OA10363A - Therapeutic amides - Google Patents

Therapeutic amides Download PDF

Info

Publication number: OA10363A
Authority: OA; OAPI
Prior art keywords: biphenyl; amide; carboxylic acid; trifluoromethyl; tetrahydroisoquinolin
Prior art date: 1995-06-07

Application number

OA60837A

Other languages

English (en)

Inventor

George Chang

Peter H Dorff

George J Quallich

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-06-07

Filing date

1996-06-07

Publication date

2001-11-15

1995-06-07 Priority claimed from PCT/IB1995/000448 external-priority patent/WO1996040640A1/en

1996-06-07 Application filed by Pfizer filed Critical Pfizer

2001-11-15 Publication of OA10363A publication Critical patent/OA10363A/en

Links

150000001408 amides Chemical class 0.000 title claims description 14
230000001225 therapeutic effect Effects 0.000 title description 2
-1 (C6-C10)aryltio Chemical group 0.000 claims abstract description 107
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 32
125000003118 aryl group Chemical group 0.000 claims abstract description 21
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 17
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
150000003839 salts Chemical class 0.000 claims abstract description 17
125000004423 acyloxy group Chemical group 0.000 claims abstract description 13
125000000041 C6-C10 aryl group Chemical group 0.000 claims abstract description 12
229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 10
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
125000002252 acyl group Chemical group 0.000 claims abstract description 9
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
125000001424 substituent group Chemical group 0.000 claims abstract description 9
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims abstract description 8
125000005842 heteroatom Chemical group 0.000 claims abstract description 8
125000004414 alkyl thio group 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
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 6
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 6
125000004104 aryloxy group Chemical group 0.000 claims abstract description 6
125000006554 (C4-C8) cycloalkenyl group Chemical group 0.000 claims abstract description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
239000001301 oxygen Substances 0.000 claims abstract description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 5
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
125000006413 ring segment Chemical group 0.000 claims abstract description 4
229920001774 Perfluoroether Polymers 0.000 claims abstract description 3
125000004465 cycloalkenyloxy group Chemical group 0.000 claims abstract description 3
125000005592 polycycloalkyl group Polymers 0.000 claims abstract description 3
229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims abstract 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract 2
239000011593 sulfur Substances 0.000 claims abstract 2
150000001875 compounds Chemical class 0.000 claims description 127
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 87
239000002253 acid Substances 0.000 claims description 44
229910052799 carbon Inorganic materials 0.000 claims description 43
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 23
150000003254 radicals Chemical class 0.000 claims description 23
125000003545 alkoxy group Chemical group 0.000 claims description 13
125000005647 linker group Chemical group 0.000 claims description 11
239000000203 mixture Substances 0.000 claims description 10
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
229920006395 saturated elastomer Polymers 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 6
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 6
229940124530 sulfonamide Drugs 0.000 claims description 6
150000003456 sulfonamides Chemical group 0.000 claims description 6
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 6
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical group C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
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 5
125000001544 thienyl group Chemical group 0.000 claims description 5
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 4
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 4
125000004450 alkenylene group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
125000000335 thiazolyl group Chemical group 0.000 claims description 4
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 claims description 3
125000005110 aryl thio group Chemical group 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 claims description 3
125000000842 isoxazolyl group Chemical group 0.000 claims description 3
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 description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000000168 pyrrolyl group Chemical group 0.000 claims description 3
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 claims description 2
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 description 2
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 2
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
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 claims description 2
JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 claims description 2
125000002619 bicyclic group Chemical group 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000002950 monocyclic group Chemical group 0.000 claims description 2
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 claims description 2
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 2
WNDIAFXQKOHFLV-UHFFFAOYSA-N n-[2-(1h-1,2,4-triazol-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(CC2=NNC=N2)CC2)C2=C1 WNDIAFXQKOHFLV-UHFFFAOYSA-N 0.000 claims description 2
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 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 3
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 3
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea group Chemical group NC(=S)N UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims 2
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
AEFLZMREMMKHDV-UHFFFAOYSA-N 1-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)-2-thiophen-2-ylethanone Chemical compound C1CC2=CC(N)=CC=C2CN1C(=O)CC1=CC=CS1 AEFLZMREMMKHDV-UHFFFAOYSA-N 0.000 claims 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 claims 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 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
DWBTXRYWBQNLCR-UHFFFAOYSA-N 2-[(3-nitrophenyl)methyl]-3,4-dihydro-1H-isoquinolin-6-amine Chemical compound C1CC2=CC(N)=CC=C2CN1CC1=CC=CC([N+]([O-])=O)=C1 DWBTXRYWBQNLCR-UHFFFAOYSA-N 0.000 claims 1
ZBEGCYXAHKXKHA-UHFFFAOYSA-N 6-amino-N,N-dimethyl-3,4-dihydro-1H-isoquinoline-2-sulfonamide Chemical compound NC1=CC=C2CN(S(=O)(=O)N(C)C)CCC2=C1 ZBEGCYXAHKXKHA-UHFFFAOYSA-N 0.000 claims 1
HMVQKDXKSNGJMV-UHFFFAOYSA-N N-[2-[(3-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=C(Cl)C=CC=2)CC2)C2=C1 HMVQKDXKSNGJMV-UHFFFAOYSA-N 0.000 claims 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 claims 1
