AU2020223150A1 - Substituted amide compounds useful as farnesoid X receptor modulators - Google Patents
Substituted amide compounds useful as farnesoid X receptor modulators Download PDFInfo
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- AU2020223150A1 AU2020223150A1 AU2020223150A AU2020223150A AU2020223150A1 AU 2020223150 A1 AU2020223150 A1 AU 2020223150A1 AU 2020223150 A AU2020223150 A AU 2020223150A AU 2020223150 A AU2020223150 A AU 2020223150A AU 2020223150 A1 AU2020223150 A1 AU 2020223150A1
- Authority
- AU
- Australia
- Prior art keywords
- bicyclo
- methyl
- octan
- carboxamide
- oxadiazol
- 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.)
- Abandoned
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- -1 amide compounds Chemical class 0.000 title claims abstract description 178
- 102100038495 Bile acid receptor Human genes 0.000 title description 59
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 title description 59
- 150000001875 compounds Chemical class 0.000 claims abstract description 329
- 150000003839 salts Chemical class 0.000 claims abstract description 79
- 239000012453 solvate Substances 0.000 claims abstract description 55
- 125000000623 heterocyclic group Chemical group 0.000 claims description 98
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 69
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 65
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 64
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 62
- GUYWKLDYKANEIH-UHFFFAOYSA-N N-(3-chlorophenyl)-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound ClC=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F GUYWKLDYKANEIH-UHFFFAOYSA-N 0.000 claims description 59
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 54
- 229910052731 fluorine Inorganic materials 0.000 claims description 44
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 43
- 229910052801 chlorine Inorganic materials 0.000 claims description 43
- 208000035475 disorder Diseases 0.000 claims description 41
- AWXXNEOTLRMFKW-UHFFFAOYSA-N bicyclo[1.1.1]pentane-3-carboxamide Chemical compound C1C2CC1(C(=O)N)C2 AWXXNEOTLRMFKW-UHFFFAOYSA-N 0.000 claims description 40
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 37
- 125000005842 heteroatom Chemical group 0.000 claims description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 34
- 125000004043 oxo group Chemical group O=* 0.000 claims description 33
- 229910052717 sulfur Inorganic materials 0.000 claims description 31
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 28
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 27
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
- 125000004122 cyclic group Chemical group 0.000 claims description 25
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 25
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 206010016654 Fibrosis Diseases 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 230000004761 fibrosis Effects 0.000 claims description 20
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 239000004202 carbamide Substances 0.000 claims description 17
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 239000003937 drug carrier Substances 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 14
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 14
- 125000000335 thiazolyl group Chemical group 0.000 claims description 14
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 13
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 11
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 11
- 208000027866 inflammatory disease Diseases 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 9
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 9
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 9
- 210000004185 liver Anatomy 0.000 claims description 9
- XTQRSTWJSATPID-UHFFFAOYSA-N methyl 2-[3-[[4-[3-chloro-4-(dimethylamino)phenyl]-1-bicyclo[2.2.2]octanyl]methyl-(cyclohexanecarbonyl)amino]phenoxy]acetate Chemical compound ClC=1C=C(C=CC=1N(C)C)C12CCC(CC1)(CC2)CN(C(=O)C1CCCCC1)C=1C=C(OCC(=O)OC)C=CC=1 XTQRSTWJSATPID-UHFFFAOYSA-N 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 8
- UPZZWOPNWYPRHI-UHFFFAOYSA-N N-[[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]methyl]-N-[3-(4-ethoxyanilino)phenyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound C(C)(C)(C)C1=NOC(=N1)C12CCC(CC1)(CC2)CN(C(=O)C12CC(C1)(C2)F)C1=CC(=CC=C1)NC1=CC=C(C=C1)OCC UPZZWOPNWYPRHI-UHFFFAOYSA-N 0.000 claims description 8
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 8
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 8
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 8
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 6
- XJVCBQQIEWBUJL-UHFFFAOYSA-N 1,1-dioxothiane-4-carboxamide Chemical compound NC(=O)C1CCS(=O)(=O)CC1 XJVCBQQIEWBUJL-UHFFFAOYSA-N 0.000 claims description 6
- QQKZBEXAJYXJKN-UHFFFAOYSA-N 3-[cyclohexanecarbonyl-[[4-(3-methyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]methyl]amino]-N-(1,3-thiazol-2-yl)benzamide Chemical compound CC1=NOC(=N1)C12CCC(CC1)(CC2)CN(C(=O)C1CCCCC1)C=1C=C(C(=O)NC=2SC=CN=2)C=CC=1 QQKZBEXAJYXJKN-UHFFFAOYSA-N 0.000 claims description 6
- WEPJTJQNXINKFL-UHFFFAOYSA-N N-(3-bromophenyl)-3-fluoro-N-[[4-[5-(1-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]bicyclo[1.1.1]pentane-1-carboxamide Chemical compound BrC=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C1(CC1)F WEPJTJQNXINKFL-UHFFFAOYSA-N 0.000 claims description 6
- HSESCXOBDMFLHS-UHFFFAOYSA-N N-(3-bromophenyl)-3-fluoro-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]bicyclo[1.1.1]pentane-1-carboxamide Chemical compound BrC=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(F)(F)F HSESCXOBDMFLHS-UHFFFAOYSA-N 0.000 claims description 6
- BKKSLUIWLNOKBI-UHFFFAOYSA-N N-(3-bromophenyl)-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-2,2-difluorocyclopropane-1-carboxamide Chemical compound BrC=1C=C(C=CC=1)N(C(=O)C1C(C1)(F)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F BKKSLUIWLNOKBI-UHFFFAOYSA-N 0.000 claims description 6
- XLABGHDIGXUFAA-UHFFFAOYSA-N N-(3-bromophenyl)-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound BrC=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F XLABGHDIGXUFAA-UHFFFAOYSA-N 0.000 claims description 6
- BRXHBOBIAPOTNQ-UHFFFAOYSA-N N-(3-carbamoylphenyl)-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound C(N)(=O)C=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F BRXHBOBIAPOTNQ-UHFFFAOYSA-N 0.000 claims description 6
- FAGOBWQTGRNMAG-UHFFFAOYSA-N N-(3-cyanophenyl)-N-[1-[4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]ethyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)C(C)C12CCC(CC1)(CC2)C1=NC(=NO1)C1CC1 FAGOBWQTGRNMAG-UHFFFAOYSA-N 0.000 claims description 6
- CSKVOLQGSMAHCG-UHFFFAOYSA-N N-(3-cyanophenyl)-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F CSKVOLQGSMAHCG-UHFFFAOYSA-N 0.000 claims description 6
- DGSMVAFEVCAAAP-UHFFFAOYSA-N N-[[4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]methyl]-3,3-difluoro-N-[3-(methanesulfonamido)phenyl]cyclobutane-1-carboxamide Chemical compound C1(CC1)C1=NOC(=N1)C12CCC(CC1)(CC2)CN(C(=O)C1CC(C1)(F)F)C1=CC(=CC=C1)NS(=O)(=O)C DGSMVAFEVCAAAP-UHFFFAOYSA-N 0.000 claims description 6
- JDWOSRFIVRZSLS-UHFFFAOYSA-N N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-4,4-difluoro-N-[3-(trifluoromethyl)phenyl]cyclohexane-1-carboxamide Chemical compound FC(C)(F)C1=NC(=NO1)C12CCC(CC1)(CC2)CN(C(=O)C1CCC(CC1)(F)F)C1=CC(=CC=C1)C(F)(F)F JDWOSRFIVRZSLS-UHFFFAOYSA-N 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- SYARPIYWAUALII-UHFFFAOYSA-N methyl 3-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl-(3-fluorobicyclo[1.1.1]pentane-1-carbonyl)amino]benzoate Chemical compound FC(C)(F)C1=NC(=NO1)C12CCC(CC1)(CC2)CN(C(=O)C12CC(C1)(C2)F)C=1C=C(C(=O)OC)C=CC=1 SYARPIYWAUALII-UHFFFAOYSA-N 0.000 claims description 6
