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
- Authority
- 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.)
- Expired - Fee Related
Links
- 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
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 150000001840 cholesterol esters Chemical class 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 210000001589 microsome Anatomy 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 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
- 238000001953 recrystallisation Methods 0.000 description 2
- 229940085605 saccharin sodium Drugs 0.000 description 2
- 238000007493 shaping process Methods 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 235000019337 sorbitan trioleate Nutrition 0.000 description 2
- 229960000391 sorbitan trioleate Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 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
- ZQPPMHVWECSIRJ-JVBZJRCZSA-N (z)-octadec-9-enoic acid Chemical compound CCCCCCCC\C=C/CCCCCCC[14C](O)=O ZQPPMHVWECSIRJ-JVBZJRCZSA-N 0.000 description 1
- KERKXVHMABMAJX-UHFFFAOYSA-N 1-heptyl-1-[[4-(1-hydroxy-2-methylpropan-2-yl)oxyphenyl]methyl]-3-(2-phenylphenyl)urea Chemical compound C=1C=CC=C(C=2C=CC=CC=2)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)CO)C=C1 KERKXVHMABMAJX-UHFFFAOYSA-N 0.000 description 1
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 1
- HNENEALJPWJWJY-UHFFFAOYSA-N 2,4-difluoro-1-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C(F)=C1 HNENEALJPWJWJY-UHFFFAOYSA-N 0.000 description 1
- RWEFQEAVUVVSTQ-UHFFFAOYSA-N 2-[4-[2-[(2,4-dimethoxyphenyl)carbamoylamino]ethyl]phenoxy]-2-methylpropanoic acid Chemical compound COC1=CC(OC)=CC=C1NC(=O)NCCC1=CC=C(OC(C)(C)C(O)=O)C=C1 RWEFQEAVUVVSTQ-UHFFFAOYSA-N 0.000 description 1
- UVPHDHVSVCRIBA-UHFFFAOYSA-N 2-[4-[2-[[2,6-di(propan-2-yl)phenyl]carbamoyl-heptylamino]ethyl]phenoxy]-2-methylpropanoic acid Chemical compound CC(C)C=1C=CC=C(C(C)C)C=1NC(=O)N(CCCCCCC)CCC1=CC=C(OC(C)(C)C(O)=O)C=C1 UVPHDHVSVCRIBA-UHFFFAOYSA-N 0.000 description 1
- FOPRYMJDSUHHGW-UHFFFAOYSA-N 2-[4-[3-[(2,4-dimethoxyphenyl)carbamoyl-heptylamino]propyl]phenoxy]-2-methylpropanoic acid Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=O)N(CCCCCCC)CCCC1=CC=C(OC(C)(C)C(O)=O)C=C1 FOPRYMJDSUHHGW-UHFFFAOYSA-N 0.000 description 1
- FNLIVWDRLSTRRU-UHFFFAOYSA-N 2-[4-[[(4-chlorophenyl)carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoic acid Chemical compound C=1C=C(Cl)C=CC=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(O)=O)C=C1 FNLIVWDRLSTRRU-UHFFFAOYSA-N 0.000 description 1
- VEVAXCOBDANRKT-UHFFFAOYSA-N 2-[4-[[heptyl-[(2-phenylphenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoic acid Chemical compound C=1C=CC=C(C=2C=CC=CC=2)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(O)=O)C=C1 VEVAXCOBDANRKT-UHFFFAOYSA-N 0.000 description 1
- UHUUCHGGRMZYAW-UHFFFAOYSA-N 3-(2,4-dimethoxyphenyl)-1-heptyl-1-[2-[4-(1-hydroxy-2-methylpropan-2-yl)oxyphenyl]ethyl]urea Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=O)N(CCCCCCC)CCC1=CC=C(OC(C)(C)CO)C=C1 UHUUCHGGRMZYAW-UHFFFAOYSA-N 0.000 description 1
- NTWODISOLKFGIA-UHFFFAOYSA-N 3-(2,4-dimethoxyphenyl)-1-heptyl-1-[[4-(1-hydroxybutan-2-yloxy)phenyl]methyl]urea Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(CC)CO)C=C1 NTWODISOLKFGIA-UHFFFAOYSA-N 0.000 description 1