239000004202 carbamide Substances 0.000 claims 1
GHVZCYSYXCFJMA-UHFFFAOYSA-N n-(1-phenylethyl)-6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxamide Chemical compound C=1C=CC=CC=1C(C)NC(=O)N(CC1=CC=2)CCC1=CC=2NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 GHVZCYSYXCFJMA-UHFFFAOYSA-N 0.000 claims 1
JHWRGYDZUYBPRO-UHFFFAOYSA-N n-(2-pentanoyl-3,4-dihydro-1h-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(C(=O)CCCC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 JHWRGYDZUYBPRO-UHFFFAOYSA-N 0.000 claims 1
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 claims 1
XGJYPBLLKVZMKG-UHFFFAOYSA-N n-[2-(1h-imidazol-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=CN=2)CC2)C2=C1 XGJYPBLLKVZMKG-UHFFFAOYSA-N 0.000 claims 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 claims 1
CVHJDCYMGDFQSA-UHFFFAOYSA-N n-[2-(4,5a,6,9,9a,9b-hexahydro-1h-dibenzofuran-4a-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(CC23C(CC=CC2)C2C(CC=CC2)O3)CC2)C2=C1 CVHJDCYMGDFQSA-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
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 claims 1
125000005010 perfluoroalkyl group Chemical group 0.000 claims 1
KTKJCGKOCTXFRX-UHFFFAOYSA-N tert-butyl 6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound 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 1
125000001391 thioamide group Chemical group 0.000 claims 1
125000005843 halogen group Chemical group 0.000 abstract description 6
125000006664 (C1-C3) perfluoroalkyl group Chemical group 0.000 abstract description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 3
125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 43
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
239000000243 solution Substances 0.000 description 41
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 38
238000000034 method Methods 0.000 description 38
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
238000005481 NMR spectroscopy Methods 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 29
239000002904 solvent Substances 0.000 description 28
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 26
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
239000007787 solid Substances 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
229940073584 methylene chloride Drugs 0.000 description 20
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000000047 product Substances 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
239000012044 organic layer Substances 0.000 description 13
238000005160 1H NMR spectroscopy Methods 0.000 description 12
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 12
229920000642 polymer Polymers 0.000 description 12
150000001721 carbon Chemical group 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
239000003921 oil Substances 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
125000004122 cyclic group Chemical group 0.000 description 9
235000019439 ethyl acetate Nutrition 0.000 description 9
239000002502 liposome Substances 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
101150102415 Apob gene Proteins 0.000 description 8
150000002009 diols Chemical class 0.000 description 8
230000000694 effects Effects 0.000 description 8
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
201000001320 Atherosclerosis Diseases 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
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BADIKWAGMZXDJE-UHFFFAOYSA-N n-[1-[2-(2-methylphenyl)acetyl]-1,2,3,4-tetrahydroisoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CC1=CC=CC=C1CC(=O)C1C2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CCN1 BADIKWAGMZXDJE-UHFFFAOYSA-N 0.000 description 1
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 1
UEZDQGILGUGPBI-UHFFFAOYSA-N n-[2-(2-thiophen-3-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)CC3=CSC=C3)C2=C1 UEZDQGILGUGPBI-UHFFFAOYSA-N 0.000 description 1
NCWVXMIZHRWLLQ-UHFFFAOYSA-N n-[2-(3-cyclopentylpropanoyl)-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)CCC3CCCC3)C2=C1 NCWVXMIZHRWLLQ-UHFFFAOYSA-N 0.000 description 1
YSUQGHLKNKSWBD-UHFFFAOYSA-N n-[2-(dimethylsulfamoyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(S(=O)(=O)N(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 YSUQGHLKNKSWBD-UHFFFAOYSA-N 0.000 description 1
DDIQYNDUIFCEAY-UHFFFAOYSA-N n-[2-(furan-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=2OC=CC=2)CC2)C2=C1 DDIQYNDUIFCEAY-UHFFFAOYSA-N 0.000 description 1
ATYGMQZDELKKFL-UHFFFAOYSA-N n-[2-[(2-fluorophenyl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound FC1=CC=CC=C1CN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 ATYGMQZDELKKFL-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
RIOGTIQYMCSVQE-UHFFFAOYSA-N n-[2-[(2-methyl-1h-indol-3-yl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CC=1NC2=CC=CC=C2C=1CN(CC1=CC=2)CCC1=CC=2NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 RIOGTIQYMCSVQE-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
BQBWUBKROPEBDY-UHFFFAOYSA-N n-benzyl-6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)NCC=3C=CC=CC=3)C2=C1 BQBWUBKROPEBDY-UHFFFAOYSA-N 0.000 description 1
SKSUWQXFVLLGSL-UHFFFAOYSA-N n-pyridin-2-yl-6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2)C(=O)NC=3N=CC=CC=3)C2=C1 SKSUWQXFVLLGSL-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
239000006186 oral dosage form Substances 0.000 description 1
238000003305 oral gavage Methods 0.000 description 1
239000007968 orange flavor Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000002971 oxazolyl group Chemical group 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
230000036961 partial effect Effects 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
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
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150000003904 phospholipids Chemical class 0.000 description 1
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 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
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
229920001223 polyethylene glycol Polymers 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
239000004323 potassium nitrate Substances 0.000 description 1
235000010333 potassium nitrate Nutrition 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 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
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
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001953 recrystallisation 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
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
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
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
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
125000000464 thioxo group Chemical group S=* 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- 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
- A61P3/06—Antihyperlipidemics
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- 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
- 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

