CA2098122C - Anti-atherosclerotic aryl compounds - Google Patents
Anti-atherosclerotic aryl compounds Download PDFInfo
- Publication number
- CA2098122C CA2098122C CA002098122A CA2098122A CA2098122C CA 2098122 C CA2098122 C CA 2098122C CA 002098122 A CA002098122 A CA 002098122A CA 2098122 A CA2098122 A CA 2098122A CA 2098122 C CA2098122 C CA 2098122C
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- CA
- Canada
- Prior art keywords
- alkyl
- compound
- formula
- alkoxy
- atoms
- 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.)
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- 125000003118 aryl group Chemical group 0.000 title claims abstract description 15
- 230000000879 anti-atherosclerotic effect Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- -1 C1-8 al-kyl Chemical group 0.000 claims abstract description 18
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 16
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 14
- 125000004429 atom Chemical group 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 238000011321 prophylaxis Methods 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 150000002367 halogens Chemical class 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 239000004721 Polyphenylene oxide Substances 0.000 claims abstract description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 9
- 229920000570 polyether Polymers 0.000 claims abstract description 9
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 8
- 125000004001 thioalkyl group Chemical group 0.000 claims abstract description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 7
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims abstract description 6
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 6
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 6
- 125000005111 carboxyalkoxy group Chemical group 0.000 claims abstract description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229920001774 Perfluoroether Polymers 0.000 claims abstract description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000005864 Sulphur Substances 0.000 claims abstract description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 239000011737 fluorine Substances 0.000 claims abstract description 3
- 125000004475 heteroaralkyl group Chemical group 0.000 claims abstract description 3
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 3
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims abstract description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract 5
- 150000003839 salts Chemical class 0.000 claims description 25
- 239000002775 capsule Substances 0.000 claims description 11
- 239000003112 inhibitor Substances 0.000 claims description 7
- 229940125753 fibrate Drugs 0.000 claims description 6
- 150000002431 hydrogen Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- JICHBSZAPUJPCE-UHFFFAOYSA-N 2-[4-[[(2,4-dimethoxyphenyl)carbamoyl-(3,3-dimethylbutyl)amino]methyl]phenoxy]-2-methylpropanoic acid Chemical compound COC1=CC(OC)=CC=C1NC(=O)N(CCC(C)(C)C)CC1=CC=C(OC(C)(C)C(O)=O)C=C1 JICHBSZAPUJPCE-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- BZPYOMQCTNFFHL-UHFFFAOYSA-N 2-[4-[2-[(2,4-difluorophenyl)carbamoyl-heptylamino]ethyl]phenoxy]-2-methylpropanoic acid Chemical compound C=1C=C(F)C=C(F)C=1NC(=O)N(CCCCCCC)CCC1=CC=C(OC(C)(C)C(O)=O)C=C1 BZPYOMQCTNFFHL-UHFFFAOYSA-N 0.000 claims 1
- WCQRJDARKQXJQF-UHFFFAOYSA-N 2-[4-[2-[(2,4-dimethoxyphenyl)carbamoyl-heptylamino]ethyl]phenoxy]-2-methylpropanoic acid Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=O)N(CCCCCCC)CCC1=CC=C(OC(C)(C)C(O)=O)C=C1 WCQRJDARKQXJQF-UHFFFAOYSA-N 0.000 claims 1
- XLIFANQXPBOUQP-UHFFFAOYSA-N 2-[4-[[(2,4-dimethoxyphenyl)carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoic acid Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(O)=O)C=C1 XLIFANQXPBOUQP-UHFFFAOYSA-N 0.000 claims 1
- PPOICKOOCXRMRS-UHFFFAOYSA-N 2-[4-[[heptyl-[(2,4,6-trichlorophenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoic acid Chemical compound ClC=1C=C(Cl)C=C(Cl)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(O)=O)C=C1 PPOICKOOCXRMRS-UHFFFAOYSA-N 0.000 claims 1
- JEVWGQNNEQLCNE-UHFFFAOYSA-N 3-(2,4-dimethoxyphenyl)-1-heptyl-1-[[4-(1-hydroxypropan-2-yloxy)phenyl]methyl]urea Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)CO)C=C1 JEVWGQNNEQLCNE-UHFFFAOYSA-N 0.000 claims 1
- RDEZSFIYWZQJFU-UHFFFAOYSA-N 3-(2,4-dimethylphenyl)-1-heptyl-1-[[4-(5-hydroxy-4,4-dimethylpentoxy)phenyl]methyl]urea Chemical compound C=1C=C(C)C=C(C)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OCCCC(C)(C)CO)C=C1 RDEZSFIYWZQJFU-UHFFFAOYSA-N 0.000 claims 1
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 abstract description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 abstract description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract description 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 abstract 1
- 239000003921 oil Substances 0.000 description 66
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- 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 28
- 239000000047 product Substances 0.000 description 27
- 239000004480 active ingredient Substances 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 20
- 238000009472 formulation Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 235000012000 cholesterol Nutrition 0.000 description 14
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 235000005911 diet Nutrition 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
- 108010023302 HDL Cholesterol Proteins 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000004202 carbamide Substances 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229940074076 glycerol formal Drugs 0.000 description 4
- 230000000055 hyoplipidemic effect Effects 0.000 description 4
- 230000000871 hypocholesterolemic effect Effects 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 229940069328 povidone Drugs 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 230000004141 reverse cholesterol transport Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
- WRAZHLRMDRTLOZ-UHFFFAOYSA-N 1-isocyanato-2,4-dimethoxybenzene Chemical compound COC1=CC=C(N=C=O)C(OC)=C1 WRAZHLRMDRTLOZ-UHFFFAOYSA-N 0.000 description 2
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 2
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 239000004147 Sorbitan trioleate Substances 0.000 description 2
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
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- 238000010241 blood sampling Methods 0.000 description 2
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 210000001589 microsome Anatomy 0.000 description 2
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- XDUHQPOXLUAVEE-BPMMELMSSA-N oleoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCC\C=C/CCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 XDUHQPOXLUAVEE-BPMMELMSSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
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- 230000000699 topical effect Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
- 229940029284 trichlorofluoromethane Drugs 0.000 description 2
- 229960003732 tyramine Drugs 0.000 description 2
- 229940070710 valerate Drugs 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
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- 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
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- 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
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- 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
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- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/30—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
- C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Anti-Oxidant Or Stabilizer Compositions (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909027023A GB9027023D0 (en) | 1990-12-12 | 1990-12-12 | Anti-atherosclerotic aryl compounds |
| GB9027023.2 | 1990-12-12 | ||
| PCT/GB1991/002195 WO1992010468A1 (en) | 1990-12-12 | 1991-12-11 | Anti-atherosclerotic aryl compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2098122A1 CA2098122A1 (en) | 1992-06-13 |
| CA2098122C true CA2098122C (en) | 2003-09-23 |
Family
ID=10686924
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002098122A Expired - Fee Related CA2098122C (en) | 1990-12-12 | 1991-12-11 | Anti-atherosclerotic aryl compounds |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5658944A (enExample) |
| EP (1) | EP0639178B1 (enExample) |
| JP (1) | JP2951402B2 (enExample) |
| KR (1) | KR930703246A (enExample) |
| AT (1) | ATE157651T1 (enExample) |
| AU (1) | AU647859B2 (enExample) |
| CA (1) | CA2098122C (enExample) |
| DE (1) | DE69127556D1 (enExample) |
| GB (1) | GB9027023D0 (enExample) |
| HU (1) | HUT64514A (enExample) |
| IE (1) | IE914304A1 (enExample) |
| IL (1) | IL100331A (enExample) |
| NZ (1) | NZ240935A (enExample) |
| TW (1) | TW275065B (enExample) |
| WO (1) | WO1992010468A1 (enExample) |
| ZA (1) | ZA919773B (enExample) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4401893A1 (de) * | 1994-01-24 | 1995-07-27 | Bayer Ag | Substituierte Arylharnstoffe |
| SE9401353D0 (sv) * | 1994-04-21 | 1994-04-21 | Pharmacia Ab | Novel antitumour compounds with antimitotic activity |
| AR002945A1 (es) * | 1994-11-15 | 1998-05-27 | Bayer Corp | Acidos 4-biarilbutirico o 5-biarilpentanoico sustituidos y sus derivados como inhibidores de las metaloproteasas de matriz, composicion que los contiene, y metodos para la preparacion de dichos compuestos |
| DE4443891A1 (de) * | 1994-12-09 | 1996-06-13 | Bayer Ag | Heterocyclisch substituierte Oxy-phenyl-(phenyl)glycinolamide |
| GB9606805D0 (en) * | 1996-03-30 | 1996-06-05 | Glaxo Wellcome Inc | Medicaments |
| US5866609A (en) * | 1996-08-09 | 1999-02-02 | Ss Pharmaceutical Co., Ltd. | Substituted vinylurea derivatives and medicine containing the same |
| BR0010139A (pt) * | 1999-04-28 | 2004-03-02 | Reddy Research Foundation | Heterociclos bicìclicos substituìdos, processo para seu preparo e seu uso como agentes anti-obesidade e hipocolesterolêmico |
| ATE542805T1 (de) * | 2000-08-11 | 2012-02-15 | Nippon Chemiphar Co | Ppar-delta aktivatoren |
| WO2002046176A1 (en) * | 2000-12-05 | 2002-06-13 | Nippon Chemiphar Co., Ltd. | Ppar (peroxisome proliferator activated receptor) activators |
| EP1360172A1 (en) | 2001-02-15 | 2003-11-12 | Pfizer Products Inc. | Ppar agonists |
| EP1372632A1 (en) * | 2001-02-15 | 2004-01-02 | Pfizer Products Inc. | Proliferative activator receptor (ppar) compounds |
| US6548538B2 (en) * | 2001-05-22 | 2003-04-15 | Bayer Aktiengesellschaft | Propionic acid derivatives |
| US20030191144A1 (en) * | 2001-06-12 | 2003-10-09 | Active Pass Pharmaceuticals, Inc. | Compounds, compositions and methods for modulating beta-amyloid production |
| US20030125338A1 (en) * | 2001-06-12 | 2003-07-03 | Active Pass Pharmaceuticals, Inc. | Compounds, compositions and methods for modulating beta-amyloid production |
| BRPI0211844B8 (pt) | 2001-08-10 | 2021-05-25 | Nippon Chemiphar Co | composto de ácido fenóxi-acético ou um de seus sais farmaceuticamente aceitáveis, e, composição farmacêutica |
| ES2326411T3 (es) | 2001-10-12 | 2009-10-09 | Nippon Chemiphar Co., Ltd. | Activador del receptor delta activado por proliferadores de peroxisomas. |
| US7015345B2 (en) * | 2002-02-21 | 2006-03-21 | Asahi Kasei Pharma Corporation | Propionic acid derivatives |
| BR0311834A (pt) | 2002-06-19 | 2005-04-12 | Lilly Co Eli | Composto, composição farmacêutica, métodos para mudular um receptor ativado por proliferador de peroxisoma, para tratar e prevenir diabetes mellitus em um mamìfero e para tratar sìndrome x em um mamìfero, e, uso de um composto ou seu sal farmaceuticamente aceitável |
| EP1388352A1 (en) | 2002-08-08 | 2004-02-11 | Laboratoires Fournier S.A. | Use of a ppar-alpha agonist to treat patients suffering from weight gain associated with a ppar-gamma agonist treatment |
| EA009554B1 (ru) | 2002-10-21 | 2008-02-28 | Янссен Фармацевтика Н.В. | Замещённые тетралины и инданы и их применение |
| EP1567493B1 (en) | 2002-11-26 | 2009-03-18 | Pfizer Products Inc. | Phenyl substituted piperidine compounds for use as ppar activators |
| KR20050100615A (ko) | 2003-01-14 | 2005-10-19 | 싸이토키네틱스, 인코포레이티드 | 화합물, 조성물 및 방법 |
| US6987118B2 (en) | 2003-05-21 | 2006-01-17 | Pfizer Inc. | Tetrahydroisoquinoline derivatives as PPAR-alpha activators |
