HRP970642A2 - Apo b-secretion/mtp inhibitory amides - Google Patents

Info

Publication number

HRP970642A2

HRP970642A2 HR60/032,307A HRP970642A HRP970642A2 HR P970642 A2 HRP970642 A2 HR P970642A2 HR P970642 A HRP970642 A HR P970642A HR P970642 A2 HRP970642 A2 HR P970642A2

Authority

HR

Croatia

Prior art keywords

compound

trifluoromethylbiphenyl

amide

carboxylic acid

tetrahydroisoquinolin

Prior art date

1996-11-27

Links

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• 150000001408 amides Chemical class 0.000 title claims description 10
• 230000002401 inhibitory effect Effects 0.000 title claims description 8
• 150000001875 compounds Chemical class 0.000 claims description 301
• 238000000034 method Methods 0.000 claims description 187
• -1 cyano, nitro, oxo, thioxo, aminosulfonyl Chemical group 0.000 claims description 69
• 125000000623 heterocyclic group Chemical group 0.000 claims description 40
• 150000003839 salts Chemical class 0.000 claims description 37
• 239000003112 inhibitor Substances 0.000 claims description 33
• 239000002253 acid Substances 0.000 claims description 32
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 32
• 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 31
• 125000003282 alkyl amino group Chemical group 0.000 claims description 31
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
• 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 229920006395 saturated elastomer Polymers 0.000 claims description 27
• 125000001424 substituent group Chemical group 0.000 claims description 27
• 238000011282 treatment Methods 0.000 claims description 27
• 239000000203 mixture Substances 0.000 claims description 23
• 229910052757 nitrogen Inorganic materials 0.000 claims description 23
• 229910052736 halogen Inorganic materials 0.000 claims description 22
• 125000002252 acyl group Chemical group 0.000 claims description 21
• 150000001412 amines Chemical class 0.000 claims description 21
• 125000000217 alkyl group Chemical group 0.000 claims description 20
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 19
• 229920001774 Perfluoroether Polymers 0.000 claims description 19
• 125000004423 acyloxy group Chemical group 0.000 claims description 17
• 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 16
• 125000004442 acylamino group Chemical group 0.000 claims description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
• 150000002367 halogens Chemical group 0.000 claims description 15
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 14
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 14
• 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims description 13
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 13
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 13
• 125000004414 alkyl thio group Chemical group 0.000 claims description 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 12
• 201000001320 Atherosclerosis Diseases 0.000 claims description 11
• 208000008589 Obesity Diseases 0.000 claims description 11
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
• 235000020824 obesity Nutrition 0.000 claims description 11
• 125000006413 ring segment Chemical group 0.000 claims description 11
• 230000028327 secretion Effects 0.000 claims description 11
• 229910052717 sulfur Chemical group 0.000 claims description 11
• 239000011593 sulfur Chemical group 0.000 claims description 11
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [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
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 150000004677 hydrates Chemical class 0.000 claims description 10
• 208000006575 hypertriglyceridemia Diseases 0.000 claims description 10
• 229910052760 oxygen Inorganic materials 0.000 claims description 10
• 239000001301 oxygen Substances 0.000 claims description 10
• 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims description 9
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 9
• 206010012601 diabetes mellitus Diseases 0.000 claims description 9
• 239000003085 diluting agent Substances 0.000 claims description 9
• 239000004059 squalene synthase inhibitor Substances 0.000 claims description 9
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 230000009467 reduction Effects 0.000 claims description 8
• 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 claims description 7
• 241000124008 Mammalia Species 0.000 claims description 7
• 206010033645 Pancreatitis Diseases 0.000 claims description 7
• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 7
• 238000005859 coupling reaction Methods 0.000 claims description 7
• 230000008569 process Effects 0.000 claims description 7
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 6
• 239000012458 free base Substances 0.000 claims description 6
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 238000007363 ring formation reaction Methods 0.000 claims description 6
• 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
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 5
• 125000003118 aryl group Chemical group 0.000 claims description 5
• 229960005370 atorvastatin Drugs 0.000 claims description 5
• 238000010511 deprotection reaction Methods 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 239000001257 hydrogen Substances 0.000 claims description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 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
• 230000008878 coupling Effects 0.000 claims description 4
• 238000010168 coupling process Methods 0.000 claims description 4
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 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
• JQSPGHFDUJJOHI-UHFFFAOYSA-N 2-[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinolin-2-yl]acetic acid Chemical compound C=1C=C2CN(CC(=O)O)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 JQSPGHFDUJJOHI-UHFFFAOYSA-N 0.000 claims description 3
• SLLQIJSARNKDJN-UHFFFAOYSA-N 2-[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinolin-2-yl]ethyl acetate Chemical compound C=1C=C2CN(CCOC(=O)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 SLLQIJSARNKDJN-UHFFFAOYSA-N 0.000 claims description 3
• GXWSFKGVGIZZET-UHFFFAOYSA-N 2-[6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinolin-2-yl]ethyl n,n-dimethylcarbamate Chemical compound C=1C=C2CN(CCOC(=O)N(C)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 GXWSFKGVGIZZET-UHFFFAOYSA-N 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
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-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
• 239000003963 antioxidant agent Substances 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
• 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
• 125000000842 isoxazolyl 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
• ONIOEZPCTYPMKO-UHFFFAOYSA-N n-(2-piperidin-4-yl-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)C3CCNCC3)C2=C1 ONIOEZPCTYPMKO-UHFFFAOYSA-N 0.000 claims description 3
• IPIRHKWGJUGBFP-UHFFFAOYSA-N n-[1-(2-phenylethyl)-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(CCC=2C=CC=CC=2)NCC2)C2=C1 IPIRHKWGJUGBFP-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• DJLMIXIBPMWLNC-UHFFFAOYSA-N n-[2-(2-acetamidoethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCNC(=O)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 DJLMIXIBPMWLNC-UHFFFAOYSA-N 0.000 claims description 3
• TXGWZSKPSWADFW-UHFFFAOYSA-N n-[2-(2-aminoethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCN)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 TXGWZSKPSWADFW-UHFFFAOYSA-N 0.000 claims description 3
• RTBXDSJYPXWTRB-UHFFFAOYSA-N n-[2-(2-cyanoethyl)-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#N)CC2)C2=C1 RTBXDSJYPXWTRB-UHFFFAOYSA-N 0.000 claims description 3
• FMVTZLHEMMBKOR-UHFFFAOYSA-N n-[2-(2-ethoxyethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCOCC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 FMVTZLHEMMBKOR-UHFFFAOYSA-N 0.000 claims description 3
• BKZORRRJLOXWTI-UHFFFAOYSA-N n-[2-(2-formamidoethyl)-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(CCNC=O)CC2)C2=C1 BKZORRRJLOXWTI-UHFFFAOYSA-N 0.000 claims description 3
• RQBZZHGIDBMSQC-UHFFFAOYSA-N n-[2-(2-methoxyethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCOC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 RQBZZHGIDBMSQC-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
• IROVRPWUEUAUCC-UHFFFAOYSA-N n-[2-(3-methoxypropyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCCOC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IROVRPWUEUAUCC-UHFFFAOYSA-N 0.000 claims description 3
• DBBZPSPJXFAVFC-UHFFFAOYSA-N n-[2-[2-(1-methylpyrrol-2-yl)ethyl]-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CN1C=CC=C1CCN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 DBBZPSPJXFAVFC-UHFFFAOYSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 239000011664 nicotinic acid Substances 0.000 claims description 3
• 229960003512 nicotinic acid Drugs 0.000 claims description 3
• 235000001968 nicotinic acid Nutrition 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 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
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 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
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
• 150000002537 isoquinolines Chemical class 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
• 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 description 2
• 125000005309 thioalkoxy group Chemical group 0.000 claims description 2
• 125000005490 tosylate group Chemical group 0.000 claims description 2
• 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims 2
• 102100028888 Hydroxymethylglutaryl-CoA synthase, cytoplasmic Human genes 0.000 claims 2
• 230000003078 antioxidant effect Effects 0.000 claims 2
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
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• 239000000460 chlorine Substances 0.000 description 97
• 238000005160 1H NMR spectroscopy Methods 0.000 description 86
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
• 239000000243 solution Substances 0.000 description 64
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• 238000006243 chemical reaction Methods 0.000 description 41
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• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 34
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
• 239000007787 solid Substances 0.000 description 28
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
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• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
• 239000002904 solvent Substances 0.000 description 26
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
• 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 23
• 108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 23
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
• 230000015572 biosynthetic process Effects 0.000 description 20
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