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Diabetes (AREA)
Obesity (AREA)
Hematology (AREA)
Endocrinology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Emergency Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

OA60837A 1995-06-07 1996-06-07 Therapeutic amides OA10363A (en)

Applications Claiming Priority (1)

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

Publications (1)

Publication Number	Publication Date
OA10363A true OA10363A (en)	2001-11-15

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ID=11004342

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA60837A OA10363A (en)	1995-06-07	1996-06-07	Therapeutic amides

Country Status (20)

Country	Link
US (1)	US5919795A (ro)
KR (1)	KR100225713B1 (ro)
AR (1)	AR003424A1 (ro)
AT (1)	ATE233734T1 (ro)
AU (1)	AU703493B2 (ro)
BG (1)	BG62442B1 (ro)
CO (1)	CO4440626A1 (ro)
DE (1)	DE69529849T2 (ro)
DK (1)	DK0832069T3 (ro)
DZ (1)	DZ2045A1 (ro)
IL (3)	IL135376A0 (ro)
MA (1)	MA23895A1 (ro)
MX (1)	MX9709914A (ro)
OA (1)	OA10363A (ro)
RO (1)	RO116897B1 (ro)
RU (1)	RU2141478C1 (ro)
TN (1)	TNSN96085A1 (ro)
TR (1)	TR199600481A2 (ro)
TW (1)	TW476756B (ro)
YU (1)	YU35296A (ro)