| CA2570999C (en) | 2004-06-17 | 2014-01-07 | Cytokinetics, Inc. | Compounds, compositions and methods |
| US7538223B2 (en) | 2005-08-04 | 2009-05-26 | Cytokinetics, Inc. | Compounds, compositions and methods |
| TW200808321A (en) | 2005-12-15 | 2008-02-16 | Cytokinetics Inc | Certain chemical entities, compositions and methods |
| US7825120B2 (en) | 2005-12-15 | 2010-11-02 | Cytokinetics, Inc. | Certain substituted ((piperazin-1-ylmethyl)benzyl)ureas |
| EP1959962A2 (en) | 2005-12-16 | 2008-08-27 | Cytokinetics, Inc. | Certain chemical entities, compositions, and methods |
| US7989455B2 (en) | 2005-12-19 | 2011-08-02 | Cytokinetics, Inc. | Compounds, compositions and methods |
| US8404726B2 (en) | 2006-04-18 | 2013-03-26 | Nippon Chemiphar Co. Ltd. | Activating agent for peroxisome proliferator activated receptor δ |
| BRPI0911197A2 (pt) | 2008-04-15 | 2015-10-13 | Nippon Chemiphar Co | composto, ativador de receptor ativado pelo proliferador de peroxissoma, e, medicamento para o tratamento e /ou profilaxia de uma doença. |
| KR20140099546A (ko) | 2012-01-10 | 2014-08-12 | 일라이 릴리 앤드 캄파니 | 류코트리엔 b4 길항제 화합물 |
| WO2013169648A1 (en) | 2012-05-07 | 2013-11-14 | Novartis Ag | Pharmaceutical combinations comprising a dgat1 inhibtor and a triglyceride lowering drug |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2614045A1 (de) * | 1976-04-01 | 1977-10-06 | Boehringer Mannheim Gmbh | Neue phenoxyalkylcarbonsaeuren und verfahren zur herstellung derselben |
| US4397868A (en) * | 1982-01-26 | 1983-08-09 | American Cyanamid Company | Method of treating atherosclerosis with trisubstituted ureas |
| US4387106A (en) * | 1982-01-26 | 1983-06-07 | American Cyanamid Company | Method of treating atherosclerosis with di(aralkyl)ureas and di(aralkyl)thioureas |
| US4623662A (en) * | 1985-05-23 | 1986-11-18 | American Cyanamid Company | Antiatherosclerotic ureas and thioureas |
| JPH02503797A (ja) * | 1987-06-15 | 1990-11-08 | ラレザリ、イラジ | 脂質の減少、酸素に対するヘモグロビンの親和力の修正ならびに血小板凝集の抑制を行うための化合物、組成物および方法 |
| US4921997A (en) * | 1988-06-15 | 1990-05-01 | Montefiore Medical Center | Method of synthesis and novel compounds for pharmaceutical uses |
| GB8827152D0 (en) * | 1988-11-21 | 1988-12-29 | Wellcome Found | Anti-atherosclerotic diaryl compounds |
-
1990
- 1990-12-12 GB GB909027023A patent/GB9027023D0/en active Pending
-
1991
- 1991-12-11 KR KR1019930701756A patent/KR930703246A/ko not_active Withdrawn
- 1991-12-11 CA CA002098122A patent/CA2098122C/en not_active Expired - Fee Related
- 1991-12-11 AU AU90560/91A patent/AU647859B2/en not_active Ceased
- 1991-12-11 JP JP4501716A patent/JP2951402B2/ja not_active Expired - Lifetime
- 1991-12-11 NZ NZ240935A patent/NZ240935A/en unknown
- 1991-12-11 ZA ZA919773A patent/ZA919773B/xx unknown
- 1991-12-11 IL IL10033191A patent/IL100331A/en not_active IP Right Cessation
- 1991-12-11 IE IE430491A patent/IE914304A1/en unknown
- 1991-12-11 DE DE69127556T patent/DE69127556D1/de not_active Expired - Lifetime
- 1991-12-11 WO PCT/GB1991/002195 patent/WO1992010468A1/en not_active Ceased
- 1991-12-11 EP EP92900716A patent/EP0639178B1/en not_active Expired - Lifetime
- 1991-12-11 AT AT92900716T patent/ATE157651T1/de not_active IP Right Cessation
- 1991-12-11 HU HU9301709A patent/HUT64514A/hu unknown
-
1992
- 1992-01-24 TW TW081100492A patent/TW275065B/zh active
-
1995
- 1995-04-14 US US08/421,997 patent/US5658944A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06507151A (ja) | 1994-08-11 |
| IL100331A0 (en) | 1992-09-06 |
| HU9301709D0 (en) | 1993-09-28 |
| WO1992010468A1 (en) | 1992-06-25 |
| AU9056091A (en) | 1992-07-08 |
| AU647859B2 (en) | 1994-03-31 |
| US5658944A (en) | 1997-08-19 |
| GB9027023D0 (en) | 1991-01-30 |
| NZ240935A (en) | 1994-11-25 |
| ZA919773B (en) | 1993-06-11 |
| KR930703246A (ko) | 1993-11-29 |
| HUT64514A (en) | 1994-01-28 |
| IE914304A1 (en) | 1992-06-17 |
| TW275065B (enExample) | 1996-05-01 |
| ATE157651T1 (de) | 1997-09-15 |
| IL100331A (en) | 1996-09-12 |
| DE69127556D1 (de) | 1997-10-09 |
| EP0639178B1 (en) | 1997-09-03 |
| EP0639178A1 (en) | 1995-02-22 |
| CA2098122A1 (en) | 1992-06-13 |
| JP2951402B2 (ja) | 1999-09-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |