JP2007530550A - 異脂肪血症を治療するための化合物および方法 - Google Patents

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Publication number

JP2007530550A

JP2007530550A JP2007505054A JP2007505054A JP2007530550A JP 2007530550 A JP2007530550 A JP 2007530550A JP 2007505054 A JP2007505054 A JP 2007505054A JP 2007505054 A JP2007505054 A JP 2007505054A JP 2007530550 A JP2007530550 A JP 2007530550A

Authority

JP

Japan

Prior art keywords

trifluoromethyl

alkyl

ethyl

amino

dihydro

Prior art date

2004-03-26

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.)

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 225
• 238000000034 method Methods 0.000 title claims abstract description 104
• 208000032928 Dyslipidaemia Diseases 0.000 title claims abstract description 10
• 208000017170 Lipid metabolism disease Diseases 0.000 title abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
• -1 C 1 -C 6 alkyl Chemical group 0.000 claims description 191
• 239000000203 mixture Substances 0.000 claims description 109
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 77
• 125000003118 aryl group Chemical group 0.000 claims description 55
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 49
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 42
• 125000000623 heterocyclic group Chemical group 0.000 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 39
• 230000002829 reductive effect Effects 0.000 claims description 38
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 37
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 33
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 30
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 27
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 27
• 230000000694 effects Effects 0.000 claims description 26
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 23
• 239000012453 solvate Substances 0.000 claims description 23
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
• 239000002253 acid Substances 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 239000001257 hydrogen Substances 0.000 claims description 20
• 125000004043 oxo group Chemical group O=* 0.000 claims description 20
• 125000000217 alkyl group Chemical group 0.000 claims description 18
• 235000012000 cholesterol Nutrition 0.000 claims description 18
• 201000001320 Atherosclerosis Diseases 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 12
• 101000880514 Homo sapiens Cholesteryl ester transfer protein Proteins 0.000 claims description 11
• 238000008214 LDL Cholesterol Methods 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 241000124008 Mammalia Species 0.000 claims description 8
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 8
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
• 125000004104 aryloxy group Chemical group 0.000 claims description 7
• HZLBQACKQBXYOJ-UHFFFAOYSA-N propan-2-yl 2h-1,5-naphthyridine-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)C)CC=CC2=N1 HZLBQACKQBXYOJ-UHFFFAOYSA-N 0.000 claims description 7
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 6
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 6
• ZOGQIRTZEIKUSQ-UHFFFAOYSA-N C1CC2=C(C=CC=N2)N(C1C(F)(F)F)C(=O)OC3CCOC3 Chemical compound C1CC2=C(C=CC=N2)N(C1C(F)(F)F)C(=O)OC3CCOC3 ZOGQIRTZEIKUSQ-UHFFFAOYSA-N 0.000 claims description 6
• 108010028554 LDL Cholesterol Proteins 0.000 claims description 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 230000001575 pathological effect Effects 0.000 claims description 6
• VYLOCWWSRRXEAY-UHFFFAOYSA-N propan-2-yl 2-methyl-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)C)C(C)CCC2=N1 VYLOCWWSRRXEAY-UHFFFAOYSA-N 0.000 claims description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
• 239000001301 oxygen Substances 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• RBSLKDOJYBQTCO-UHFFFAOYSA-N propan-2-yl 4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(5,6,7,8-tetrahydroquinolin-3-yl)amino]-2,3-dimethyl-3,4,6,7,8,9-hexahydro-2h-benzo[g][1,5]naphthyridine-1-carboxylate Chemical compound C12=NC=3CCCCC=3C=C2N(C(=O)OC(C)C)C(C)C(C)C1N(C=1C=C2CCCCC2=NC=1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RBSLKDOJYBQTCO-UHFFFAOYSA-N 0.000 claims description 4