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Publication number	Priority date	Publication date	Assignee	Title
TR199802163T2 (xx) *	1996-04-30	1999-02-22	Pfizer Inc.	4'-Triflorometilbifenil-2-karboksilik asit
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1995
- 1995-06-07 DK DK95918722T patent/DK0832069T3/da active
- 1995-06-07 DE DE69529849T patent/DE69529849T2/de not_active Expired - Fee Related
- 1995-06-07 AT AT95918722T patent/ATE233734T1/de not_active IP Right Cessation
- 1995-06-07 MX MX9709914A patent/MX9709914A/es not_active IP Right Cessation
- 1995-06-07 US US08/952,507 patent/US5919795A/en not_active Expired - Fee Related
1996
- 1996-04-19 TW TW085104696A patent/TW476756B/zh not_active IP Right Cessation
- 1996-05-30 IL IL13537696A patent/IL135376A0/xx not_active IP Right Cessation
- 1996-05-30 IL IL13537596A patent/IL135375A/en not_active IP Right Cessation
- 1996-05-30 IL IL13537796A patent/IL135377A0/xx not_active IP Right Cessation
- 1996-06-03 AR ARP960102871A patent/AR003424A1/es unknown
- 1996-06-05 DZ DZ960089A patent/DZ2045A1/fr active
- 1996-06-05 BG BG100637A patent/BG62442B1/bg unknown
- 1996-06-05 KR KR1019960020168A patent/KR100225713B1/ko not_active Expired - Fee Related
- 1996-06-06 YU YU35296A patent/YU35296A/sh unknown
- 1996-06-06 MA MA24265A patent/MA23895A1/fr unknown
- 1996-06-06 TR TR96/00481A patent/TR199600481A2/xx unknown
- 1996-06-06 TN TNTNSN96085A patent/TNSN96085A1/fr unknown
- 1996-06-06 AU AU54784/96A patent/AU703493B2/en not_active Ceased
- 1996-06-06 RU RU96111018A patent/RU2141478C1/ru not_active IP Right Cessation
- 1996-06-07 RO RO96-01181A patent/RO116897B1/ro unknown
- 1996-06-07 CO CO96029732A patent/CO4440626A1/es unknown
- 1996-06-07 OA OA60837A patent/OA10363A/en unknown

Also Published As

Publication number	Publication date
IL135377A (en)	2001-05-20
KR970003589A (ko)	1997-01-28
TR199600481A2 (tr)	1996-12-21
US5919795A (en)	1999-07-06
IL135375A (en)	2001-07-24
DZ2045A1 (fr)	2002-07-21
IL135377A0 (en)	2001-05-20
YU35296A (sh)	1999-06-15
MX9709914A (es)	1998-03-31
IL135376A (en)	2001-05-20
TNSN96085A1 (fr)	2005-03-15
TW476756B (en)	2002-02-21
IL135376A0 (en)	2001-05-20
AU703493B2 (en)	1999-03-25
MA23895A1 (fr)	1996-12-31
IL135375A0 (en)	2001-05-20
KR100225713B1 (ko)	1999-10-15
ATE233734T1 (de)	2003-03-15
DK0832069T3 (da)	2003-04-22
DE69529849D1 (de)	2003-04-10
DE69529849T2 (de)	2003-09-04
BG100637A (bg)	1997-03-31
AR003424A1 (es)	1998-08-05
BG62442B1 (bg)	1999-11-30
RU2141478C1 (ru)	1999-11-20
AU5478496A (en)	1996-12-19
CO4440626A1 (es)	1997-05-07
RO116897B1 (ro)	2001-07-30

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OA10363A (en)	2001-11-15	Therapeutic amides
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EP1778642A1 (en)	2007-05-02	5-ht7 receptor antagonosts
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SK72696A3 (en)	1997-11-05	Amides and pharmauceutical compositions on their base
JPH11514964A (ja)	1999-12-21	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)	2001-04-26	Therapeutic amides and compositions containing the same
AU3585399A (en)	1999-09-16	Intermediates for the preparation of therapeutic amides
EP1102587A2 (en)	2001-05-30	Vitronectin receptor antagonists
ES2257167B1 (es)	2007-06-01	Inhibidores del receptor 5-ht7.
CN103387567B (zh)	2015-03-11	一种nept类化合物及其制备方法与应用
SK166199A3 (en)	2000-06-12	5-naphthalen-1-yl-1,3-dioxane derivatives, preparation and therapeutic application