ALPHA-AMINO-ARYLACETAMIDO CEPHALOSPORIN COMPOUNDS

摘要

1492095α-Amino-arylacetamido cephalosporins BRISTOL-MYERS CO 25 July 1975 [26 July 1974 29 July 1974] 31210/75 Heading C2C Novel compounds having the D-configuration in the 7-sidechain and the formula wherein Ar is phenyl, 2- or 3-thienyl; R is hydrogen, pivaloyloxymethyl, acetoxymethyl, methoxymethyl, acetonyl or phenacyl; and R1 is 2-thiazolyl or 5-methyl-2-thiazolyl or 3- methyl-1,2,5-oxadiazol-4-yl; or a pharmaceutically acceptable salt thereof, may be obtained by (a) reacting a compound of the formula or an easily cleavable ester or salt thereof, with a heteroaromatic thiolcarboxylic acid of the formula R1COSH, or (b) reacting a compound of the formula or an easily cleavable ester or salt thereof with an acid of the formula or an acylating derivative thereof, wherein B is an amino-protecting group, and removing said group B to produce I or an easily cleavable ester or pharmaceutically acceptable salt thereof and, if desired, in (b) either before or after removal of B (i) converting the product to an easily cleavable ester or pharmaceutically acceptable salt, or (ii) converting the product in the form of an ester or salt to the acid or another salt. Intermediates are described as follows: 2- carboxythiazole is reacted with oxalyl chloride to form the acid chloride then with sodium sulphydrate trihydrate and then dicyclohexylamine to form thiazole-2-thiocarboxylic acid dicyclohexylamine salt. The latter is converted to free acid and reacted with 7-aminocephalosporanic acid to form 7-amino-3-(2-thiazolyl)- carbonylthiomethyl - 3 - cephem - 4 - carboxylic acid, which is then converted to the respective pivaloyloxymethyl, acetoxymethyl, methoxymethyl, acetonyl and phenacyl ester. 5-Methylthiazole - 2 - thiocarboxylic acid dicyclohexylamine salt is similarly prepared and converted to 7 - amino - 3 - (5 - methylthiazol - 2 - yl) carbonylthiomethyl-3-cephem-4-carboxylic acid and esters as above. 3-Methyl-1,2,5-oxadiazole-4- thiolcarboxylic acid is similarly obtained and converted to 7-amino-(3-methyl-1,2,5-oxadiazol- 4-yl) carbonylthiomethyl - 3 - cephem-4-carboxylic acid and esters corresponding to those above. Pharmaceutical and veterinary compositions comprise compounds of Formula I above, and a pharmaceutically acceptable carrier or diluent especially in forms suitable for administration orally or parenterally, including animal or poultry feed.