AU8061894A - 4,5-diphenylimidazole derivatives, their preparation and their use as acyl coenzyme A: cholesterol-0-acyl-transferase (ACAT) inhibitor - Google Patents
4,5-diphenylimidazole derivatives, their preparation and their use as acyl coenzyme A: cholesterol-0-acyl-transferase (ACAT) inhibitorInfo
- Publication number
- AU8061894A AU8061894A AU80618/94A AU8061894A AU8061894A AU 8061894 A AU8061894 A AU 8061894A AU 80618/94 A AU80618/94 A AU 80618/94A AU 8061894 A AU8061894 A AU 8061894A AU 8061894 A AU8061894 A AU 8061894A
- Authority
- AU
- Australia
- Prior art keywords
- group
- alkyl
- diphenylimidazole
- compound
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- -1 acyl coenzyme A Chemical compound 0.000 title claims description 41
- 238000002360 preparation method Methods 0.000 title claims description 7
- 239000003112 inhibitor Substances 0.000 title claims description 3
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 title description 5
- 239000005516 coenzyme A Substances 0.000 title description 5
- 229940093530 coenzyme a Drugs 0.000 title description 5
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 title description 5
- CPHGOBGXZQKCKI-UHFFFAOYSA-N 4,5-diphenyl-1h-imidazole Chemical class N1C=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 CPHGOBGXZQKCKI-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 116
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000004104 aryloxy group Chemical group 0.000 claims description 13
- 239000001294 propane Substances 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000029078 coronary artery disease Diseases 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- FBWBTFNVQHJOJQ-UHFFFAOYSA-N 2-[3-(1,3-dioxolan-2-yl)-5-[(4,5-diphenyl-1h-imidazol-2-yl)sulfanyl]pentyl]sulfanyl-4,5-diphenyl-1h-imidazole Chemical compound N=1C(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)NC=1SCCC(C1OCCO1)CCSC(N1)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 FBWBTFNVQHJOJQ-UHFFFAOYSA-N 0.000 claims description 3
- FQEVAKNTZQKYQB-UHFFFAOYSA-N 5-[(4,5-diphenyl-1h-imidazol-2-yl)sulfanyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1SC1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 FQEVAKNTZQKYQB-UHFFFAOYSA-N 0.000 claims description 3
- 230000000879 anti-atherosclerotic effect Effects 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- BSTTXKURPSPUML-UHFFFAOYSA-N 1-(2,4-difluorophenoxy)-3-[(4,5-diphenyl-1h-imidazol-2-yl)sulfanyl]propan-2-ol Chemical compound N=1C(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)NC=1SCC(O)COC1=CC=C(F)C=C1F BSTTXKURPSPUML-UHFFFAOYSA-N 0.000 claims description 2
- PTYQNPOWJOPIBC-UHFFFAOYSA-N 1-[5-[(4,5-diphenyl-1h-imidazol-2-yl)sulfinyl]pentyl]imidazo[1,2-b]pyrazole Chemical compound C1=CN2N=CC=C2N1CCCCCS(=O)C(N1)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 PTYQNPOWJOPIBC-UHFFFAOYSA-N 0.000 claims description 2
- FDXKRXYHIYSKFM-UHFFFAOYSA-N 2-[3-(2,4-difluorophenoxy)propylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound FC1=CC(F)=CC=C1OCCCSC1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 FDXKRXYHIYSKFM-UHFFFAOYSA-N 0.000 claims description 2
- ZEZDVACBQNQOIK-UHFFFAOYSA-N 2-[3-(2,5-dimethylphenoxy)propylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound CC1=CC=C(C)C(OCCCSC=2NC(=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 ZEZDVACBQNQOIK-UHFFFAOYSA-N 0.000 claims description 2
- UNHAHZDJQFVNHN-UHFFFAOYSA-N 2-[3-(4-methylphenoxy)propylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound C1=CC(C)=CC=C1OCCCSC1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 UNHAHZDJQFVNHN-UHFFFAOYSA-N 0.000 claims description 2
- QVAGSPXOMLCLPU-UHFFFAOYSA-N 2-[5-(2,4-difluorophenoxy)pentylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound FC1=CC(F)=CC=C1OCCCCCSC1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 QVAGSPXOMLCLPU-UHFFFAOYSA-N 0.000 claims description 2
- VXSHEDCJJNUKJF-UHFFFAOYSA-N 2-[5-(2,5-dimethylphenoxy)pentylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound CC1=CC=C(C)C(OCCCCCSC=2NC(=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 VXSHEDCJJNUKJF-UHFFFAOYSA-N 0.000 claims description 2
