| 摘要 |
1496307 Thiophene derivatives RICHARDSON-MERRELL Inc 3 May 1976 [16 June 1975] 17956/76 Heading C2C Novel compounds I in which Y is O or S, R is C 10-20 alkyl or C 10-20 alkenyl containing 1 to 4 double bonds, R 1 is H, C 1-6 alkyl, benzyl, phenethyl, pyridylmethyl, -(CH 2 ) n -NR 2 R 3 , where n is 2 or 3, R 2 is H and R 3 is C 1-4 alkyl-carbonyl, or each of R 2 and R 3 is C 1-4 alkyl or R 2 and R 3 together with the nitrogen atom represent pyrrolidino, piperidino, morpholino or piperazino, or R 1 is the group of Formula A where the sum of m and p is 3 to 5 and R 4 is C 1-4 alkyl, and pharmaceutically acceptable salts thereof, are prepared by reacting an R-Y- substituted thiophene methyl ketone with magnesium methyl carbonate followed by treating the resulting complex with an acid and water to give a compound I in which R 1 is H, if desired esterifying this to form esters of Formula I, and, if desired, transesterifying a resulting ester. Compounds I where R 1 is other than H may also be formed by condensing a compound VII in which X is halogen, 1-imidazolyl or C 1-4 alkyl, with an ester of acetoacetic acid followed by alkaline hydrolysis of the resulting thenoylacetoacetate, or with an ester of acetic acid. These compounds may also be obtained by acylation of compounds VII in which X is halogen or 1-imidazolyl, with a magnesium complex of malonic acid mono-ester. R-Y-substituted thiophene methyl ketones are prepared by (a) reaction of methyl magnesium bromide with the imidazolide derivative of an R-Y-substituted thiophene carboxylic acid (itself prepared from a halo-substituted thiophene carboxylic acid or an R-Y-substituted thiophene), or (b) acylationofan R-Y-substituted thiophene, or (c) treatment of the corresponding acid with methyl lithium. Compounds VII in which X is halogen are prepared from the corresponding acids while compounds VII in which X is 1-imidazolyl are prepared from the corresponding acids or acid chlorides. 2-R-O-substituted thiophenes are prepared by reacting 3-thiolen-2-one with a suitable hydrocarbylating agent. Pharmaceutical compositions having hypolipidemic activity, for oral or parenteral administration, comprise one of the above novel compounds together with a pharmaceutical carrier. |