- UISNLGHWBYZHIH-UHFFFAOYSA-N 5-[4-[[(2,4-dimethoxyphenyl)carbamoyl-heptylamino]methyl]phenoxy]-2,2-dimethylpentanoic acid Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OCCCC(C)(C)C(O)=O)C=C1 UISNLGHWBYZHIH-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 229920003094 Methocel™ K4M Polymers 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 1
- 108010054082 Sterol O-acyltransferase Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 229940116731 Uricosuric agent Drugs 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940089206 anhydrous dextrose Drugs 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 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 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 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 description 1
- 230000008021 deposition Effects 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- BFKGIERDPONYNV-UHFFFAOYSA-N ethyl 2-[2-[[(2,4-difluoro-6-methoxyphenyl)carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoate Chemical compound FC=1C=C(F)C=C(OC)C=1NC(=O)N(CCCCCCC)CC1=CC=CC=C1OC(C)(C)C(=O)OCC BFKGIERDPONYNV-UHFFFAOYSA-N 0.000 description 1
- VVHKMGRDYRTHQI-UHFFFAOYSA-N ethyl 2-[4-[[(2,4-dichloro-6-ethoxyphenyl)carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoate Chemical compound ClC=1C=C(Cl)C=C(OCC)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 VVHKMGRDYRTHQI-UHFFFAOYSA-N 0.000 description 1
- GGIDQXYYMOHDQP-UHFFFAOYSA-N ethyl 2-[4-[[(2,4-difluoro-6-methoxyphenyl)carbamoyl-(2-methylnonan-2-yl)amino]methyl]phenoxy]-2-methylpropanoate Chemical compound FC=1C=C(F)C=C(OC)C=1NC(=O)N(C(C)(C)CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 GGIDQXYYMOHDQP-UHFFFAOYSA-N 0.000 description 1
- RYEFGZSTINDXBU-UHFFFAOYSA-N ethyl 2-[4-[[(2-ethoxy-4,6-difluorophenyl)carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoate Chemical compound FC=1C=C(F)C=C(OCC)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 RYEFGZSTINDXBU-UHFFFAOYSA-N 0.000 description 1
- GYMXEXRQRHFITP-UHFFFAOYSA-N ethyl 2-[4-[[(3,4-dichlorophenyl)carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C=C(Cl)C(Cl)=CC=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 GYMXEXRQRHFITP-UHFFFAOYSA-N 0.000 description 1
- OZZAZXUGLOLPIG-UHFFFAOYSA-N ethyl 2-[4-[[(5-chloro-2,4-dimethoxyphenyl)carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C(Cl)=C(OC)C=C(OC)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 OZZAZXUGLOLPIG-UHFFFAOYSA-N 0.000 description 1
- RFOUOSKSLVWHGA-UHFFFAOYSA-N ethyl 2-[4-[[1,1-dimethoxyhexyl-[(2,4-dimethoxyphenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=O)N(C(OC)(OC)CCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 RFOUOSKSLVWHGA-UHFFFAOYSA-N 0.000 description 1
- DYEHXBICGFXXDY-UHFFFAOYSA-N ethyl 2-[4-[[2-(4-chlorophenyl)ethyl-[(2,4-dimethoxyphenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoate Chemical compound C1=CC(OC(C)(C)C(=O)OCC)=CC=C1CN(C(=O)NC=1C(=CC(OC)=CC=1)OC)CCC1=CC=C(Cl)C=C1 DYEHXBICGFXXDY-UHFFFAOYSA-N 0.000 description 1
- DZVXZHHNDUHORI-UHFFFAOYSA-N ethyl 2-[4-[[[2,4-dichloro-6-[[4-(2,2-dimethylpropanoyl)phenyl]methoxy]phenyl]carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoate Chemical compound ClC=1C=C(Cl)C=C(OCC=2C=CC(=CC=2)C(=O)C(C)(C)C)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 DZVXZHHNDUHORI-UHFFFAOYSA-N 0.000 description 1
- DIFYXOFJMSYSSK-UHFFFAOYSA-N ethyl 2-[4-[[[2-[(4-tert-butylphenyl)methoxy]-4-methoxyphenyl]carbamoyl-heptylamino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C=C(OC)C=C(OCC=2C=CC(=CC=2)C(C)(C)C)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 DIFYXOFJMSYSSK-UHFFFAOYSA-N 0.000 description 1
- JCQMNFAAIHLBFW-UHFFFAOYSA-N ethyl 2-[4-[[heptyl-[(2-methyl-6-propan-2-ylphenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoate Chemical compound CC=1C=CC=C(C(C)C)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 JCQMNFAAIHLBFW-UHFFFAOYSA-N 0.000 description 1
- ZEPJCQSAMQVKTI-UHFFFAOYSA-N ethyl 2-[4-[[heptyl-[(2-methylphenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C=CC=C(C)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 ZEPJCQSAMQVKTI-UHFFFAOYSA-N 0.000 description 1
- WFYOSCAQZPKCTF-UHFFFAOYSA-N ethyl 2-[4-[[heptyl-[(2-phenoxyphenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C=CC=C(OC=2C=CC=CC=2)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 WFYOSCAQZPKCTF-UHFFFAOYSA-N 0.000 description 1
- URFDESFVJFJDRT-UHFFFAOYSA-N ethyl 2-[4-[[heptyl-[(2-propan-2-ylphenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C=CC=C(C(C)C)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 URFDESFVJFJDRT-UHFFFAOYSA-N 0.000 description 1
- GVEOHMZSZQZFRZ-UHFFFAOYSA-N ethyl 2-[4-[[heptyl-[(2-propoxyphenyl)carbamoyl]amino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C=CC=C(OCCC)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 GVEOHMZSZQZFRZ-UHFFFAOYSA-N 0.000 description 1
- WZBOPNBVUWWZNV-UHFFFAOYSA-N ethyl 2-[4-[[heptyl-[[2-(trifluoromethoxy)phenyl]carbamoyl]amino]methyl]phenoxy]-2-methylpropanoate Chemical compound C=1C=CC=C(OC(F)(F)F)C=1NC(=O)N(CCCCCCC)CC1=CC=C(OC(C)(C)C(=O)OCC)C=C1 WZBOPNBVUWWZNV-UHFFFAOYSA-N 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- FXHGMKSSBGDXIY-UHFFFAOYSA-N heptanal Chemical compound CCCCCCC=O FXHGMKSSBGDXIY-UHFFFAOYSA-N 0.000 description 1
- 239000002035 hexane extract Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000010016 myocardial function Effects 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000004094 surface-active agent 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
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 239000003383 uricosuric agent Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- 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
-
- 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
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (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)
- Anti-Oxidant Or Stabilizer Compositions (AREA)
- Indole Compounds (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (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 (OSRAM) |
| EP (1) | EP0639178B1 (OSRAM) |
| JP (1) | JP2951402B2 (OSRAM) |
| KR (1) | KR930703246A (OSRAM) |
| AT (1) | ATE157651T1 (OSRAM) |
| AU (1) | AU647859B2 (OSRAM) |
| CA (1) | CA2098122C (OSRAM) |
| DE (1) | DE69127556D1 (OSRAM) |
| GB (1) | GB9027023D0 (OSRAM) |
| HU (1) | HUT64514A (OSRAM) |
| IE (1) | IE914304A1 (OSRAM) |
| IL (1) | IL100331A (OSRAM) |
| NZ (1) | NZ240935A (OSRAM) |
| TW (1) | TW275065B (OSRAM) |
| WO (1) | WO1992010468A1 (OSRAM) |
| ZA (1) | ZA919773B (OSRAM) |
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 |
| CZ20013832A3 (cs) * | 1999-04-28 | 2002-04-17 | Dr. Reddy's Research Foundation | Substituované bicyklické heterocyklické sloučeniny, způsob jejich přípravy a jejich pouľití jako antiobezitních a hypocholesterolemických činidel |
| AU2001277723A1 (en) | 2000-08-11 | 2002-02-25 | Nippon Chemiphar Co., Ltd. | Ppardelta activators |
| JPWO2002046176A1 (ja) * | 2000-12-05 | 2004-04-08 | 日本ケミファ株式会社 | ペルオキシソーム増殖剤応答性受容体の活性化剤 |
| WO2002064549A1 (en) * | 2001-02-15 | 2002-08-22 | Pfizer Products Inc. | Ppar agonists |
| CA2438492A1 (en) * | 2001-02-15 | 2002-08-22 | 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 |
| WO2002100836A2 (en) * | 2001-06-12 | 2002-12-19 | Active Pass Pharmaceuticals, Inc. | Compounds, compositions and methods for modulating beta-amyloid production |
| AU2002323776B2 (en) | 2001-08-10 | 2008-07-31 | Nippon Chemiphar Co., Ltd. | Activator for peroxisome proliferator-responsive receptor Delta |
| MXPA04003398A (es) | 2001-10-12 | 2004-11-22 | Nippon Chemiphar Co | Activador para el receptor o activado con el proliferador de peroxisoma. |
| 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 |
| HRP20050336B1 (hr) | 2002-10-21 | 2013-06-30 | Janssen Pharmaceutica N.V. | Supstituirani tetralini i indani i njihova primjena |
| PL378268A1 (pl) | 2002-11-26 | 2006-03-20 | Pfizer Products Inc. | Aktywatory PPAR |
| AU2004206860B2 (en) | 2003-01-14 | 2010-03-18 | Cytokinetics, Inc. | Compounds, compositions and methods |
| US6987118B2 (en) | 2003-05-21 | 2006-01-17 | Pfizer Inc. | Tetrahydroisoquinoline derivatives as PPAR-alpha activators |
| NZ552404A (en) | 2004-06-17 | 2010-04-30 | Cytokinetics Inc | Compounds, compositions and methods |
| US7538223B2 (en) | 2005-08-04 | 2009-05-26 | Cytokinetics, Inc. | Compounds, compositions and methods |
| US7825120B2 (en) | 2005-12-15 | 2010-11-02 | Cytokinetics, Inc. | Certain substituted ((piperazin-1-ylmethyl)benzyl)ureas |
| WO2007070683A2 (en) | 2005-12-15 | 2007-06-21 | Cytokinetics, Inc. | Certain chemical entities, compositions and methods |
| WO2007078815A2 (en) | 2005-12-16 | 2007-07-12 | Cytokinetics, Inc. | Certain chemical entities, compositions, and methods |
| WO2007078839A2 (en) | 2005-12-19 | 2007-07-12 | Cytokinetics, Inc. | Compounds, compositions and methods |
| JP5290749B2 (ja) | 2006-04-18 | 2013-09-18 | 日本ケミファ株式会社 | ペルオキシソーム増殖剤活性化受容体δの活性化剤 |
| US8648208B2 (en) | 2008-04-15 | 2014-02-11 | Nippon Chemiphar Co. Ltd. | Activating agent for peroxisome proliferator activated receptor |
| CA2857521C (en) | 2012-01-10 | 2016-03-01 | Eli Lilly And Company | Leukotriene b4 antagonist compound |
| 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 |
| AU616674B2 (en) * | 1987-06-15 | 1991-11-07 | Iraj Lalezari | Compound, composition and method for the reduction of lipids the modification of the affinity of hemoglobin for oxygen and the prevention of platelet aggregation |
| 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 DE DE69127556T patent/DE69127556D1/de not_active Expired - Lifetime
- 1991-12-11 KR KR1019930701756A patent/KR930703246A/ko not_active Withdrawn
- 1991-12-11 JP JP4501716A patent/JP2951402B2/ja not_active Expired - Lifetime
- 1991-12-11 WO PCT/GB1991/002195 patent/WO1992010468A1/en not_active Ceased
- 1991-12-11 IE IE430491A patent/IE914304A1/en unknown
- 1991-12-11 NZ NZ240935A patent/NZ240935A/en unknown
- 1991-12-11 ZA ZA919773A patent/ZA919773B/xx unknown
- 1991-12-11 CA CA002098122A patent/CA2098122C/en not_active Expired - Fee Related
- 1991-12-11 HU HU9301709A patent/HUT64514A/hu unknown
- 1991-12-11 AU AU90560/91A patent/AU647859B2/en not_active Ceased
- 1991-12-11 AT AT92900716T patent/ATE157651T1/de not_active IP Right Cessation
- 1991-12-11 IL IL10033191A patent/IL100331A/en not_active IP Right Cessation
