• DRCNXSQVYMAMQN-UHFFFAOYSA-N 2-[1-[6-[[6-(3-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-3-methylpiperidin-3-yl]acetic acid Chemical compound FC=1C(=C(C=CC=1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1CC(CCC1)(C)CC(=O)O)C(F)(F)F)C DRCNXSQVYMAMQN-UHFFFAOYSA-N 0.000 claims description 5
• KSFAZNQCXBWTNA-UHFFFAOYSA-N 2-[1-[6-[[6-(3-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-4-methylpiperidin-4-yl]acetic acid Chemical compound FC=1C(=C(C=CC=1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1CCC(CC1)(C)CC(=O)O)C(F)(F)F)C KSFAZNQCXBWTNA-UHFFFAOYSA-N 0.000 claims description 5
• OLDDYMMDTRBMEK-UHFFFAOYSA-N 2-[1-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-3-methylpiperidin-3-yl]acetic acid Chemical compound FC=1C=CC(=C(C=1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1CC(CCC1)(C)CC(=O)O)C(F)(F)F)C OLDDYMMDTRBMEK-UHFFFAOYSA-N 0.000 claims description 5
• KRXXYLCDFFDQFJ-UHFFFAOYSA-N 2-[1-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-3-methylpyrrolidin-3-yl]acetic acid Chemical compound FC=1C=CC(=C(C=1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1CC(CC1)(C)CC(=O)O)C(F)(F)F)C KRXXYLCDFFDQFJ-UHFFFAOYSA-N 0.000 claims description 5
• XAIJYBAKVAKOOP-UHFFFAOYSA-N 2-[1-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]-4-methylpiperidin-4-yl]acetic acid Chemical compound FC=1C=CC(=C(C=1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1CCC(CC1)(C)CC(=O)O)C(F)(F)F)C XAIJYBAKVAKOOP-UHFFFAOYSA-N 0.000 claims description 5
• WMJNOIVPJDPPFF-UHFFFAOYSA-N 2-[3-methyl-1-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-3-yl]acetic acid Chemical compound CC1(CN(CCC1)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)CC(=O)O WMJNOIVPJDPPFF-UHFFFAOYSA-N 0.000 claims description 5
• OUXGWQXTRLCAME-UHFFFAOYSA-N 2-[4-hydroxy-1-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-4-yl]-2-methylpropanoic acid Chemical compound OC1(CCN(CC1)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC=C1)C)(=O)=O)C(C(=O)O)(C)C OUXGWQXTRLCAME-UHFFFAOYSA-N 0.000 claims description 5
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• YTVFVUASTWIBRJ-SFHVURJKSA-N 3-[(3S)-1-[6-[[6-(2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]piperidin-3-yl]propanoic acid Chemical compound C1(=C(C=CC=C1)C1=C(C=CC(=N1)NS(=O)(=O)C1=CC=CC(=N1)N1C[C@@H](CCC1)CCC(=O)O)C(F)(F)F)C YTVFVUASTWIBRJ-SFHVURJKSA-N 0.000 claims description 5
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• AAJHZYBEUXAQKH-UHFFFAOYSA-N 3-[butyl-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)pyridin-2-yl]sulfamoyl]pyridin-2-yl]amino]propanoic acid Chemical compound C(CCC)N(CCC(=O)O)C1=NC(=CC=C1)S(NC1=NC(=C(C=C1)C(F)(F)F)C1=C(C=CC(=C1)F)C)(=O)=O AAJHZYBEUXAQKH-UHFFFAOYSA-N 0.000 claims description 5
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• 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 5
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