- AVKOGGRBMYCVSB-UHFFFAOYSA-N 2-[5-(3-methoxyphenoxy)pentylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound COC1=CC=CC(OCCCCCSC=2NC(=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 AVKOGGRBMYCVSB-UHFFFAOYSA-N 0.000 claims description 2
- GKEYZYYRGYCGET-UHFFFAOYSA-N 2-[5-(4-chlorophenoxy)pentylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound C1=CC(Cl)=CC=C1OCCCCCSC1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 GKEYZYYRGYCGET-UHFFFAOYSA-N 0.000 claims description 2
- GIZFHMWXPAGCTC-UHFFFAOYSA-N 2-[5-(4-fluorophenoxy)pentylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound C1=CC(F)=CC=C1OCCCCCSC1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 GIZFHMWXPAGCTC-UHFFFAOYSA-N 0.000 claims description 2
- GYTNCNWKDMDEMG-UHFFFAOYSA-N 2-[5-(4-nitrophenoxy)pentylsulfanyl]-4,5-diphenyl-1h-imidazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCCCCSC1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 GYTNCNWKDMDEMG-UHFFFAOYSA-N 0.000 claims description 2
- CATKKEFQYVLVOD-UHFFFAOYSA-N 2-[5-[(4,5-diphenyl-1h-imidazol-2-yl)sulfanyl]pentoxy]pyridine Chemical compound N=1C(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)NC=1SCCCCCOC1=CC=CC=N1 CATKKEFQYVLVOD-UHFFFAOYSA-N 0.000 claims description 2
- OUBFZDMHYDKHLG-UHFFFAOYSA-N 4,5-diphenyl-2-[5-(2,3,5-trimethylphenoxy)pentylsulfanyl]-1h-imidazole Chemical compound CC1=CC(C)=C(C)C(OCCCCCSC=2NC(=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 OUBFZDMHYDKHLG-UHFFFAOYSA-N 0.000 claims description 2
- ZTCKPOGRHMFCHI-UHFFFAOYSA-N 4,5-diphenyl-2-[5-[3-(trifluoromethyl)phenoxy]pentylsulfanyl]-1h-imidazole Chemical compound FC(F)(F)C1=CC=CC(OCCCCCSC=2NC(=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 ZTCKPOGRHMFCHI-UHFFFAOYSA-N 0.000 claims description 2
- WJQPUGJIYZEUSG-UHFFFAOYSA-N 5-[[4-[2-[(4,5-diphenyl-1h-imidazol-2-yl)sulfanyl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCCSC1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 WJQPUGJIYZEUSG-UHFFFAOYSA-N 0.000 claims description 2
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 2
- QXMCIBKVNSUCAT-UHFFFAOYSA-N O=C1NC(=O)C(CCCSc2nc(c([nH]2)-c2ccccc2)-c2ccccc2)S1 Chemical compound O=C1NC(=O)C(CCCSc2nc(c([nH]2)-c2ccccc2)-c2ccccc2)S1 QXMCIBKVNSUCAT-UHFFFAOYSA-N 0.000 claims description 2
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 2
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 201000006370 kidney failure Diseases 0.000 claims description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- CNLYCLKYFDZXTO-UHFFFAOYSA-N 1,3-bis[(4,5-diphenyl-1h-imidazol-2-yl)sulfanyl]-n-pentoxypropan-2-imine Chemical compound N=1C(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)NC=1SCC(=NOCCCCC)CSC(N1)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 CNLYCLKYFDZXTO-UHFFFAOYSA-N 0.000 claims 1
- IZAJXBSZYPAWGL-UHFFFAOYSA-N 1-[5-[(4,5-diphenyl-1H-imidazol-2-yl)sulfanyl]pentyl]imidazo[1,2-b]pyrazole Chemical compound C(CCSc1nc(c([nH]1)-c1ccccc1)-c1ccccc1)CCn1ccn2nccc12 IZAJXBSZYPAWGL-UHFFFAOYSA-N 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
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- 230000002401 inhibitory effect Effects 0.000 description 8
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- GMTAWLUJHGIUPU-UHFFFAOYSA-N 4,5-diphenyl-1,3-dihydroimidazole-2-thione Chemical compound N1C(S)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 GMTAWLUJHGIUPU-UHFFFAOYSA-N 0.000 description 7
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- 238000001727 in vivo Methods 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
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- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 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
- 229920001206 natural gum Polymers 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- MQNAOOIFODUDES-UHFFFAOYSA-N o-decylhydroxylamine Chemical compound CCCCCCCCCCON MQNAOOIFODUDES-UHFFFAOYSA-N 0.000 description 1
- HUOMXZJYQCOGJG-UHFFFAOYSA-N o-pentylhydroxylamine;hydrochloride Chemical compound Cl.CCCCCON HUOMXZJYQCOGJG-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- NOQXXYIGRPAZJC-UHFFFAOYSA-N oxiran-2-ylmethyl 4-methylbenzenesulfonate Chemical class C1=CC(C)=CC=C1S(=O)(=O)OCC1OC1 NOQXXYIGRPAZJC-UHFFFAOYSA-N 0.000 description 1
- 210000001819 pancreatic juice Anatomy 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003870 salicylic acids Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—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 chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur 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
- C07D417/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI93A2468 | 1993-11-22 | ||
| IT93MI002468A IT1265209B1 (it) | 1993-11-22 | 1993-11-22 | Difenilimidazoli utili nel trattamento di dislipidemia, arteriosclerosi e malattie coronariche procedimento per la loro |
| PCT/EP1994/003684 WO1995014673A1 (en) | 1993-11-22 | 1994-11-09 | 4,5-diphenylimidazole derivatives, their preparation and their use as acyl coenzyme a: cholesterol-0-acyl-transferase (acat) inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU8061894A true AU8061894A (en) | 1995-06-13 |
Family
ID=11367238
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU80618/94A Abandoned AU8061894A (en) | 1993-11-22 | 1994-11-09 | 4,5-diphenylimidazole derivatives, their preparation and their use as acyl coenzyme A: cholesterol-0-acyl-transferase (ACAT) inhibitor |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0680472A1 (it) |
| JP (1) | JPH08506122A (it) |
| AU (1) | AU8061894A (it) |
| CA (1) | CA2154475A1 (it) |
| IT (1) | IT1265209B1 (it) |
| WO (1) | WO1995014673A1 (it) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000029376A1 (fr) * | 1998-11-17 | 2000-05-25 | Kyowa Hakko Kogyo Co., Ltd. | Composes heteroarylthio et medicaments contre le cancer contenant lesdits composes |
| JPWO2004007464A1 (ja) * | 2002-07-10 | 2005-11-10 | 住友製薬株式会社 | イミダゾール誘導体 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4188397A (en) * | 1978-09-22 | 1980-02-12 | Smithkline Corporation | 2,2-Alkyldiylbis(thio)bis(imidazoles) |
| US4716175A (en) * | 1987-02-24 | 1987-12-29 | Warner-Lambert Company | Saturated fatty acid amides as inhibitors of acyl-CoA:cholesterol acyltransferase |
| IL96619A0 (en) * | 1989-12-11 | 1991-09-16 | Rhone Poulenc Sante | Imidazole derivatives,process for their preparation and pharmaceutical compositions containing them |
| JPH05502235A (ja) * | 1989-12-12 | 1993-04-22 | ローン―プーラン・サント | イミダゾール類 |
| MX9203711A (es) * | 1990-01-12 | 1992-07-01 | Rhone Poulenc Rorer Sa | Derivados de imidazol y composiciones farmaceuticas que los contienen. |
| GB9005966D0 (en) * | 1990-03-16 | 1990-05-09 | May & Baker Ltd | New compositions of matter |
| KR930701436A (ko) * | 1990-07-03 | 1993-06-11 | 오노다 마사아이 | 비스헤테로환 화합물 |
| IT1248528B (it) * | 1991-06-21 | 1995-01-19 | Pierrel Spa | Derivati di eteri e tioeteri (etero) aromatici aventi attivita` antiiperlipidemica, procedimento per la loro preparazione e composizioni farmaceutiche che li contengono. |
| GB9115190D0 (en) * | 1991-07-12 | 1991-08-28 | Rhone Poulenc Rorer Ltd | New compositions of matter |
| CA2085844A1 (en) * | 1991-12-27 | 1993-06-28 | Nobuyuki Hamanaka | Fused benzeneoxyacetic acid derivatives |
| US5364875A (en) * | 1992-05-11 | 1994-11-15 | The Du Pont Merck Pharmaceutical Company | Imidazoles linked to bicyclic heterocyclic groups for the treatment of atherosclerosis |
| US5310748A (en) * | 1992-05-11 | 1994-05-10 | The Du Pont Merck Pharmaceutical Company | Imidazoles for the treatment of atherosclerosis |
-
1993
- 1993-11-22 IT IT93MI002468A patent/IT1265209B1/it active IP Right Grant
-
1994
- 1994-11-09 EP EP94931591A patent/EP0680472A1/en not_active Withdrawn
- 1994-11-09 WO PCT/EP1994/003684 patent/WO1995014673A1/en not_active Application Discontinuation
- 1994-11-09 CA CA002154475A patent/CA2154475A1/en not_active Abandoned
- 1994-11-09 AU AU80618/94A patent/AU8061894A/en not_active Abandoned
- 1994-11-09 JP JP7514784A patent/JPH08506122A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2154475A1 (en) | 1995-06-01 |
| WO1995014673A1 (en) | 1995-06-01 |
| EP0680472A1 (en) | 1995-11-08 |
| JPH08506122A (ja) | 1996-07-02 |
| ITMI932468A0 (it) | 1993-11-22 |
| IT1265209B1 (it) | 1996-10-31 |
| ITMI932468A1 (it) | 1995-05-22 |
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