SK65499A3 - Apo b-secretion/mtp inhibitory amides - Google Patents
Apo b-secretion/mtp inhibitory amides Download PDFInfo
- Publication number
- SK65499A3 SK65499A3 SK654-99A SK65499A SK65499A3 SK 65499 A3 SK65499 A3 SK 65499A3 SK 65499 A SK65499 A SK 65499A SK 65499 A3 SK65499 A3 SK 65499A3
- Authority
- SK
- Slovakia
- Prior art keywords
- amide
- carbon atoms
- formula
- group
- compound
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- 150000001408 amides Chemical class 0.000 title claims description 54
- 230000002401 inhibitory effect Effects 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 242
- 238000000034 method Methods 0.000 claims abstract description 149
- 239000003112 inhibitor Substances 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 230000008569 process Effects 0.000 claims abstract description 31
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 12
- 208000008589 Obesity Diseases 0.000 claims abstract description 12
- 235000020824 obesity Nutrition 0.000 claims abstract description 12
- 208000006575 hypertriglyceridemia Diseases 0.000 claims abstract description 11
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims abstract description 10
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims abstract description 10
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 10
- 150000004677 hydrates Chemical class 0.000 claims abstract description 10
- 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 claims abstract description 8
- 206010033645 Pancreatitis Diseases 0.000 claims abstract description 8
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims abstract description 7
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims abstract description 7
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims abstract description 7
- 239000004059 squalene synthase inhibitor Substances 0.000 claims abstract description 7
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 4
- 239000011664 nicotinic acid Substances 0.000 claims abstract description 4
- 229960003512 nicotinic acid Drugs 0.000 claims abstract description 4
- 235000001968 nicotinic acid Nutrition 0.000 claims abstract description 4
- 102100028888 Hydroxymethylglutaryl-CoA synthase, cytoplasmic Human genes 0.000 claims abstract 3
- -1 cyano, nitro, oxo, thioxo, aminosulfonyl Chemical group 0.000 claims description 119
- 125000004432 carbon atom Chemical group C* 0.000 claims description 69
- 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 61
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 44
- 239000002253 acid Substances 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 229920006395 saturated elastomer Polymers 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 229920001774 Perfluoroether Polymers 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical group 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000002252 acyl group Chemical group 0.000 claims description 19
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 18
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 125000004414 alkyl thio group Chemical group 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000004423 acyloxy group Chemical group 0.000 claims description 15
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 15
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 13
- 125000004442 acylamino group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 12
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 11
- 125000006413 ring segment Chemical group 0.000 claims description 11
- 230000028327 secretion Effects 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 239000011593 sulfur Substances 0.000 claims description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 10
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 5
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 229960005370 atorvastatin Drugs 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 5
- 229940123495 Squalene synthetase inhibitor Drugs 0.000 claims description 4
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 229940122498 Gene expression inhibitor Drugs 0.000 claims description 3
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 3
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- DWLVWMUCHSLGSU-UHFFFAOYSA-N dimethylcarbamic acid Chemical compound CN(C)C(O)=O DWLVWMUCHSLGSU-UHFFFAOYSA-N 0.000 claims description 3
- 229960003765 fluvastatin Drugs 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 229960004844 lovastatin Drugs 0.000 claims description 3
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 3
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 3
- FJULIZHZIHXKSK-UHFFFAOYSA-N methyl n-[2-[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinolin-2-yl]ethyl]carbamate Chemical compound C=1C=C2CN(CCNC(=O)OC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 FJULIZHZIHXKSK-UHFFFAOYSA-N 0.000 claims description 3
- XMVILEXDBBLNDS-UHFFFAOYSA-N n-[2-(2-pyridin-2-ylethyl)-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(CCC=2N=CC=CC=2)CC2)C2=C1 XMVILEXDBBLNDS-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229960002965 pravastatin Drugs 0.000 claims description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 3
- 229960002855 simvastatin Drugs 0.000 claims description 3
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- MRLSUJLQPMFALJ-UHFFFAOYSA-N n-(1-pentyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2C(CCCCC)NCCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 MRLSUJLQPMFALJ-UHFFFAOYSA-N 0.000 claims description 2
- GZBTYVSXAPULFM-UHFFFAOYSA-N n-[2-(2,2-diphenylethyl)-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(C=2C=CC=CC=2)C=2C=CC=CC=2)CC2)C2=C1 GZBTYVSXAPULFM-UHFFFAOYSA-N 0.000 claims description 2
- QPGMSBVQWMQDSX-UHFFFAOYSA-N n-[2-(6-amino-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]acetamide Chemical compound NC1=CC=C2CN(CCNC(=O)C)CCC2=C1 QPGMSBVQWMQDSX-UHFFFAOYSA-N 0.000 claims description 2
- NHRFLOWUMZHRBN-UHFFFAOYSA-N n-[2-[2-(diethylamino)-2-oxoethyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CC(=O)N(CC)CC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 NHRFLOWUMZHRBN-UHFFFAOYSA-N 0.000 claims description 2
- NTTVZTQFRYTVHG-UHFFFAOYSA-N n-[2-[2-(dimethylamino)-2-oxoethyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CC(=O)N(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 NTTVZTQFRYTVHG-UHFFFAOYSA-N 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims 2
- 230000003078 antioxidant effect Effects 0.000 claims 2
- 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 1
- LBKMGNSFTXJPCL-UHFFFAOYSA-N N-[2-(2-amino-3-oxopropyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C(=O)C(CN1CC2=CC=C(C=C2CC1)NC(=O)C=1C(=CC=CC1)C1=CC=C(C=C1)C(F)(F)F)N LBKMGNSFTXJPCL-UHFFFAOYSA-N 0.000 claims 1
- QKBCZAAUPIZRQQ-UHFFFAOYSA-N N-[2-(6-amino-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]propanamide Chemical compound CCC(=O)NCCN1CCC2=C(C1)C=CC(=C2)N QKBCZAAUPIZRQQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims 1
- 150000002537 isoquinolines Chemical class 0.000 claims 1
- QYKMYZGCUWNESH-UHFFFAOYSA-N n-[2-[2-(methanesulfonamido)ethyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCNS(=O)(=O)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 QYKMYZGCUWNESH-UHFFFAOYSA-N 0.000 claims 1
- TXYOBYQOKHTGHM-UHFFFAOYSA-N n-[2-[2-(methylcarbamoylamino)ethyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCNC(=O)NC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 TXYOBYQOKHTGHM-UHFFFAOYSA-N 0.000 claims 1
- OWGMVMTWHXUUEQ-UHFFFAOYSA-N n-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCNC(=O)C(F)(F)F)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 OWGMVMTWHXUUEQ-UHFFFAOYSA-N 0.000 claims 1
- NPDUIZBPQWFWSX-UHFFFAOYSA-N n-[2-[3-(dimethylamino)-3-oxopropyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCC(=O)N(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 NPDUIZBPQWFWSX-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 33
- 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 abstract description 17
- 230000001906 cholesterol absorption Effects 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 239000000543 intermediate Substances 0.000 abstract description 7
- 235000012000 cholesterol Nutrition 0.000 abstract description 6
- 230000014509 gene expression Effects 0.000 abstract description 3
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 abstract description 3
- 229920000080 bile acid sequestrant Polymers 0.000 abstract description 2
- 229940096699 bile acid sequestrants Drugs 0.000 abstract description 2
- 229940125753 fibrate Drugs 0.000 abstract description 2
- 239000003456 ion exchange resin Substances 0.000 abstract description 2
- 229920003303 ion-exchange polymer Polymers 0.000 abstract description 2
- 239000008177 pharmaceutical agent Substances 0.000 abstract description 2
- 235000006708 antioxidants Nutrition 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 139
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 129
- 238000005481 NMR spectroscopy Methods 0.000 description 89
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 239000000203 mixture Substances 0.000 description 61
- 239000000243 solution Substances 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 230000002829 reductive effect Effects 0.000 description 37
- 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 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- 238000003786 synthesis reaction Methods 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 26
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 25
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
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- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
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- 238000007911 parenteral administration Methods 0.000 description 1
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- 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
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
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- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001184 polypeptide 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
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000069 prophylactic 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
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
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- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
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- HWECMADGHQKSLK-OLTWBHDESA-N rosenonolactone Chemical class C([C@H]1C(=O)C[C@@H]23)[C@@](C)(C=C)CC[C@@]1(C)[C@@]31CCC[C@]2(C)C(=O)O1 HWECMADGHQKSLK-OLTWBHDESA-N 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
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- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000005201 scrubbing Methods 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
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical class C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- DIORMHZUUKOISG-UHFFFAOYSA-N sulfoformic acid Chemical class OC(=O)S(O)(=O)=O DIORMHZUUKOISG-UHFFFAOYSA-N 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 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 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
- 210000001519 tissue Anatomy 0.000 description 1
- 239000006208 topical dosage form Substances 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 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
- 150000003672 ureas Chemical class 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 150000003952 β-lactams Chemical class 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- 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
- 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
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- 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)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (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)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
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US3230796P | 1996-11-27 | 1996-11-27 | |
PCT/IB1997/001368 WO1998023593A1 (en) | 1996-11-27 | 1997-11-03 | Apo b-secretion/mtp inhibitory amides |
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SK65499A3 true SK65499A3 (en) | 2001-05-10 |
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SK654-99A SK65499A3 (en) | 1996-11-27 | 1997-11-03 | Apo b-secretion/mtp inhibitory amides |
Country Status (34)
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US (1) | US6121283A (zh) |
EP (1) | EP0944602A1 (zh) |
JP (1) | JP3270764B2 (zh) |
KR (1) | KR100334567B1 (zh) |
CN (2) | CN1238764A (zh) |
AP (1) | AP804A (zh) |
AR (1) | AR010309A1 (zh) |
AU (1) | AU716151B2 (zh) |
BG (2) | BG103434A (zh) |
BR (1) | BR9714364A (zh) |
CA (1) | CA2272719C (zh) |
CZ (1) | CZ292160B6 (zh) |
DZ (1) | DZ2358A1 (zh) |
EA (1) | EA001539B1 (zh) |
GT (1) | GT199700122A (zh) |
HN (1) | HN1997000144A (zh) |
HR (1) | HRP970642A2 (zh) |
ID (1) | ID18995A (zh) |
IL (1) | IL129744A0 (zh) |
IS (1) | IS5040A (zh) |
MA (1) | MA26451A1 (zh) |
NO (1) | NO312760B1 (zh) |
NZ (1) | NZ335162A (zh) |
OA (1) | OA11050A (zh) |
PA (1) | PA8441601A1 (zh) |
PE (1) | PE17199A1 (zh) |
SK (1) | SK65499A3 (zh) |
TN (1) | TNSN97193A1 (zh) |
TR (1) | TR199901180T2 (zh) |
TW (1) | TW502023B (zh) |
UY (1) | UY24789A1 (zh) |
WO (1) | WO1998023593A1 (zh) |
YU (1) | YU23499A (zh) |
ZA (1) | ZA9710641B (zh) |
Families Citing this family (93)
Publication number | Priority date | Publication date | Assignee | Title |
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US6642268B2 (en) | 1994-09-13 | 2003-11-04 | G.D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors |
US6262277B1 (en) | 1994-09-13 | 2001-07-17 | G.D. Searle And Company | Intermediates and processes for the preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake |
MX9709914A (es) * | 1995-06-07 | 1998-03-31 | Pfizer | Derivados de acido bifenil-2-carboxilico-tetrahidro-isoquinolin-6-ilo, su preparacion y el uso de los mismos. |
GB9708805D0 (en) | 1997-05-01 | 1997-06-25 | Smithkline Beecham Plc | Compounds |
US5968950A (en) * | 1997-06-23 | 1999-10-19 | Pfizer Inc | Apo B-secretion/MTP inhibitor hydrochloride salt |
GB9810876D0 (en) | 1998-05-20 | 1998-07-22 | Smithkline Beecham Plc | Compounds |
AU4543899A (en) | 1998-06-08 | 1999-12-30 | Advanced Medicine, Inc. | Multibinding inhibitors of microsomal triglyceride transferase protein |
CZ20011270A3 (cs) | 1998-10-08 | 2001-09-12 | Smithkline Beecham Plc | Tetrahydrobenzazepinové deriváty vhodné jako modulátory dopaminových receptorů D3 |
GB9826412D0 (en) * | 1998-12-03 | 1999-01-27 | Glaxo Group Ltd | Chemical compounds |
BR9916564A (pt) * | 1998-12-23 | 2002-01-29 | Searle Llc | Combinações para indicações cardiovasculares |
ATE242007T1 (de) | 1998-12-23 | 2003-06-15 | Searle Llc | Kombinationen von cholesteryl ester transfer protein inhibitoren und nicotinsäure derivaten für kardiovaskuläre indikationen |
EA005815B1 (ru) * | 1998-12-23 | 2005-06-30 | Джи.Ди.Сирл Ллс | Комбинация ингибиторов транспорта желчных кислот в подвздошной кишке и ингибиторов белка, переносящего эфиры холестерина, для сердечно-сосудистых показаний |
DE19929065A1 (de) * | 1999-06-25 | 2000-12-28 | Bayer Ag | Kombination von MTP-Inhibitoren und HMG-CoA-Reduktase-Inhibitoren und ihre Verwendung in Arzneimitteln |
DE19929031A1 (de) * | 1999-06-25 | 2000-12-28 | Bayer Ag | Kombination von MTP-Inhibitoren und Lipidsenkern und ihre Verwendung in Arzneimitteln |
DE19929012A1 (de) * | 1999-06-25 | 2000-12-28 | Bayer Ag | Kombination von MTP-Inhibitoren und stoffwechselbeeinflussenden Wirkstoffen und ihre Verwendung in Arzneimitteln |
WO2001005767A1 (en) * | 1999-07-20 | 2001-01-25 | Novartis Ag | Organic compounds |
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 |
CA2324801A1 (en) * | 1999-11-10 | 2001-05-10 | Andrew Gordon Swick | Use of apo b secretion/mtp inhibitors and anti-obesity agents |
CA2324800A1 (en) * | 1999-11-10 | 2001-05-10 | Mary Anne Hickman | Use of apo b secretion/mtp inhibitors |
IL139450A0 (en) * | 1999-11-10 | 2001-11-25 | Pfizer Prod Inc | Methods of administering apo b-secretion/mtp inhibitors |
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