| 摘要 |
<p>1,174,335. 7-α-amino-3-methyl cephalosporin analogues. ELI LILLEY & CO. 7 March, 1967, No. 10722/67. Heading C2A. The invention relates to 7-(α-aminophenylacetamido) - 3 - methyl - #<SP>3</SP> - cephem - 4 - carboxylic acids of Formula I wherein R is phenyl or phenyl substituted with halo, OH, C 1-4 alkyl, NO 2 , NH 2 , C 1-4 alkanoyl, trifluoromethyl, C 1-4 alkoxy or C 1-4 alkylmercapto; or a salt thereof with a pharmaceutically acceptable cation or a pharmaceutically acceptable acid. The compounds are prepared by (A) subjecting to hydrogenolysis a compound of formula wherein R<SP>1</SP> is H or R-CHNH 2 .CO- wherein R has the above meaning, and when R<SP>1</SP> is H, acylating the 7-amino-3-methyl-#<SP>3</SP>-cephem-4- carboxylic acid thus obtained in a conventional manner with an acylating agent comprising the radical R-CHNH 2 CO-; or (B) heating under acid conditions a penicillin sulphoxide of formula wherein R is as defined above and wherein the NH 2 group in the 6-position and the carboxylate group in the 3-position are protected in a conventional manner, and thereafter removing the protective group. The hydrogenolysis of (A) is by hydrogen and a noble metal catalyst, e.g. palladium on BaSO 4 , at pH 7À5 to 9À0. The heating step of (B) is at 100-175‹ C. in the presence of a strong acid. Typical compounds are 7 - (α- aminophenylacetamido)- 3 - methyl- #<SP>3</SP> - cephem - 4 - carboxylic acid and 7 - (α- amino - m - chlorophenylacetamido) - 3 - methyl - #<SP>3</SP> - cephem - 4 - carboxylic acid. The protected penicillin is converted to the sulphoxide by treatment with an oxidizing agent such as hydrogen peroxide in acetic acid, metaperiodic acid in hydrochloric acid or perbenzoic acid. Pharmaceutical compositions having antibacterial activity comprise an excipient and a 7-α-aminobenzyl-3-methyl cephalosporin analogue of Formula I.</p> |