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- AOQSVRJIILIZGU-UHFFFAOYSA-N tert-butyl N-[3-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl-(3-fluorobicyclo[1.1.1]pentane-1-carbonyl)amino]phenyl]carbamate Chemical compound FC(C)(F)C1=NC(=NO1)C12CCC(CC1)(CC2)CN(C(=O)C12CC(C1)(C2)F)C=1C=C(C=CC=1)NC(OC(C)(C)C)=O AOQSVRJIILIZGU-UHFFFAOYSA-N 0.000 claims description 6
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims description 5
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 5
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 5
- SSQVBQNUNXHHHU-UHFFFAOYSA-N N-(3-bromo-4-chlorophenyl)-N-[[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound BrC=1C=C(C=CC=1Cl)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NC(=NO1)C(C)(C)C SSQVBQNUNXHHHU-UHFFFAOYSA-N 0.000 claims description 5
- SETUBMTYGIZFPQ-UHFFFAOYSA-N N-(3-bromophenyl)-N-[[4-[5-(1,1-difluoroethyl)pyridin-2-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound BrC=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NC=C(C=C1)C(C)(F)F SETUBMTYGIZFPQ-UHFFFAOYSA-N 0.000 claims description 5
- JQZCGAHDUXNWBR-UHFFFAOYSA-N N-(3-chlorophenyl)-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carboxamide Chemical compound ClC=1C=C(C=CC=1)N(C(=O)C1CC(C1)(C(F)(F)F)O)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F JQZCGAHDUXNWBR-UHFFFAOYSA-N 0.000 claims description 5
- TYTIADAOUUZZLV-UHFFFAOYSA-N N-(3-cyanophenyl)-N-[[4-[5-(1,1-difluoroethyl)pyridin-2-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound C(#N)C=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NC=C(C=C1)C(C)(F)F TYTIADAOUUZZLV-UHFFFAOYSA-N 0.000 claims description 5
- HYCIMQBQRCMVIR-UHFFFAOYSA-N N-[3-(cyclopropylsulfamoyl)phenyl]-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound C1(CC1)NS(=O)(=O)C=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F HYCIMQBQRCMVIR-UHFFFAOYSA-N 0.000 claims description 5
- DLIYGCIBPVXCTQ-UHFFFAOYSA-N N-[[4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]methyl]-N-(3-ethoxyphenyl)-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound C1(CC1)C1=NOC(=N1)C12CCC(CC1)(CC2)CN(C(=O)C12CC(C1)(C2)F)C1=CC(=CC=C1)OCC DLIYGCIBPVXCTQ-UHFFFAOYSA-N 0.000 claims description 5
- GTVIUYHWPUILKR-UHFFFAOYSA-N N-[[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]methyl]-N-(3-cyanophenyl)-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound C(C)(C)(C)C1=NOC(=N1)C12CCC(CC1)(CC2)CN(C(=O)C12CC(C1)(C2)F)C1=CC(=CC=C1)C#N GTVIUYHWPUILKR-UHFFFAOYSA-N 0.000 claims description 5
- FQKWWKLKDXQUTJ-UHFFFAOYSA-N N-[[4-(5-cyclopropyl-2-methylpyrazol-3-yl)-1-bicyclo[2.2.2]octanyl]methyl]-4,4-difluoro-N-(3-methylsulfonylphenyl)cyclohexane-1-carboxamide Chemical compound C1(CC1)C1=NN(C(=C1)C12CCC(CC1)(CC2)CN(C(=O)C1CCC(CC1)(F)F)C1=CC(=CC=C1)S(=O)(=O)C)C FQKWWKLKDXQUTJ-UHFFFAOYSA-N 0.000 claims description 5
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 5
- FTTWQXXYSUXMNN-UHFFFAOYSA-N methyl 2-[3-[cyclohexanecarbonyl-[[4-[4-(dimethylamino)phenyl]-1-bicyclo[2.2.2]octanyl]methyl]amino]phenoxy]acetate Chemical compound CN(C1=CC=C(C=C1)C12CCC(CC1)(CC2)CN(C(=O)C1CCCCC1)C=1C=C(OCC(=O)OC)C=CC=1)C FTTWQXXYSUXMNN-UHFFFAOYSA-N 0.000 claims description 5
- 230000001575 pathological effect Effects 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 208000010157 sclerosing cholangitis Diseases 0.000 claims description 5
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 4
- LZNCBDSBQDTSTA-UHFFFAOYSA-N 1-(3-cyanophenyl)-1-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-(3-hydroxy-2,2-dimethylpropyl)urea Chemical compound C(#N)C=1C=C(C=CC=1)N(C(=O)NCC(CO)(C)C)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F LZNCBDSBQDTSTA-UHFFFAOYSA-N 0.000 claims description 4
- OIZJYDDBJRWBNQ-UHFFFAOYSA-N 1-(3-cyanophenyl)-1-[[4-[5-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-(3-hydroxy-2,2-dimethylpropyl)urea Chemical compound C(#N)C=1C=C(C=CC=1)N(C(=O)NCC(CO)(C)C)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(C)F OIZJYDDBJRWBNQ-UHFFFAOYSA-N 0.000 claims description 4
- PPMCBRCXGQGTNZ-UHFFFAOYSA-N 3-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl-(3-fluorobicyclo[1.1.1]pentane-1-carbonyl)amino]benzoic acid Chemical compound FC(C)(F)C1=NC(=NO1)C12CCC(CC1)(CC2)CN(C(=O)C12CC(C1)(C2)F)C=1C=C(C(=O)O)C=CC=1 PPMCBRCXGQGTNZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- CCUGRWBRFQYSMJ-UHFFFAOYSA-N N-(3-bromophenyl)-N-[[4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.1]heptanyl]methyl]-3-fluorobicyclo[1.1.1]pentane-1-carboxamide Chemical compound BrC=1C=C(C=CC=1)N(C(=O)C12CC(C1)(C2)F)CC12CCC(CC1)(C2)C1=NC(=NO1)C(C)(C)C CCUGRWBRFQYSMJ-UHFFFAOYSA-N 0.000 claims description 4
- ZGPKMLAQGBLPEW-UHFFFAOYSA-N N-(3-chlorophenyl)-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-4,4-difluorocyclohexane-1-carboxamide Chemical compound ClC=1C=C(C=CC=1)N(C(=O)C1CCC(CC1)(F)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F ZGPKMLAQGBLPEW-UHFFFAOYSA-N 0.000 claims description 4
- SNOUTJYVYQVEOF-UHFFFAOYSA-N N-(3-cyano-5-fluorophenyl)-N-[[4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-bicyclo[2.2.2]octanyl]methyl]-3,3-difluorocyclobutane-1-carboxamide Chemical compound C(#N)C=1C=C(C=C(C=1)F)N(C(=O)C1CC(C1)(F)F)CC12CCC(CC1)(CC2)C1=NC(=NO1)C1CC1 SNOUTJYVYQVEOF-UHFFFAOYSA-N 0.000 claims description 4
- REUZZPDLQFIISE-UHFFFAOYSA-N N-(3-cyano-5-fluorophenyl)-N-[[4-[5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3,3-difluorocyclobutane-1-carboxamide Chemical compound C(#N)C=1C=C(C=C(C=1)F)N(C(=O)C1CC(C1)(F)F)CC12CCC(CC1)(CC2)C1=NOC(=N1)C(C)(F)F REUZZPDLQFIISE-UHFFFAOYSA-N 0.000 claims description 4
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Classifications
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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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
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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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
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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
- C07D213/04—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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D401/02—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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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2020
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- 2020-02-14 WO PCT/US2020/018211 patent/WO2020168149A1/en not_active Ceased
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- 2020-02-14 MX MX2021009424A patent/MX2021009424A/es unknown
- 2020-02-14 EA EA202192275A patent/EA202192275A1/ru unknown
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| IL285510A (en) | 2021-09-30 |
| CN113727973A (zh) | 2021-11-30 |
| KR20210129684A (ko) | 2021-10-28 |
| CN113727973B (zh) | 2025-08-29 |
| BR112021015688A2 (pt) | 2021-10-26 |
| US20220081430A1 (en) | 2022-03-17 |
| JP7550777B2 (ja) | 2024-09-13 |
| MX2021009424A (es) | 2021-09-10 |
| JP2022519771A (ja) | 2022-03-24 |
| WO2020168149A1 (en) | 2020-08-20 |
| CA3129851A1 (en) | 2020-08-20 |
| EP3924333A1 (en) | 2021-12-22 |
| US12319676B2 (en) | 2025-06-03 |
| SG11202108794RA (en) | 2021-09-29 |
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