| 摘要 |
1412311 α-Amino arylacetamidocephalosporin compounds BRISTOL-MYERS CO 26 Feb 1973 [25 Feb 1972 (2) 28 Feb 1972 16 March 1972 12 June 1972] 9346/73 Heading C2C Novel cephalosporin compounds having the D-configuration in the 7-side chain and having the general Formula (I) and base salts and acid addition salts thereof, wherein Ar is phenyl, 2-thienyl or 3-thienyl; R is hydrogen, pivaloyloxymethyl, acetoxymethyl, methoxymethyl, acetonyl or phenacyl; and Z is one of the following groups: are prepared by N-acylating a corresponding 7- amino cephalosporin compound or a salt or easily hydrolysed ester thereof, with an acid of Formula (III): having the D-configuration, wherein Ar is as defined above and B is an amino-protecting group, or with an N-acylating functional derivative of said acid, and then removing said blocking group and, if necessary, hydrolysing said ester group, and, if desired, either converting the product wherein R is H to the corresponding compound wherein R is one of the specified esterifying groups or vice versa. The acylating agent (III) may be the acid chloride hydrochloride, the protonation of the amino group serving as the protecting group B, or the mixed acid anhydride (e.g. with ethyl chloroformate) wherein the amino group is protected by enamine formation with a #- diketone (e.g. methyl acetoacetate). The starting 7-aminocephalosporin compounds are prepared by reacting either a 7-amino-3-acetoxymethyl cephalosporanic acid or ester thereof with an appropriate heterocyclic thiocarboxylic acid, or by corresponding reaction of a 7-acylamido-3-acetoxymethyl cephalosporanic acid or ester followed by an N-deacylation treatment to give the 7-amino analogue. The inventive cephalosporin compounds I and their non-toxic salts may be made up with a pharmaceutical diluent or carrier into pharmaceutical compositions having antibacterial activity. Examples are given for preparation of the following starting materials: 3-methylisoxazole- 5 - thiocarboxylic acid; 1 - methyl - 4 - carboxyl- 1,2,3 - triazole; 1 - methyl - 1,2,3 - triazole - 4- carbonyl chloride; 1-methyl-1,2,3-triazole-4-thiocarboxylic acid potassium salt; 1,2,3-thiadiazole- 5 - carboxylic acid; 1,2,3 - thiadiazole - 5 - carbonyl chloride; 1,2,3 - thiadiazole - 5 - thiocarboxylic acid potassium salt; isothiazole - 5- thiocarboxylic acid; isothiazole - 3 - carboxylic acid chloride; potassium isothiazole-3-thiocarboxylate, isothiazole - 4 - carboxylic acid chloride; potassium isothiazole - 4 - thiocarboxylate; and 1,2,5-thiadiazole-3-carboxylic thioacid. |