• 239000011593 sulfur Chemical group 0.000 claims description 4
• 229930192474 thiophene Natural products 0.000 claims description 4
• ILTMWUNJDKYAIT-KNQAVFIVSA-N (1-methylpiperidin-4-yl) (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OC1CCN(C)CC1)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ILTMWUNJDKYAIT-KNQAVFIVSA-N 0.000 claims description 3
• NNBXQRRUSRVBHP-QUCCMNQESA-N (3-methoxy-2,2-dimethyl-3-oxopropyl) (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OCC(C)(C)C(=O)OC)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NNBXQRRUSRVBHP-QUCCMNQESA-N 0.000 claims description 3
• GWPJCNACWLRZCK-AEFFLSMTSA-N 2-(2h-tetrazol-5-yl)ethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OCCC1=NNN=N1)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GWPJCNACWLRZCK-AEFFLSMTSA-N 0.000 claims description 3
• LYJNKBYQMZPMHT-QUCCMNQESA-N 2-(dimethylamino)ethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OCCN(C)C)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 LYJNKBYQMZPMHT-QUCCMNQESA-N 0.000 claims description 3
• CZEMWVHMWPXEIF-AEFFLSMTSA-N 2-hydroxyethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OCCO)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CZEMWVHMWPXEIF-AEFFLSMTSA-N 0.000 claims description 3
• ASNKHNLLYPGHQM-IRLDBZIGSA-N 2-morpholin-4-ylethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OCCN1CCOCC1)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ASNKHNLLYPGHQM-IRLDBZIGSA-N 0.000 claims description 3
• KULPFNDMMBOUEL-NOZRDPDXSA-N 2-phenylmethoxyethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OCCOCC=1C=CC=CC=1)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KULPFNDMMBOUEL-NOZRDPDXSA-N 0.000 claims description 3
• PHAPQTRQNMFLIZ-MJGOQNOKSA-N 3-[(2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carbonyl]oxy-2,2-dimethylpropanoic acid Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OCC(C)(C)C(O)=O)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PHAPQTRQNMFLIZ-MJGOQNOKSA-N 0.000 claims description 3
• HKIYBPBTPLEQTN-AEFFLSMTSA-N ethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@@H](CC)N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HKIYBPBTPLEQTN-AEFFLSMTSA-N 0.000 claims description 3
• WLAQGYCTEGMFOD-NQIIRXRSSA-N oxan-4-yl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OC1CCOCC1)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WLAQGYCTEGMFOD-NQIIRXRSSA-N 0.000 claims description 3
• FVMOZMLQLDXVNW-ICSRJNTNSA-N propan-2-yl (2S,4S)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-[2-(2-hydroxyethyl)tetrazol-5-yl]amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(CCO)N=C1N([C@H]1C[C@@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OC(C)C)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FVMOZMLQLDXVNW-ICSRJNTNSA-N 0.000 claims description 3
• FVMOZMLQLDXVNW-QUCCMNQESA-N propan-2-yl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-[2-(2-hydroxyethyl)tetrazol-5-yl]amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(CCO)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OC(C)C)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FVMOZMLQLDXVNW-QUCCMNQESA-N 0.000 claims description 3
• QLQICZLTQHFGRS-AZUAARDMSA-N propan-2-yl (2s,4r)-4-[[2-(2-aminoethyl)tetrazol-5-yl]-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(CCN)N=C1N([C@@H]1C[C@@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OC(C)C)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 QLQICZLTQHFGRS-AZUAARDMSA-N 0.000 claims description 3
• FVMOZMLQLDXVNW-AZUAARDMSA-N propan-2-yl (2s,4r)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-[2-(2-hydroxyethyl)tetrazol-5-yl]amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(CCO)N=C1N([C@@H]1C[C@@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OC(C)C)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FVMOZMLQLDXVNW-AZUAARDMSA-N 0.000 claims description 3
• FPQJBMBIIPSOBY-UHFFFAOYSA-N propan-2-yl 2-(fluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)C)C(CF)CCC2=N1 FPQJBMBIIPSOBY-UHFFFAOYSA-N 0.000 claims description 3
• KZPNHUVBHNWBAT-UHFFFAOYSA-N propan-2-yl 2-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)C)C(C(F)(F)F)CCC2=C1 KZPNHUVBHNWBAT-UHFFFAOYSA-N 0.000 claims description 3
• FWFBXCGTTOEINR-UHFFFAOYSA-N propan-2-yl 7-[acetyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-5-ethyl-6,7-dihydro-5h-thieno[3,2-b]pyridine-4-carboxylate Chemical compound C1=2SC=CC=2N(C(=O)OC(C)C)C(CC)CC1N(C(C)=O)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FWFBXCGTTOEINR-UHFFFAOYSA-N 0.000 claims description 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
• 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 2
• 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 2
• 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 2
• NLRNYHOHJCMPTI-MSOLQXFVSA-N CC[C@@H]1C[C@@H](C2=C(N1C(=O)OC(C)C)C=CC(=N2)C(F)(F)F)N=C3NNN(N3CC4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)C Chemical compound CC[C@@H]1C[C@@H](C2=C(N1C(=O)OC(C)C)C=CC(=N2)C(F)(F)F)N=C3NNN(N3CC4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)C NLRNYHOHJCMPTI-MSOLQXFVSA-N 0.000 claims description 2
• NUJGEWJYORDXMR-CTNGQTDRSA-N ethyl (2r,4s)-4-[[2-(2-aminoethyl)tetrazol-5-yl]-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-2-ethyl-6-methyl-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(CCN)N=C1N([C@H]1C[C@@H](CC)N(C2=CC=C(C)N=C21)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NUJGEWJYORDXMR-CTNGQTDRSA-N 0.000 claims description 2
• GBGXOZJGKVXCTJ-QUCCMNQESA-N ethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-methyl-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@@H](CC)N(C2=CC=C(C)N=C21)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GBGXOZJGKVXCTJ-QUCCMNQESA-N 0.000 claims description 2
• MOLCDSDOJLDXFF-CTNGQTDRSA-N ethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-[2-(2-hydroxyethyl)tetrazol-5-yl]amino]-2-ethyl-6-methyl-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(CCO)N=C1N([C@H]1C[C@@H](CC)N(C2=CC=C(C)N=C21)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 MOLCDSDOJLDXFF-CTNGQTDRSA-N 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• PSHMSKVXFVFRIA-QUCCMNQESA-N methyl (2r,4s)-4-[[2-(2-aminoethyl)tetrazol-5-yl]-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-2-ethyl-6-methyl-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(CCN)N=C1N([C@H]1C[C@H](N(C2=CC=C(C)N=C21)C(=O)OC)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PSHMSKVXFVFRIA-QUCCMNQESA-N 0.000 claims description 2
• WUKLOLBZWZYUHN-ACJLOTCBSA-N methyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2,6-dimethyl-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@@H](C)N(C2=CC=C(C)N=C21)C(=O)OC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WUKLOLBZWZYUHN-ACJLOTCBSA-N 0.000 claims description 2
• FJKXVDJUZWEPFR-MJGOQNOKSA-N methyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-2-ethyl-6-methyl-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(C)N=C21)C(=O)OC)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FJKXVDJUZWEPFR-MJGOQNOKSA-N 0.000 claims description 2
• HFHKRMLIAQPQNF-QUCCMNQESA-N methyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-[2-(2-hydroxyethyl)tetrazol-5-yl]amino]-2-ethyl-6-methyl-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(CCO)N=C1N([C@H]1C[C@H](N(C2=CC=C(C)N=C21)C(=O)OC)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HFHKRMLIAQPQNF-QUCCMNQESA-N 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• VHBLJIFFDINWGR-MJGOQNOKSA-N propan-2-yl (2r,4s)-2-ethyl-4-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]-6-(trifluoromethyl)-3,4-dihydro-2h-1,5-naphthyridine-1-carboxylate Chemical compound N1=NN(C)N=C1N([C@H]1C[C@H](N(C2=CC=C(N=C21)C(F)(F)F)C(=O)OC(C)C)CC)CC1=CC(F)=CC(C(F)(F)F)=C1 VHBLJIFFDINWGR-MJGOQNOKSA-N 0.000 claims description 2
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