- 1991-12-11 EP EP92900716A patent/EP0639178B1/en not_active Expired - Lifetime
-
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 |
|---|---|
| KR930703246A (ko) | 1993-11-29 |
| ATE157651T1 (de) | 1997-09-15 |
| JP2951402B2 (ja) | 1999-09-20 |
| IL100331A (en) | 1996-09-12 |
| JPH06507151A (ja) | 1994-08-11 |
| AU9056091A (en) | 1992-07-08 |
| US5658944A (en) | 1997-08-19 |
| TW275065B (OSRAM) | 1996-05-01 |
| HUT64514A (en) | 1994-01-28 |
| DE69127556D1 (de) | 1997-10-09 |
| ZA919773B (en) | 1993-06-11 |
| IL100331A0 (en) | 1992-09-06 |
| EP0639178B1 (en) | 1997-09-03 |
| CA2098122A1 (en) | 1992-06-13 |
| HU9301709D0 (en) | 1993-09-28 |
| EP0639178A1 (en) | 1995-02-22 |
| GB9027023D0 (en) | 1991-01-30 |
| AU647859B2 (en) | 1994-03-31 |
| NZ240935A (en) | 1994-11-25 |
| IE914304A1 (en) | 1992-06-17 |
| WO1992010468A1 (en) | 1992-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2098122C (en) | Anti-atherosclerotic aryl compounds | |
| US5776951A (en) | Anti-atherosclerotic diaryl compounds | |
| EP0462264B1 (fr) | Derives heterocycliques, leur procede de preparation et leur application therapeutique comme antagonistes du paf | |
| JP2005521639A (ja) | プロテアーゼ阻害薬としてのシアノアルキルアミノ誘導体 | |
| FR2562889A1 (fr) | Composes de phenethanolamine. procede pour leur preparation et compositions pharmaceutiques les comprenant | |
| FR2471968A1 (fr) | Ethers basiques, leur procede de preparation et compositions pharmaceutiques les contenant | |
| CH619932A5 (OSRAM) | ||
| JPS6212754A (ja) | Ｐａｆ合成阻害剤として有用なリン脂質類似体 | |
| FR2733750A1 (fr) | Derives de l'acide gamma-oxo-alpha-(phenylmethyl)-5,6- dihydro-4h-thieno(3,4-c)pyrrole-5-butanoique, leur preparation et leur application en therapeutique | |
| MC1770A1 (fr) | Composes heterocycliques | |
| EP0239461A1 (fr) | Dérivés de N-¬¬(hydroxy-2 phényl) (phényl) méthylène amino-2 éthyl acétamide, leur préparation et leur application en thérapeutique | |
| FR2584400A1 (fr) | Esters et amides de l'acide eicosatriynoique et leur application en pharmacie et en cosmetique | |
| US5422373A (en) | Anti-atherosclerotic aryl compounds | |
| EP0439059B1 (en) | 1-Phenylalkyl-3-phenylurea derivative | |
| FR2541275A1 (fr) | Nouveaux derives de la piperazine et leurs sels, leur procede de preparation et leur application en therapeutique | |
| US5232941A (en) | Caffeic acid derivatives and pharmaceutical compositions containing the same | |
| FR2483232A1 (fr) | Nouveaux agents anti-rhinovirus et leur procede de preparation | |
| LU81554A1 (de) | Alkylthiophenoxyalkylamines | |
| EP0143016B1 (fr) | Dérivés de 4-(3-alkynyloxy-2-hydroxy-propyl)-piperazin-1-yl-N-phényl acétamide, leur préparation et leur application en thérapeutique | |
| EP0240398A1 (fr) | Dérivés dissymétriques de l'acide 1,4-dihydropyridine-3,5-dicarboxylique, procédés de préparation et utilisation en thérapeutique | |
| CH632261A5 (fr) | Nouveaux derives du chromene et leurs procedes de preparation. | |
| LU81430A1 (fr) | Nouvelles cystamines | |
| CA1210392A (fr) | Procede pour la preparation d'amides n-substitues, et les amides ainsi obtenus | |
| EP0123605B1 (fr) | N-Cyclopropylméthyl-2 oxo-3 diparaméthoxyphenyl 5-6 as triazine, son procédé de fabrication et son utilisation en tant que médicament | |
| EP0189080A2 (en) | (1,2,4-Oxadiazol-3-YL)-arylmethanones, a process for their preparation and their use as medicaments |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |