SI9600183A - Therapeutic amides - Google Patents
Therapeutic amides Download PDFInfo
- Publication number
- SI9600183A SI9600183A SI9600183A SI9600183A SI9600183A SI 9600183 A SI9600183 A SI 9600183A SI 9600183 A SI9600183 A SI 9600183A SI 9600183 A SI9600183 A SI 9600183A SI 9600183 A SI9600183 A SI 9600183A
- Authority
- SI
- Slovenia
- Prior art keywords
- trifluoromethyl
- biphenyl
- carboxylic acid
- amide
- tetrahydroisoquinolin
- Prior art date
Links
- 150000001408 amides Chemical class 0.000 title claims description 18
- 230000001225 therapeutic effect Effects 0.000 title description 2
- -1 cyano, nitro, oxo, thioxo, aminosulfonyl Chemical group 0.000 claims abstract description 212
- 150000001875 compounds Chemical class 0.000 claims abstract description 139
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 28
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims abstract description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 125000001424 substituent group Chemical group 0.000 claims abstract description 16
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 14
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 13
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims abstract description 12
- 125000002252 acyl group Chemical group 0.000 claims abstract description 12
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 9
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 7
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 7
- 229910052717 sulfur Chemical group 0.000 claims abstract description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 7
- 229920002554 vinyl polymer Polymers 0.000 claims abstract description 7
- 229920001774 Perfluoroether Polymers 0.000 claims abstract description 6
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 5
- 125000006554 (C4-C8) cycloalkenyl group Chemical group 0.000 claims abstract description 5
- 239000011593 sulfur Chemical group 0.000 claims abstract description 5
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000005110 aryl thio group Chemical group 0.000 claims abstract description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 125000004465 cycloalkenyloxy group Chemical group 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 125000005592 polycycloalkyl group Polymers 0.000 claims abstract description 4
- 125000006413 ring segment Chemical group 0.000 claims abstract description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 7
- IQOMYCGTGFGDFN-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IQOMYCGTGFGDFN-UHFFFAOYSA-N 0.000 claims description 70
- 239000002253 acid Substances 0.000 claims description 61
- 150000003254 radicals Chemical class 0.000 claims description 23
- SYBKBPXOVQYFFA-UHFFFAOYSA-N 2-[2-(hydroxymethyl)-5-nitrophenyl]ethanol Chemical compound OCCC1=CC([N+]([O-])=O)=CC=C1CO SYBKBPXOVQYFFA-UHFFFAOYSA-N 0.000 claims description 17
- 125000005647 linker group Chemical group 0.000 claims description 13
- 229940124530 sulfonamide Drugs 0.000 claims description 9
- 150000003456 sulfonamides Chemical class 0.000 claims description 9
- 150000001735 carboxylic acids Chemical class 0.000 claims description 8
- AKMALXRXYAFPLL-UHFFFAOYSA-N tert-butyl 6-nitro-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 AKMALXRXYAFPLL-UHFFFAOYSA-N 0.000 claims description 8
- 150000007513 acids Chemical class 0.000 claims description 7
- OLOIFCYZWOTWRO-UHFFFAOYSA-N tert-butyl 6-amino-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound NC1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 OLOIFCYZWOTWRO-UHFFFAOYSA-N 0.000 claims description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000001555 benzenes Chemical class 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- POXYSHFMRRORKX-UHFFFAOYSA-N 2-[5-amino-2-(hydroxymethyl)phenyl]ethanol Chemical compound NC1=CC=C(CO)C(CCO)=C1 POXYSHFMRRORKX-UHFFFAOYSA-N 0.000 claims description 4
- ZOPPPZYLBABVSW-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1 ZOPPPZYLBABVSW-UHFFFAOYSA-N 0.000 claims description 4
- FUFSAQUQRGODRR-UHFFFAOYSA-N 2-phenyl-6-(trifluoromethyl)benzoic acid Chemical compound C1=CC=C(C(F)(F)F)C(C(=O)O)=C1C1=CC=CC=C1 FUFSAQUQRGODRR-UHFFFAOYSA-N 0.000 claims description 4
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- XOYOWXXIKWPXFC-UHFFFAOYSA-N n-(1,2,3,4-tetrahydroisoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CNCC2)C2=C1 XOYOWXXIKWPXFC-UHFFFAOYSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- IPBZICXEEPVWTK-UHFFFAOYSA-N n-[1-(2-phenylacetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(NCC2)C(=O)CC=3C=CC=CC=3)C2=C1 IPBZICXEEPVWTK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 150000003556 thioamides Chemical class 0.000 claims description 3
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- UALJVGZBTOOZQQ-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-n-[2-[(2,6,6-trimethylcyclohex-2-en-1-yl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]benzamide Chemical compound CC1=CCCC(C)(C)C1CN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 UALJVGZBTOOZQQ-UHFFFAOYSA-N 0.000 claims description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 2
- OBEAPZCDNGOTJV-UHFFFAOYSA-N 2-benzyl-3,4-dihydro-1h-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=CC=CC=C1 OBEAPZCDNGOTJV-UHFFFAOYSA-N 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
- 239000003524 antilipemic agent Substances 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 239000004202 carbamide Substances 0.000 claims description 2
- KTKJCGKOCTXFRX-UHFFFAOYSA-N tert-butyl 6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical group C=1C=C2CN(C(=O)OC(C)(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 KTKJCGKOCTXFRX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 6
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea group Chemical group NC(=S)N UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims 2
- VBLDQJIRPICNBW-UHFFFAOYSA-N (6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-pyridin-2-ylmethanone Chemical compound C1CC2=CC(N)=CC=C2CN1C(=O)C1=CC=CC=N1 VBLDQJIRPICNBW-UHFFFAOYSA-N 0.000 claims 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 125000006681 (C2-C10) alkylene group Chemical group 0.000 claims 1
- FTSVTCPUMUXYJS-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical group C1=C=C[C]2CNCCC2=C1 FTSVTCPUMUXYJS-UHFFFAOYSA-N 0.000 claims 1
- OVAFWEXNFPWMCA-UHFFFAOYSA-N 1-(6-amino-1,2,3,4-tetrahydroisoquinolin-1-yl)-2-phenoxyethanone Chemical compound N1CCC2=CC(N)=CC=C2C1C(=O)COC1=CC=CC=C1 OVAFWEXNFPWMCA-UHFFFAOYSA-N 0.000 claims 1
- IWAGGDFROAISJT-UHFFFAOYSA-N 1h-isoquinoline-2-carboxylic acid Chemical class C1=CC=C2C=CN(C(=O)O)CC2=C1 IWAGGDFROAISJT-UHFFFAOYSA-N 0.000 claims 1
- KCVKPKPNJUSQCH-UHFFFAOYSA-N 2-(1,3-thiazol-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-amine 2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound NC1=CC=C(CN(CC2=NC=CS2)CC2)C2=C1.OC(C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O KCVKPKPNJUSQCH-UHFFFAOYSA-N 0.000 claims 1
- UYBDRPVWEDIDFT-UHFFFAOYSA-N 2-(1H-1,2,4-triazol-5-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-amine 2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical group NC1=CC=C(CN(CC2=NNC=N2)CC2)C2=C1.OC(C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O UYBDRPVWEDIDFT-UHFFFAOYSA-N 0.000 claims 1
- VIHZDKCJRQAKLT-UHFFFAOYSA-N 2-(1H-imidazol-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=NC=CN1 VIHZDKCJRQAKLT-UHFFFAOYSA-N 0.000 claims 1
- DGNMALJXEGQNKL-UHFFFAOYSA-N 2-(1h-1,2,4-triazol-5-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=NC=NN1 DGNMALJXEGQNKL-UHFFFAOYSA-N 0.000 claims 1
- CUKAVTVGWFENTO-UHFFFAOYSA-N 2-(pyridin-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=CC=CC=N1 CUKAVTVGWFENTO-UHFFFAOYSA-N 0.000 claims 1
- KLLFTSTVDHKVEI-UHFFFAOYSA-N 2-[2-(trifluoromethoxy)phenyl]sulfonyl-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1S(=O)(=O)C1=CC=CC=C1OC(F)(F)F KLLFTSTVDHKVEI-UHFFFAOYSA-N 0.000 claims 1
- IPDRRTURNBKLIH-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IPDRRTURNBKLIH-UHFFFAOYSA-N 0.000 claims 1
- FPFSHYODIAZPGR-UHFFFAOYSA-N 2-phenyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)-5-(trifluoromethyl)benzamide Chemical compound C1NCCC2=CC(=CC=C12)NC(=O)C=1C(=CC=C(C1)C(F)(F)F)C1=CC=CC=C1 FPFSHYODIAZPGR-UHFFFAOYSA-N 0.000 claims 1
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims 1
- DMTUABMWMZTNQO-UHFFFAOYSA-N CCCC(=S)C1C2=C(CCN1)C=C(C=C2)C3=CC=CC(=C3C(=O)N)C4=CC=C(C=C4)C(F)(F)F Chemical compound CCCC(=S)C1C2=C(CCN1)C=C(C=C2)C3=CC=CC(=C3C(=O)N)C4=CC=C(C=C4)C(F)(F)F DMTUABMWMZTNQO-UHFFFAOYSA-N 0.000 claims 1
- KTRMLDWHWDLLNL-UHFFFAOYSA-N COCC(=O)C1C2=C(CCN1)C=C(C=C2)C3=CC=CC(=C3C(=O)N)C4=CC=C(C=C4)C(F)(F)F Chemical compound COCC(=O)C1C2=C(CCN1)C=C(C=C2)C3=CC=CC(=C3C(=O)N)C4=CC=C(C=C4)C(F)(F)F KTRMLDWHWDLLNL-UHFFFAOYSA-N 0.000 claims 1
- AVEJPRXCBCHUEY-UHFFFAOYSA-N N-(2-propan-2-ylsulfonyl-3,4-dihydro-1H-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(S(=O)(=O)C(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 AVEJPRXCBCHUEY-UHFFFAOYSA-N 0.000 claims 1
- PZDVADQHNQIGEE-UHFFFAOYSA-N NC1=CC=C2CN(C(=O)CCC)CCC2=C1.OC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 Chemical compound NC1=CC=C2CN(C(=O)CCC)CCC2=C1.OC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 PZDVADQHNQIGEE-UHFFFAOYSA-N 0.000 claims 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims 1
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 claims 1
- WXIVOQCTQSVGAQ-UHFFFAOYSA-N n-[2-(2-thiophen-2-ylacetyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)CC=3SC=CC=3)C2=C1 WXIVOQCTQSVGAQ-UHFFFAOYSA-N 0.000 claims 1
- MANDBIMAUNFYAR-UHFFFAOYSA-N n-[2-(cyclopropylcarbamothioyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=S)NC3CC3)C2=C1 MANDBIMAUNFYAR-UHFFFAOYSA-N 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 43
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 abstract description 18
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 abstract description 18
- 230000028327 secretion Effects 0.000 abstract description 11
- 239000000203 mixture Substances 0.000 abstract description 10
- 208000008589 Obesity Diseases 0.000 abstract description 8
- 235000020824 obesity Nutrition 0.000 abstract description 8
- 201000010099 disease Diseases 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 239000003112 inhibitor Substances 0.000 abstract description 7
- 210000002966 serum Anatomy 0.000 abstract description 5
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 4
- 125000006664 (C1-C3) perfluoroalkyl group Chemical group 0.000 abstract description 3
- 101710095342 Apolipoprotein B Proteins 0.000 abstract description 3
- 102100040202 Apolipoprotein B-100 Human genes 0.000 abstract description 3
- 150000002632 lipids Chemical class 0.000 abstract description 3
- 230000002265 prevention Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- 239000002904 solvent Substances 0.000 description 52
- 239000000243 solution Substances 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 43
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 42
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- 229910052799 carbon Inorganic materials 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 229920000642 polymer Polymers 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- 239000002502 liposome Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 7
- 229930006000 Sucrose Natural products 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000005720 sucrose Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 229940086542 triethylamine Drugs 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 206010003210 Arteriosclerosis Diseases 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 5
- CKXXWBQEZGLFMV-UHFFFAOYSA-N 2-(carboxymethyl)-4-nitrobenzoic acid Chemical compound OC(=O)CC1=CC([N+]([O-])=O)=CC=C1C(O)=O CKXXWBQEZGLFMV-UHFFFAOYSA-N 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- OUZGPBWVRKFMLS-UHFFFAOYSA-N 6-nitro-1,2,3,4-tetrahydroisoquinoline Chemical compound C1NCCC2=CC([N+](=O)[O-])=CC=C21 OUZGPBWVRKFMLS-UHFFFAOYSA-N 0.000 description 5
- QSYIKBIUQZLICL-UHFFFAOYSA-N 6-phenyl-6-(trifluoromethyl)cyclohexa-2,4-diene-1-carboxylic acid Chemical compound FC(C1(C(C=CC=C1)C(=O)O)C1=CC=CC=C1)(F)F QSYIKBIUQZLICL-UHFFFAOYSA-N 0.000 description 5
- 102000018616 Apolipoproteins B Human genes 0.000 description 5
- 108010027006 Apolipoproteins B Proteins 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- 206010033645 Pancreatitis Diseases 0.000 description 5
- 238000013019 agitation Methods 0.000 description 5
- 125000001931 aliphatic group Chemical group 0.000 description 5
- 150000001412 amines Chemical group 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 125000001183 hydrocarbyl group Chemical group 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 5
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 5
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- SAAFIVJVSQVSSW-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-6-amine Chemical compound C1NCCC2=CC(N)=CC=C21 SAAFIVJVSQVSSW-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 208000035150 Hypercholesterolemia Diseases 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000001540 azides Chemical class 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 description 4
- 235000013877 carbamide Nutrition 0.000 description 4
- 125000002837 carbocyclic group Chemical group 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 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 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 208000006575 hypertriglyceridemia Diseases 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- OYODEQFZAJVROF-UHFFFAOYSA-N 7-bromo-1,2,3,4-tetrahydroisoquinoline Chemical compound C1CNCC2=CC(Br)=CC=C21 OYODEQFZAJVROF-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000003228 microsomal effect Effects 0.000 description 3
- MVBSTLOVKYCSCX-UHFFFAOYSA-N n-[2-(4-bromophenyl)ethyl]formamide Chemical compound BrC1=CC=C(CCNC=O)C=C1 MVBSTLOVKYCSCX-UHFFFAOYSA-N 0.000 description 3
- GYPJVCGKIBMXFE-UHFFFAOYSA-N n-[3-(2-hydroxyethyl)-4-(hydroxymethyl)phenyl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=C(CO)C(CCO)=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 GYPJVCGKIBMXFE-UHFFFAOYSA-N 0.000 description 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- 150000003585 thioureas Chemical class 0.000 description 3
- 150000003626 triacylglycerols Chemical class 0.000 description 3
- 150000003672 ureas Chemical class 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- OUMKBAHMPRLISR-UHFFFAOYSA-N 1-phenyl-4-(trifluoromethyl)benzene Chemical group C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1 OUMKBAHMPRLISR-UHFFFAOYSA-N 0.000 description 2
- VFDVBQMLLPCXNP-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoyl chloride Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(Cl)=O VFDVBQMLLPCXNP-UHFFFAOYSA-N 0.000 description 2
- OABDJQNESRYMSZ-UHFFFAOYSA-N 2-propan-2-ylsulfonyl-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound NC1=CC=C2CN(S(=O)(=O)C(C)C)CCC2=C1 OABDJQNESRYMSZ-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- PTMIMUGQDHCIBP-UHFFFAOYSA-N 3-[5-[[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1H-isoquinolin-2-yl]methyl]furan-2-yl]propanoic acid Chemical compound FC(C1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)NC=1C=C2CCN(CC2=CC1)CC1=CC=C(O1)CCC(=O)O)(F)F PTMIMUGQDHCIBP-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- SOHKDNJLUQRYNG-UHFFFAOYSA-N 6-nitro-4h-isochromene-1,3-dione Chemical compound O=C1OC(=O)CC2=CC([N+](=O)[O-])=CC=C21 SOHKDNJLUQRYNG-UHFFFAOYSA-N 0.000 description 2
- TZRGFYNFHUFUAW-UHFFFAOYSA-N 7-bromo-3,4-dihydroisoquinoline;hydrochloride Chemical compound Cl.C1CN=CC2=CC(Br)=CC=C21 TZRGFYNFHUFUAW-UHFFFAOYSA-N 0.000 description 2
- MLIZUKAIRKGUIM-UHFFFAOYSA-N 7-bromo-6-nitro-1,2,3,4-tetrahydroisoquinoline Chemical compound C1CNCC2=C1C=C([N+](=O)[O-])C(Br)=C2 MLIZUKAIRKGUIM-UHFFFAOYSA-N 0.000 description 2
- QAYNSPOKTRVZRC-UHFFFAOYSA-N 99-60-5 Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1Cl QAYNSPOKTRVZRC-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- WIVNKEJCDIBTPC-UHFFFAOYSA-N N-[3-(2-hydroxyethyl)-4-(hydroxymethyl)phenyl]-2-phenyl-5-(trifluoromethyl)benzamide Chemical compound OCCC=1C=C(C=CC1CO)NC(=O)C=1C(=CC=C(C1)C(F)(F)F)C1=CC=CC=C1 WIVNKEJCDIBTPC-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 244000000231 Sesamum indicum Species 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- KIPWHSSTNMNUDS-UHFFFAOYSA-N [N].C1NCCC2=CC=CC=C12 Chemical compound [N].C1NCCC2=CC=CC=C12 KIPWHSSTNMNUDS-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 2
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- NONOKGVFTBWRLD-UHFFFAOYSA-N isocyanatosulfanylimino(oxo)methane Chemical compound O=C=NSN=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- ITJYVAJPJUJZOO-UHFFFAOYSA-N n-(2-benzyl-3,4-dihydro-1h-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2C=CC=CC=2)CC2)C2=C1 ITJYVAJPJUJZOO-UHFFFAOYSA-N 0.000 description 2
- LBBXOYBEGXAARL-UHFFFAOYSA-N n-[2-(1,3-thiazol-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2SC=CN=2)CC2)C2=C1 LBBXOYBEGXAARL-UHFFFAOYSA-N 0.000 description 2
- DINIOHTXSFVUIM-UHFFFAOYSA-N n-[2-(1-acetylpyrrolidine-2-carbonyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CC(=O)N1CCCC1C(=O)N1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 DINIOHTXSFVUIM-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 2
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- RVAPXPOTRYDTJS-UHFFFAOYSA-N tert-butyl 7-bromo-6-nitro-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound [O-][N+](=O)C1=C(Br)C=C2CN(C(=O)OC(C)(C)C)CCC2=C1 RVAPXPOTRYDTJS-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- CZHWILSCHVMQLC-UHFFFAOYSA-N (6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-(4-heptylphenyl)methanone Chemical compound C1=CC(CCCCCCC)=CC=C1C(=O)N1CC2=CC=C(N)C=C2CC1 CZHWILSCHVMQLC-UHFFFAOYSA-N 0.000 description 1
- STEHKYHXCWFWKJ-UHFFFAOYSA-N (6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-(oxolan-3-yl)methanone Chemical compound C1CC2=CC(N)=CC=C2CN1C(=O)C1CCOC1 STEHKYHXCWFWKJ-UHFFFAOYSA-N 0.000 description 1
- OOONAKRWOAMPQX-UHFFFAOYSA-N (6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-quinoxalin-2-ylmethanone Chemical compound C1=CC=CC2=NC(C(=O)N3CC4=CC=C(C=C4CC3)N)=CN=C21 OOONAKRWOAMPQX-UHFFFAOYSA-N 0.000 description 1
- VSBQCADCZCVLKS-UHFFFAOYSA-N (6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-thiophen-2-ylmethanone Chemical compound C1CC2=CC(N)=CC=C2CN1C(=O)C1=CC=CS1 VSBQCADCZCVLKS-UHFFFAOYSA-N 0.000 description 1
- FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
- QIXSYRICKPSRKY-UHFFFAOYSA-N 1-(6-amino-1,2,3,4-tetrahydroisoquinolin-1-yl)-2-methoxyethanone Chemical compound NC1=CC=C2C(C(=O)COC)NCCC2=C1 QIXSYRICKPSRKY-UHFFFAOYSA-N 0.000 description 1
- VWDHVRYTZFLPSM-UHFFFAOYSA-N 1-(6-amino-1,2,3,4-tetrahydroisoquinolin-1-yl)butane-1-thione Chemical compound NC1=CC=C2C(C(=S)CCC)NCCC2=C1 VWDHVRYTZFLPSM-UHFFFAOYSA-N 0.000 description 1
- FIUSRODEPLPOIZ-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-2-chloropropan-1-one Chemical compound NC1=CC=C2CN(C(=O)C(Cl)C)CCC2=C1 FIUSRODEPLPOIZ-UHFFFAOYSA-N 0.000 description 1
- GGFIFHHZGZLGHT-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-2-ethylhexan-1-one Chemical compound NC1=CC=C2CN(C(=O)C(CC)CCCC)CCC2=C1 GGFIFHHZGZLGHT-UHFFFAOYSA-N 0.000 description 1
- NXIIWIGSKWQEFS-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-2-phenylbutan-1-one Chemical compound C1CC2=CC(N)=CC=C2CN1C(=O)C(CC)C1=CC=CC=C1 NXIIWIGSKWQEFS-UHFFFAOYSA-N 0.000 description 1
- ZAYJBTHCUWPLJS-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-3-chlorobutan-1-one Chemical compound NC1=CC=C2CN(C(=O)CC(Cl)C)CCC2=C1 ZAYJBTHCUWPLJS-UHFFFAOYSA-N 0.000 description 1
- VEVIJVLDCORHKR-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-3-methylbutan-1-one Chemical compound NC1=CC=C2CN(C(=O)CC(C)C)CCC2=C1 VEVIJVLDCORHKR-UHFFFAOYSA-N 0.000 description 1
- ZCOZEURYTNIDNZ-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)but-3-en-1-one Chemical compound C1N(C(=O)CC=C)CCC2=CC(N)=CC=C21 ZCOZEURYTNIDNZ-UHFFFAOYSA-N 0.000 description 1
- CVCBPXVFNLZMQN-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)hexan-1-one Chemical compound NC1=CC=C2CN(C(=O)CCCCC)CCC2=C1 CVCBPXVFNLZMQN-UHFFFAOYSA-N 0.000 description 1
- FJXPNYCSOVSNOS-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)octan-1-one Chemical compound NC1=CC=C2CN(C(=O)CCCCCCC)CCC2=C1 FJXPNYCSOVSNOS-UHFFFAOYSA-N 0.000 description 1
- GVPWWZPHRUCYNA-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)pentan-1-one Chemical compound NC1=CC=C2CN(C(=O)CCCC)CCC2=C1 GVPWWZPHRUCYNA-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000980 1H-indol-3-ylmethyl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[*])C2=C1[H] 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- PHYFQTYBJUILEZ-MMZUPMTFSA-N 2,3-bis[[(Z)-octadec-9-enoyl]oxy]propyl (Z)-(114C)octadec-9-enoate Chemical compound O=[14C](CCCCCCC\C=C/CCCCCCCC)OCC(COC(CCCCCCC\C=C/CCCCCCCC)=O)OC(CCCCCCC\C=C/CCCCCCCC)=O PHYFQTYBJUILEZ-MMZUPMTFSA-N 0.000 description 1
- LPWHGVILSZJCQD-UHFFFAOYSA-N 2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-4-nitrobenzoic acid Chemical compound COC(=O)C(C(=O)OC)C1=CC([N+]([O-])=O)=CC=C1C(O)=O LPWHGVILSZJCQD-UHFFFAOYSA-N 0.000 description 1
- HWQMHUAOUPWPSA-UHFFFAOYSA-N 2-(1,3-thiazol-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=NC=CS1 HWQMHUAOUPWPSA-UHFFFAOYSA-N 0.000 description 1
- CVQPSNSCPLYESH-UHFFFAOYSA-N 2-(1H-pyrrol-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=CC=CN1 CVQPSNSCPLYESH-UHFFFAOYSA-N 0.000 description 1
- QKVGEXXFRLFGGK-UHFFFAOYSA-N 2-(2-carboxy-5-nitrophenyl)propanedioic acid Chemical compound OC(=O)C(C(O)=O)C1=CC([N+]([O-])=O)=CC=C1C(O)=O QKVGEXXFRLFGGK-UHFFFAOYSA-N 0.000 description 1
- YCOLMBKFSOPIQC-UHFFFAOYSA-N 2-(3-chloropropylsulfonyl)-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1N(S(=O)(=O)CCCCl)CCC2=CC(N)=CC=C21 YCOLMBKFSOPIQC-UHFFFAOYSA-N 0.000 description 1
- ZSZCXAOQVBEPME-UHFFFAOYSA-N 2-(4-bromophenyl)ethanamine Chemical compound NCCC1=CC=C(Br)C=C1 ZSZCXAOQVBEPME-UHFFFAOYSA-N 0.000 description 1
- IUWPMHYAMOUYKQ-UHFFFAOYSA-N 2-(4-bromophenyl)ethylazanium;bromide Chemical compound [Br-].[NH3+]CCC1=CC=C(Br)C=C1 IUWPMHYAMOUYKQ-UHFFFAOYSA-N 0.000 description 1
- YYXZEYXSGKTRMA-UHFFFAOYSA-N 2-(furan-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=CC=CO1 YYXZEYXSGKTRMA-UHFFFAOYSA-N 0.000 description 1
- VZMYVCOELJDSHT-UHFFFAOYSA-N 2-(pyridin-3-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=CC=CN=C1 VZMYVCOELJDSHT-UHFFFAOYSA-N 0.000 description 1
- UIRWYVIIZWONBE-UHFFFAOYSA-N 2-[(2,5-dimethoxyoxolan-3-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound COC1OC(OC)CC1CN1CC2=CC=C(N)C=C2CC1 UIRWYVIIZWONBE-UHFFFAOYSA-N 0.000 description 1
- GRZPWSALAPYYKG-UHFFFAOYSA-N 2-[(2-chlorophenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=CC=CC=C1Cl GRZPWSALAPYYKG-UHFFFAOYSA-N 0.000 description 1
- BDRAAGYUGCBAPR-UHFFFAOYSA-N 2-[(3-chlorophenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=CC=CC(Cl)=C1 BDRAAGYUGCBAPR-UHFFFAOYSA-N 0.000 description 1
- UMIGGMKLUUIZGZ-UHFFFAOYSA-N 2-[(3-phenoxyphenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC(C=1)=CC=CC=1OC1=CC=CC=C1 UMIGGMKLUUIZGZ-UHFFFAOYSA-N 0.000 description 1
- FSELGGHSTGCUJM-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1=CC(OC)=CC=C1CN1CC2=CC=C(N)C=C2CC1 FSELGGHSTGCUJM-UHFFFAOYSA-N 0.000 description 1
- AQWDWLVKVGMRPM-UHFFFAOYSA-N 2-[2-(2,2,5,7-tetramethyl-1-oxo-3H-indene-4-carbonyl)-3,4-dihydro-1H-isoquinolin-6-yl]-6-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CC1(C(C=2C(=CC(=C(C2C1)C(=O)N1CC2=CC=C(C=C2CC1)C1=C(C(=CC=C1)C1=CC=C(C=C1)C(F)(F)F)C(=O)N)C)C)=O)C AQWDWLVKVGMRPM-UHFFFAOYSA-N 0.000 description 1
- UVLTWQHRRYKMNM-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-N-[2-[[3-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-1H-isoquinolin-6-yl]benzamide Chemical compound FC(C=1C=C(CN2CC3=CC=C(C=C3CC2)NC(=O)C=2C(=CC=CC=2)C2=CC=C(C=C2)C(F)(F)F)C=CC=1)(F)F UVLTWQHRRYKMNM-UHFFFAOYSA-N 0.000 description 1
- GMUIEQXTGZEBIP-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-n-[2-[[2-(trifluoromethyl)phenyl]methyl]-3,4-dihydro-1h-isoquinolin-6-yl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2C(=CC=CC=2)C(F)(F)F)CC2)C2=C1 GMUIEQXTGZEBIP-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 1
- PWHRVVMNFQGSJQ-UHFFFAOYSA-N 2-methyl-3,4-dihydro-1h-isoquinolin-6-amine Chemical compound NC1=CC=C2CN(C)CCC2=C1 PWHRVVMNFQGSJQ-UHFFFAOYSA-N 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- SZQVEGOXJYTLLB-UHFFFAOYSA-N 3-cyclopentylpropanoyl chloride Chemical compound ClC(=O)CCC1CCCC1 SZQVEGOXJYTLLB-UHFFFAOYSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- ZBCKPYWNLXIONW-UHFFFAOYSA-N 6-amino-3,4-dihydro-1h-isoquinoline-2-carboxylic acid Chemical compound C1N(C(O)=O)CCC2=CC(N)=CC=C21 ZBCKPYWNLXIONW-UHFFFAOYSA-N 0.000 description 1
- BXSOJVFGOJGNNF-UHFFFAOYSA-N 6-amino-N-cyclopropyl-3,4-dihydro-1H-isoquinoline-2-carbothioamide Chemical compound C1CC2=CC(N)=CC=C2CN1C(=S)NC1CC1 BXSOJVFGOJGNNF-UHFFFAOYSA-N 0.000 description 1
- YQQLGLRTMLGKDQ-UHFFFAOYSA-N 7-bromo-3,4-dihydroisoquinoline Chemical compound C1CN=CC2=CC(Br)=CC=C21 YQQLGLRTMLGKDQ-UHFFFAOYSA-N 0.000 description 1
- GGZZISOUXJHYOY-UHFFFAOYSA-N 8-amino-4-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C(N)=CC=CC2=C1O GGZZISOUXJHYOY-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- ZUDPJMYKHHDBPH-UHFFFAOYSA-N C1=CC([N+](=O)[O-])=CC=C1CC(=O)N1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 Chemical compound C1=CC([N+](=O)[O-])=CC=C1CC(=O)N1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 ZUDPJMYKHHDBPH-UHFFFAOYSA-N 0.000 description 1
- HWRZQJZOFZFEJZ-UHFFFAOYSA-N C1CC=CC(C1)CN2CCC3=C(C2)C=CC(=C3)NC(=O)C4=CC=CC=C4C5=CC=C(C=C5)C(F)(F)F Chemical compound C1CC=CC(C1)CN2CCC3=C(C2)C=CC(=C3)NC(=O)C4=CC=CC=C4C5=CC=C(C=C5)C(F)(F)F HWRZQJZOFZFEJZ-UHFFFAOYSA-N 0.000 description 1
- QDLHDHBAFMCJMJ-UHFFFAOYSA-N C=1C=C2CN(C(=O)C(CC)CC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 Chemical compound C=1C=C2CN(C(=O)C(CC)CC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 QDLHDHBAFMCJMJ-UHFFFAOYSA-N 0.000 description 1
- QMRRIESUBOWEAR-UHFFFAOYSA-N CC1(C2CC=C(C1C2)CN3CCC4=C(C3)C=CC(=C4)C5=CC=CC(=C5C(=O)N)C6=CC=C(C=C6)C(F)(F)F)C Chemical compound CC1(C2CC=C(C1C2)CN3CCC4=C(C3)C=CC(=C4)C5=CC=CC(=C5C(=O)N)C6=CC=C(C=C6)C(F)(F)F)C QMRRIESUBOWEAR-UHFFFAOYSA-N 0.000 description 1
- JKQLUSMWKMDNCE-UHFFFAOYSA-N CC1=CC=CC(CN2CC3=CC=C(NC(=O)C=4C(=CC=CC=4)C=4C=CC(=CC=4)C(F)(F)F)C=C3CC2)=C1 Chemical compound CC1=CC=CC(CN2CC3=CC=C(NC(=O)C=4C(=CC=CC=4)C=4C=CC(=CC=4)C(F)(F)F)C=C3CC2)=C1 JKQLUSMWKMDNCE-UHFFFAOYSA-N 0.000 description 1
- UXAYSXRZUIIRFA-UHFFFAOYSA-N CN1C(CN(CCC2=C3)CC2=CC=C3N)=NC=C1.FC(C(C=C1)=CC=C1C1=CC=CC=C1)(F)F Chemical compound CN1C(CN(CCC2=C3)CC2=CC=C3N)=NC=C1.FC(C(C=C1)=CC=C1C1=CC=CC=C1)(F)F UXAYSXRZUIIRFA-UHFFFAOYSA-N 0.000 description 1
- MRUKPMHVFANHQO-UHFFFAOYSA-N CN1C=CC=C1CN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 Chemical compound CN1C=CC=C1CN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 MRUKPMHVFANHQO-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical group OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101100514827 Homo sapiens MTTP gene Proteins 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 235000014435 Mentha Nutrition 0.000 description 1
- 241001072983 Mentha Species 0.000 description 1
- 229920001367 Merrifield resin Polymers 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- TYKVAWADSNLZLW-UHFFFAOYSA-N N-(2-benzoyl-3,4-dihydro-1H-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)C=3C=CC=CC=3)C2=C1 TYKVAWADSNLZLW-UHFFFAOYSA-N 0.000 description 1
- ZIIWPSGAXXKFRW-UHFFFAOYSA-N N-(2-butylsulfonyl-3,4-dihydro-1H-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(S(=O)(=O)CCCC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 ZIIWPSGAXXKFRW-UHFFFAOYSA-N 0.000 description 1
- WTCSXIRNDJRXHM-UHFFFAOYSA-N N-(2-octadecanoyl-3,4-dihydro-1H-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(C(=O)CCCCCCCCCCCCCCCCC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 WTCSXIRNDJRXHM-UHFFFAOYSA-N 0.000 description 1
- BILNHISZPWOZMX-UHFFFAOYSA-N N-[2-(2,2-dimethylpropanoyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(C(=O)C(C)(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 BILNHISZPWOZMX-UHFFFAOYSA-N 0.000 description 1
- ZYAKCLHJPZENJZ-UHFFFAOYSA-N N-[2-(2,2-diphenylacetyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)C(C=3C=CC=CC=3)C=3C=CC=CC=3)C2=C1 ZYAKCLHJPZENJZ-UHFFFAOYSA-N 0.000 description 1
- UZSCWOPBJYRBET-UHFFFAOYSA-N N-[2-(2-naphthalen-2-ylacetyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)CC=3C=C4C=CC=CC4=CC=3)C2=C1 UZSCWOPBJYRBET-UHFFFAOYSA-N 0.000 description 1
- IAWDGXBUZKUGRD-UHFFFAOYSA-N N-[2-(3-methyl-4-oxopentanoyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(C(=O)CC(C)C(C)=O)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IAWDGXBUZKUGRD-UHFFFAOYSA-N 0.000 description 1
- SPQJHHYOVFNZQV-UHFFFAOYSA-N N-[2-(3-phenylpropanoyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)CCC=3C=CC=CC=3)C2=C1 SPQJHHYOVFNZQV-UHFFFAOYSA-N 0.000 description 1
- AFJRQRGZXPYQCN-UHFFFAOYSA-N N-[2-(cyclohexylmethyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2CCCCC2)CC2)C2=C1 AFJRQRGZXPYQCN-UHFFFAOYSA-N 0.000 description 1
- AYCPLCPTLHKLTD-UHFFFAOYSA-N N-[2-(naphthalen-1-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2C3=CC=CC=C3C=CC=2)CC2)C2=C1 AYCPLCPTLHKLTD-UHFFFAOYSA-N 0.000 description 1
- HTQLPGBGOMIIOQ-UHFFFAOYSA-N N-[2-[(2,4-dichlorophenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2C(=CC(Cl)=CC=2)Cl)CC2)C2=C1 HTQLPGBGOMIIOQ-UHFFFAOYSA-N 0.000 description 1
- QKXYQEXAFZBLHF-UHFFFAOYSA-N N-[2-[(2-tert-butylsulfanylphenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CC(C)(C)SC1=CC=CC=C1CN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 QKXYQEXAFZBLHF-UHFFFAOYSA-N 0.000 description 1
- BUQTWFBCPGGISJ-UHFFFAOYSA-N N-[2-[(3-hydroxyphenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound OC1=CC=CC(CN2CC3=CC=C(NC(=O)C=4C(=CC=CC=4)C=4C=CC(=CC=4)C(F)(F)F)C=C3CC2)=C1 BUQTWFBCPGGISJ-UHFFFAOYSA-N 0.000 description 1
- LJRVLYRLOXXSSK-UHFFFAOYSA-N N-[2-[(3-methoxyphenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound COC1=CC=CC(CN2CC3=CC=C(NC(=O)C=4C(=CC=CC=4)C=4C=CC(=CC=4)C(F)(F)F)C=C3CC2)=C1 LJRVLYRLOXXSSK-UHFFFAOYSA-N 0.000 description 1
- VPOJGGQCXXOJFD-UHFFFAOYSA-N N-[2-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CN1C=NC=C1CN1CCC2=C(C1)C=CC(NC(=O)C1=C(C=CC=C1)C1=CC=C(C=C1)C(F)(F)F)=C2 VPOJGGQCXXOJFD-UHFFFAOYSA-N 0.000 description 1
- DJUZVMDRWXUYFJ-UHFFFAOYSA-N N-[2-[(3-nitrophenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound [O-][N+](=O)C1=CC=CC(CN2CC3=CC=C(NC(=O)C=4C(=CC=CC=4)C=4C=CC(=CC=4)C(F)(F)F)C=C3CC2)=C1 DJUZVMDRWXUYFJ-UHFFFAOYSA-N 0.000 description 1
- DIAFXJDEYRFAHD-UHFFFAOYSA-N N-[2-[(4-chlorophenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2C=CC(Cl)=CC=2)CC2)C2=C1 DIAFXJDEYRFAHD-UHFFFAOYSA-N 0.000 description 1
- CFYBBRGIRQATGK-UHFFFAOYSA-N N-[2-[(4-methoxynaphthalen-1-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound COC1=CC=C(C2=CC=CC=C12)CN1CC2=CC=C(C=C2CC1)NC(=O)C=1C(=CC=CC=1)C1=CC=C(C=C1)C(F)(F)F CFYBBRGIRQATGK-UHFFFAOYSA-N 0.000 description 1
- ZTOYLCKLJXFUPX-UHFFFAOYSA-N N-[2-[(4-methylsulfanylphenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(SC)=CC=C1CN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 ZTOYLCKLJXFUPX-UHFFFAOYSA-N 0.000 description 1
- RSOAEBWSFHEJAK-UHFFFAOYSA-N N-[2-[2-(3-methoxyphenyl)acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound COC=1C=C(C=CC=1)CC(=O)N1CC2=CC=C(C=C2CC1)NC(=O)C=1C(=CC=CC=1)C1=CC=C(C=C1)C(F)(F)F RSOAEBWSFHEJAK-UHFFFAOYSA-N 0.000 description 1
- ZJVMHRAFXYAOPU-UHFFFAOYSA-N N-[2-[2-(trifluoromethoxy)phenyl]sulfonyl-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound FC(F)(F)OC1=CC=CC=C1S(=O)(=O)N1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 ZJVMHRAFXYAOPU-UHFFFAOYSA-N 0.000 description 1
- UIRGUXDGXKGTLT-UHFFFAOYSA-N NC1=CC=C(CNCC2)C2=C1.OC(C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O Chemical compound NC1=CC=C(CNCC2)C2=C1.OC(C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O UIRGUXDGXKGTLT-UHFFFAOYSA-N 0.000 description 1
- JWSNZIPYTJJYFW-UHFFFAOYSA-N NC1=CC=C2CN(C(=O)CCC)CCC2=C1 Chemical compound NC1=CC=C2CN(C(=O)CCC)CCC2=C1 JWSNZIPYTJJYFW-UHFFFAOYSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- BYLKFSDQZQJZAC-UHFFFAOYSA-N S(C)(=O)(=O)O.C(CC(O)(C(=O)O)CC(=O)O)(=O)O.CS(=O)(=O)O Chemical compound S(C)(=O)(=O)O.C(CC(O)(C(=O)O)CC(=O)O)(=O)O.CS(=O)(=O)O BYLKFSDQZQJZAC-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 description 1
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 1
- JJSCUXAFAJEQGB-MRVPVSSYSA-N [(1r)-1-isocyanatoethyl]benzene Chemical compound O=C=N[C@H](C)C1=CC=CC=C1 JJSCUXAFAJEQGB-MRVPVSSYSA-N 0.000 description 1
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Chemical group CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000001118 alkylidene group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 229940096699 bile acid sequestrants Drugs 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- OYPRJOBELJOOCE-KUYOKYOWSA-N calcium-49 Chemical compound [49Ca] OYPRJOBELJOOCE-KUYOKYOWSA-N 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001717 carbocyclic compounds Chemical class 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- DDKMFOUTRRODRE-UHFFFAOYSA-N chloromethanone Chemical compound Cl[C]=O DDKMFOUTRRODRE-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003113 cycloheptyloxy group Chemical group C1(CCCCCC1)O* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
- PXJJSXABGXMUSU-UHFFFAOYSA-N disulfur dichloride Chemical compound ClSSCl PXJJSXABGXMUSU-UHFFFAOYSA-N 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- MEKPCPGDJSKKHO-UHFFFAOYSA-N ethyl 2-[[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinolin-2-yl]methyl]cyclopropane-1-carboxylate Chemical compound CCOC(=O)C1CC1CN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 MEKPCPGDJSKKHO-UHFFFAOYSA-N 0.000 description 1
- JJOYCHKVKWDMEA-UHFFFAOYSA-N ethyl cyclohexanecarboxylate Chemical compound CCOC(=O)C1CCCCC1 JJOYCHKVKWDMEA-UHFFFAOYSA-N 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- QQROCCOOMLPJBD-UHFFFAOYSA-N isocyanatosulfanylcyclopropane Chemical compound O=C=NSC1CC1 QQROCCOOMLPJBD-UHFFFAOYSA-N 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- QPVJWWSAHGIHIG-UHFFFAOYSA-N methyl 2-[[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinolin-2-yl]sulfonyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1S(=O)(=O)N1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 QPVJWWSAHGIHIG-UHFFFAOYSA-N 0.000 description 1
- NRBZOEVTKHVTJE-UHFFFAOYSA-N methyl 4-oxo-4-[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinolin-2-yl]butanoate Chemical compound C=1C=C2CN(C(=O)CCC(=O)OC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 NRBZOEVTKHVTJE-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 235000014569 mints Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- RONNIDMEEXKTTP-UHFFFAOYSA-N n-(2-butanoyl-3,4-dihydro-1h-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(C(=O)CCC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 RONNIDMEEXKTTP-UHFFFAOYSA-N 0.000 description 1
- DEGHKTUSGCWFIM-UHFFFAOYSA-N n-(2-naphthalen-1-ylsulfonyl-3,4-dihydro-1h-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)S(=O)(=O)C=3C4=CC=CC=C4C=CC=3)C2=C1 DEGHKTUSGCWFIM-UHFFFAOYSA-N 0.000 description 1
- BIIALSBNYVHETG-UHFFFAOYSA-N n-[1-(2-cyanoacetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(NCC2)C(=O)CC#N)C2=C1 BIIALSBNYVHETG-UHFFFAOYSA-N 0.000 description 1
- JRINTFZAXWCVIK-UHFFFAOYSA-N n-[1-(2-phenoxyacetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(NCC2)C(=O)COC=3C=CC=CC=3)C2=C1 JRINTFZAXWCVIK-UHFFFAOYSA-N 0.000 description 1
- XJNSHVDKPFLXCT-UHFFFAOYSA-N n-[1-(2-phenylethanethioyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(NCC2)C(=S)CC=3C=CC=CC=3)C2=C1 XJNSHVDKPFLXCT-UHFFFAOYSA-N 0.000 description 1
- NOMJLQUJDQTDKX-UHFFFAOYSA-N n-[1-(3-phenylpropanethioyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(NCC2)C(=S)CCC=3C=CC=CC=3)C2=C1 NOMJLQUJDQTDKX-UHFFFAOYSA-N 0.000 description 1
- QOXGFOIPVYGKLZ-UHFFFAOYSA-N n-[2-(1h-imidazol-5-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2N=CNC=2)CC2)C2=C1 QOXGFOIPVYGKLZ-UHFFFAOYSA-N 0.000 description 1
- KEDZZOLFYJSFTQ-UHFFFAOYSA-N n-[2-(1h-pyrrol-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2NC=CC=2)CC2)C2=C1 KEDZZOLFYJSFTQ-UHFFFAOYSA-N 0.000 description 1
- FJBJEWUBQGYKNR-UHFFFAOYSA-N n-[2-(pyridin-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2N=CC=CC=2)CC2)C2=C1 FJBJEWUBQGYKNR-UHFFFAOYSA-N 0.000 description 1
- AATXUBKUICHKRX-UHFFFAOYSA-N n-[2-(pyridine-2-carbonyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)C=3N=CC=CC=3)C2=C1 AATXUBKUICHKRX-UHFFFAOYSA-N 0.000 description 1
- DRLCIQLMMFMQGH-UHFFFAOYSA-N n-[2-(thiophen-2-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2SC=CC=2)CC2)C2=C1 DRLCIQLMMFMQGH-UHFFFAOYSA-N 0.000 description 1
- FIUFQLNDOBULAY-UHFFFAOYSA-N n-[2-[(2-methoxynaphthalen-1-yl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound COC1=CC=C2C=CC=CC2=C1CN(CC1=CC=2)CCC1=CC=2NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 FIUFQLNDOBULAY-UHFFFAOYSA-N 0.000 description 1
- OHJCOUAHLJDICA-UHFFFAOYSA-N n-[2-[(3-fluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound FC1=CC=CC(CN2CC3=CC=C(NC(=O)C=4C(=CC=CC=4)C=4C=CC(=CC=4)C(F)(F)F)C=C3CC2)=C1 OHJCOUAHLJDICA-UHFFFAOYSA-N 0.000 description 1
- DSZBWAKLPVSMBG-UHFFFAOYSA-N n-[2-[(4-phenoxyphenyl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2C=CC(OC=3C=CC=CC=3)=CC=2)CC2)C2=C1 DSZBWAKLPVSMBG-UHFFFAOYSA-N 0.000 description 1
- HRDPRWDJSXCNAI-UHFFFAOYSA-N n-[2-[(6-bromopyridin-2-yl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC=2N=C(Br)C=CC=2)CC2)C2=C1 HRDPRWDJSXCNAI-UHFFFAOYSA-N 0.000 description 1
- KWTFUNJOOXYQMP-UHFFFAOYSA-N n-[2-[(6-methylpyridin-2-yl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CC1=CC=CC(CN2CC3=CC=C(NC(=O)C=4C(=CC=CC=4)C=4C=CC(=CC=4)C(F)(F)F)C=C3CC2)=N1 KWTFUNJOOXYQMP-UHFFFAOYSA-N 0.000 description 1
- AVRMEGVKEFENOL-UHFFFAOYSA-N n-benzyl-3,4-dihydro-1h-isoquinoline-2-carboxamide Chemical compound C1CC2=CC=CC=C2CN1C(=O)NCC1=CC=CC=C1 AVRMEGVKEFENOL-UHFFFAOYSA-N 0.000 description 1
- BUKMYSHUZXKWAX-UHFFFAOYSA-N n-hexyl-3,4-dihydro-1h-isoquinoline-2-carboxamide Chemical compound C1=CC=C2CN(C(=O)NCCCCCC)CCC2=C1 BUKMYSHUZXKWAX-UHFFFAOYSA-N 0.000 description 1
- DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- 125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- 125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229940081066 picolinic acid Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N sec-butylidene Natural products CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000004059 squalene synthase inhibitor Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- ITVJREJRWLZBTR-UHFFFAOYSA-N tert-butyl 2-[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carbonyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1C(=O)N1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 ITVJREJRWLZBTR-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 150000003566 thiocarboxylic acids Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 229940117972 triolein Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
- C07D401/02—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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
-
- 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
- C07D401/02—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
- C07D401/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/02—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
- C07D409/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D413/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/06—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 linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IB1995/000448 WO1996040640A1 (en) | 1995-06-07 | 1995-06-07 | BIPHENYL-2-CARBOXYLIC ACID-TETRAHYDRO-ISOQUINOLIN-6-YL AMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND/OR APOLIPOPROTEIN B (Apo B) SECRETION |
CA002223574A CA2223574C (en) | 1995-06-07 | 1995-06-07 | Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein b (apo b) secretion |
HU9601566A HUP9601566A3 (en) | 1995-06-07 | 1996-06-06 | Therapeutic tetrahydro-isoquinolin derivatives, their intermediates and pharmaceutical compositions containing the active component |
Publications (1)
Publication Number | Publication Date |
---|---|
SI9600183A true SI9600183A (en) | 1997-04-30 |
Family
ID=89994037
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SI9600183A SI9600183A (en) | 1995-06-07 | 1996-06-06 | Therapeutic amides |
Country Status (14)
Country | Link |
---|---|
EP (1) | EP0832069B1 (fi) |
AP (1) | AP9600804A0 (fi) |
BR (1) | BR9602628A (fi) |
CZ (1) | CZ289249B6 (fi) |
FI (1) | FI974440A (fi) |
HR (1) | HRP960270A2 (fi) |
HU (1) | HUP9601566A3 (fi) |
IL (1) | IL118484A (fi) |
LV (1) | LV11615B (fi) |
NZ (1) | NZ286733A (fi) |
PL (1) | PL314636A1 (fi) |
SG (1) | SG44952A1 (fi) |
SI (1) | SI9600183A (fi) |
WO (1) | WO1996040640A1 (fi) |
Families Citing this family (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5739135A (en) * | 1993-09-03 | 1998-04-14 | Bristol-Myers Squibb Company | Inhibitors of microsomal triglyceride transfer protein and method |
PL328094A1 (en) * | 1996-01-16 | 1999-01-04 | Bristol Myers Squibb Co | Conformingly restricted aromatic inhibitors triglycerides carrying chromosome protein and method of obtaining such inhibitors |
WO1997041111A1 (en) * | 1996-04-30 | 1997-11-06 | Pfizer Inc. | Processes and intermediates for preparing 4'-trifluoromethylbiphenyl-2-carboxylic acid [2-(2h-[1,2,4]triazol-3-ylmethyl)-1,2,3,4-tetrahydro-isoquinolin-6-yl]-amide |
US5827875A (en) * | 1996-05-10 | 1998-10-27 | Bristol-Myers Squibb Company | Inhibitors of microsomal triglyceride transfer protein and method |
US5885983A (en) * | 1996-05-10 | 1999-03-23 | Bristol-Myers Squibb Company | Inhibitors of microsomal triglyceride transfer protein and method |
TW438796B (en) * | 1996-05-15 | 2001-06-07 | Hoffmann La Roche | 2,4-diaminopyrimidine derivatives, the manufacture process thereof, and the antibiotically-active pharmaceutical composition containing the same |
US5883109A (en) * | 1996-07-24 | 1999-03-16 | Bristol-Myers Squibb Company | Method for lowering serum lipid levels employing an MTP inhibitor in combination with another cholesterol lowering drug |
WO1998023593A1 (en) * | 1996-11-27 | 1998-06-04 | Pfizer Inc. | Apo b-secretion/mtp inhibitory amides |
US5760246A (en) | 1996-12-17 | 1998-06-02 | Biller; Scott A. | Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method |
CN1252792A (zh) * | 1997-04-18 | 2000-05-10 | 辉瑞大药厂 | 制备4'-三氟甲基-联苯基-2-羧酸(1,2,3,4-四氢-异喹啉-6-基)酰胺的方法和中间体 |
GB9708119D0 (en) * | 1997-04-22 | 1997-06-11 | Glaxo Group Ltd | Chemical compounds |
US5968950A (en) * | 1997-06-23 | 1999-10-19 | Pfizer Inc | Apo B-secretion/MTP inhibitor hydrochloride salt |
EP1085846A2 (en) | 1998-06-08 | 2001-03-28 | Advanced Medicine, Inc. | Multibinding inhibitors of microsomal triglyceride transferase protein |
US6197798B1 (en) | 1998-07-21 | 2001-03-06 | Novartis Ag | Amino-benzocycloalkane derivatives |
CO5090829A1 (es) * | 1998-07-21 | 2001-10-30 | Novartis Ag | Compuestos organicos de la formula i, utiles como inhibido res de la proteina de transferencia de triglicerido microso mal y de la secrecion de la apolipoproteina b. |
GB9826412D0 (en) | 1998-12-03 | 1999-01-27 | Glaxo Group Ltd | Chemical compounds |
WO2001005767A1 (en) * | 1999-07-20 | 2001-01-25 | Novartis Ag | Organic compounds |
CA2324801A1 (en) * | 1999-11-10 | 2001-05-10 | Andrew Gordon Swick | Use of apo b secretion/mtp inhibitors and anti-obesity agents |
IL139450A0 (en) * | 1999-11-10 | 2001-11-25 | Pfizer Prod Inc | Methods of administering apo b-secretion/mtp inhibitors |
CA2324800A1 (en) * | 1999-11-10 | 2001-05-10 | Mary Anne Hickman | Use of apo b secretion/mtp inhibitors |
CO5271688A1 (es) * | 1999-11-10 | 2003-04-30 | Pfizer Prod Inc | Uso de inhibidor de secrecion de apoliproteinas b y/o de proteina de transferencia de trigliceridos microsmales |
AU2001262185A1 (en) * | 2000-04-10 | 2001-10-23 | Novartis Ag | Substituted (hetero)aryl carboxamide derivatives as microsomal triglyceride transfer protein (mtp) and apolipoprotein b (apo b) secretion |
GB0013383D0 (en) * | 2000-06-01 | 2000-07-26 | Glaxo Group Ltd | Therapeutic benzamide derivatives |
GB0013346D0 (en) * | 2000-06-01 | 2000-07-26 | Glaxo Group Ltd | Therapeutic benzamide derivatives |
DE10033337A1 (de) * | 2000-07-08 | 2002-01-17 | Boehringer Ingelheim Pharma | Biphenylcarbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
WO2002014277A1 (fr) * | 2000-08-10 | 2002-02-21 | Tanabe Seiyaku Co., Ltd. | Composes de biphenylcarboxamidoisoindoline, procedes de preparation de ceux-ci et produits intermediaires destines a la synthese de ceux-ci |
AU2001277727A1 (en) * | 2000-08-10 | 2002-02-25 | Tanabe Seiyaku Co., Ltd. | Benzoylaminoisoindoline compounds, processes for the preparation of the same andintermediates for the synthesis thereof |
JO2654B1 (en) | 2000-09-04 | 2012-06-17 | شركة جانسين فارماسوتيكا ان. في | Multiple aryl caroxa amides are useful as lipid - lowering agents |
EP1326835A1 (en) * | 2000-10-05 | 2003-07-16 | Fujisawa Pharmaceutical Co., Ltd. | Benzamide compounds as apo b secretion inhibitors |
JO2409B1 (en) | 2000-11-21 | 2007-06-17 | شركة جانسين فارماسوتيكا ان. في | Second-phenyl carboxy amides are useful as lipid-lowering agents |
JO2390B1 (en) * | 2001-04-06 | 2007-06-17 | شركة جانسين فارماسوتيكا ان. في | Diphenylcarboxamides act as lipid-lowering agents |
US20040157866A1 (en) * | 2001-04-30 | 2004-08-12 | Hisashi Takasugi | Amide compounds |
CN1522246B (zh) * | 2001-06-28 | 2010-04-21 | 辉瑞产品公司 | 三酰胺取代的吲哚、苯并呋喃及苯并噻吩 |
US20050038035A1 (en) * | 2001-11-28 | 2005-02-17 | Hisashi Takasugi | Heterocyclic amide compounds as apolipoprotein b inhibitors |
GB0129013D0 (en) * | 2001-12-04 | 2002-01-23 | Glaxo Group Ltd | Compounds |
GB0129015D0 (en) * | 2001-12-04 | 2002-01-23 | Glaxo Group Ltd | Compounds |
EP2033953A1 (en) * | 2002-02-15 | 2009-03-11 | Glaxo Group Limited | Vanilloid receptor modulators |
NZ531890A (en) | 2002-02-28 | 2006-02-24 | Japan Tobacco Inc | Ester compound and medicinal use thereof |
WO2004039795A2 (en) * | 2002-10-29 | 2004-05-13 | Fujisawa Pharmaceutical Co., Ltd. | Amide compounds for the treatment of hyperlipidemia |
CN1826121B (zh) * | 2003-07-23 | 2013-05-29 | 幸讬制药公司 | 苯基与吡啶基衍生物用于制备调控钙离子释放活化钙离子通道的药物的用途 |
EP1669345A4 (en) | 2003-08-29 | 2008-02-20 | Japan Tobacco Inc | ESTER DERIVATIVE AND MEDICAL USE THEREOF |
GB2406856B (en) * | 2003-10-07 | 2005-10-19 | Renovis Inc | Amide compounds as ion channel ligands and uses thereof |
GB2413129A (en) * | 2003-10-07 | 2005-10-19 | Renovis Inc | Aromatic amide compounds as ion channel ligands and uses thereof |
EP1716137A1 (en) | 2004-02-04 | 2006-11-02 | Pfizer Products Incorporated | Substituted quinoline compounds |
KR20060129082A (ko) | 2004-03-05 | 2006-12-14 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 부작용을 최소화하면서 과지질혈증 및 과콜레스테롤혈증과연관된 질환 또는 질병의 치료 방법 |
US8101774B2 (en) | 2004-10-18 | 2012-01-24 | Japan Tobacco Inc. | Ester derivatives and medicinal use thereof |
JP2006249022A (ja) | 2005-03-11 | 2006-09-21 | Sumitomo Chemical Co Ltd | 4−(2−メチルフェニル)ベンゾトリフルオライドの製造方法 |
MX2007013133A (es) | 2005-04-19 | 2008-03-14 | Surface Logix Inc | Inhibidores de la proteina microsomal de transferencia de trigliceridos de la secrecion de apo-b. |
US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
DE102005062987A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Propiolsäureamide und ihre Verwendung zur Herstellung von Arzneimitteln |
US8383660B2 (en) | 2006-03-10 | 2013-02-26 | Pfizer Inc. | Dibenzyl amine compounds and derivatives |
US7919506B2 (en) | 2006-03-10 | 2011-04-05 | Pfizer Inc. | Dibenzyl amine compounds and derivatives |
DK2046787T3 (da) | 2006-08-01 | 2011-07-18 | Glaxo Group Ltd | Pyrazolo[3,4-B]pyridin-forbindelser, og deres anvendelse som PDE4-inhibitorer |
JO2653B1 (en) | 2006-10-24 | 2012-06-17 | شركة جانسين فارماسوتيكا ان. في | Tetrahydroflavin 1-carboxylic acid substituted with pyridine or pyrazine inhibit MTB |
CN101528671B (zh) | 2006-10-24 | 2013-03-13 | 詹森药业有限公司 | 抑制mtp的四氢-萘-1-羧酸衍生物 |
JP5498168B2 (ja) | 2006-12-01 | 2014-05-21 | ブリストル−マイヤーズ スクイブ カンパニー | アテローム性動脈硬化および循環器疾患の治療のためのcetp阻害剤としてのn−((3−ベンジル)−2,2−(ビス−フェニル)−プロパン−1−アミン誘導体 |
EP2986599A1 (en) | 2013-04-17 | 2016-02-24 | Pfizer Inc. | N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases |
WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
BR112021013807A2 (pt) | 2019-01-18 | 2021-11-30 | Astrazeneca Ab | Inibidores de pcsk9 e seus métodos de uso |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4022900A (en) * | 1970-09-09 | 1977-05-10 | Marion Laboratories, Inc. | Compositions containing 1,2,3,4-tetrahydroisoquinolines used as hypotensive agents |
CA1248536A (en) * | 1982-09-10 | 1989-01-10 | Wellcome Foundation Limited (The) | Benzoil acid derivatives |
US5595872A (en) * | 1992-03-06 | 1997-01-21 | Bristol-Myers Squibb Company | Nucleic acids encoding microsomal trigyceride transfer protein |
IL110172A (en) * | 1993-07-22 | 2001-10-31 | Lilly Co Eli | Bicycle compounds and pharmaceuticals containing them |
-
1995
- 1995-06-07 EP EP95918722A patent/EP0832069B1/en not_active Expired - Lifetime
- 1995-06-07 WO PCT/IB1995/000448 patent/WO1996040640A1/en active IP Right Grant
-
1996
- 1996-05-09 AP APAP/P/1996/000804A patent/AP9600804A0/en unknown
- 1996-05-30 IL IL11848496A patent/IL118484A/en not_active IP Right Cessation
- 1996-06-04 BR BR9602628A patent/BR9602628A/pt not_active Application Discontinuation
- 1996-06-05 PL PL96314636A patent/PL314636A1/xx unknown
- 1996-06-05 NZ NZ286733A patent/NZ286733A/en unknown
- 1996-06-05 SG SG1996009974A patent/SG44952A1/en unknown
- 1996-06-06 HR HRPCT/IB95/00448A patent/HRP960270A2/hr not_active Application Discontinuation
- 1996-06-06 SI SI9600183A patent/SI9600183A/sl not_active IP Right Cessation
- 1996-06-06 CZ CZ19961644A patent/CZ289249B6/cs not_active IP Right Cessation
- 1996-06-06 HU HU9601566A patent/HUP9601566A3/hu unknown
- 1996-06-06 LV LVP-96-176A patent/LV11615B/en unknown
-
1997
- 1997-12-05 FI FI974440A patent/FI974440A/fi not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
CZ289249B6 (cs) | 2001-12-12 |
FI974440A0 (fi) | 1997-12-05 |
IL118484A0 (en) | 1996-09-12 |
NZ286733A (en) | 1998-02-26 |
EP0832069B1 (en) | 2003-03-05 |
LV11615A (lv) | 1996-12-20 |
HRP960270A2 (en) | 1997-12-31 |
IL118484A (en) | 2001-11-25 |
AP9600804A0 (en) | 1997-11-09 |
BR9602628A (pt) | 1998-09-08 |
EP0832069A1 (en) | 1998-04-01 |
SG44952A1 (en) | 1997-12-19 |
CZ164496A3 (en) | 1997-01-15 |
WO1996040640A1 (en) | 1996-12-19 |
LV11615B (en) | 1997-04-20 |
HUP9601566A2 (en) | 1997-09-29 |
HUP9601566A3 (en) | 1998-01-28 |
FI974440A (fi) | 1998-01-27 |
PL314636A1 (en) | 1996-12-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
SI9600183A (en) | Therapeutic amides | |
US5919795A (en) | Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (Apo B) secretion | |
JP2000505810A (ja) | アポb−分泌/mtp阻害性アミド | |
TW200526635A (en) | Hydroxypyrimidinone derivative having HIV integrase inhibitory activity | |
JP2006508033A (ja) | テトラヒドロイソキノリン誘導体 | |
SK13292000A3 (sk) | Antagonisty vitronektínového receptora, spôsob ich výroby, farmaceutický prostriedok s ich obsahom, ich použitie a medziprodukty | |
JP2004537504A (ja) | コリン作用アップレギュレーション及び炎症ダウンレギュレーションを共誘導する化合物、並びにその使用 | |
MX2012005189A (es) | Inhibidores de ire-1-alfa. | |
EP2760839B1 (en) | Pyridinedione carboxamide inhibitors of endothelial lipase | |
JP5149794B2 (ja) | 飽和リンカー基を含有するヘテロアリール置換アミドおよび医薬としてのその使用 | |
KR20000065152A (ko) | 4'-트리플루오로메틸비페닐-2-카복실산2-(2에이치-[1,2,4]트리아졸-3-일메틸)-1,2,3,4-테트라히드로-이소퀴놀린-6-일-아미드를제조하기위한방법및이의중간체 | |
EP1181954A2 (en) | Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (ApoB) secretion | |
JP4685307B2 (ja) | ビトロネクチン受容体アンタゴニスト | |
KR101132599B1 (ko) | 아폽토시스 유도 효과를 갖는 인돌 유도체 | |
ES2257168A1 (es) | Ligandos del receptor 5-ht7. | |
CA2223574C (en) | Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein b (apo b) secretion | |
SK283408B6 (sk) | Amidy a farmaceutické prostriedky na ich báze | |
JP2002522360A (ja) | ビトロネクチン受容体アンタゴニスト | |
AP760A (en) | Biphenyl-2-carboxylic acid-tetrahydro-isoquiolin-6-yl amide derivatives. | |
JPH11514964A (ja) | ビフェニル−2−カルボン酸−テトラヒドロ−イソキノリン−6−イルアミド誘導体の製造と、ミクロソームのトリ剤グリセリド転移タンパク質および(または)アポリポ蛋白質b(アポb)分泌の阻害としての該誘導体の使用 | |
AU1639101A (en) | Therapeutic amides and compositions containing the same | |
AU3585399A (en) | Intermediates for the preparation of therapeutic amides | |
MXPA00008847A (en) | Vitronectin receptor antagonists | |
JPS58942A (ja) | シクロオクチルラニチジン誘導体、その製法及びそれを含む医薬組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
IF | Valid on the event date | ||
KO00 | Lapse of patent |
Effective date: 20060414 |