| 摘要 |
1,164,457. Esters of 6-aminopenicillanic acid; penicillins; cephalosporins. BRISTOL-MYERS CO. 22 July, 1966 [22 July, 1965], No. 33038/66. Headings C2A and C2C, The invention relates to activated esters of 6-aminopenicillanic acid of formula wherein when W represents H, Z represents C 1 -C 10 alkanoyl, aroyl, substituted aroyl, N- phthalimido, N-succinimido, N-saccharino, N,N- dialkylcarbamoyl, cyano, C 1 -C 10 alkoxy, C 1 - C 10 alkylthio, aryloxy, carbalkoxy, carbobenzoxy, carbamoyl, benzyloxy, carbophenoxy, carbo-t.-butoxy or C 1 -C 10 alkylsulphonyl; when W represents carbalkoxy, Z represents carbalkoxy; when W represents phenyl, Z represents benzoyl or cyano; when W represents C 1 -C 10 alkyl, Z represents C 1 -C 10 alkanoyl; or W and Z together represent 2-oxocycloalkyl containing 4 to 8 C atoms; and salts with inorganic and organic acids. The esters are prepared by (A) deacylating the corresponding activated ester of penicillin with an amidase, e.g. of E. coli or Arthrobacter viscosus; (B) reacting a salt of 6-aminopenicillanic acid in an inert solvent with an active halide of formula wherein W and Z have the above meanings and X is Cl or Br; (C) treating an activated ester made from 6-(N-tritylamino) penicillanic acid and an alcohol of formula wherein W and Z have the above meanings, with p-toluenesulphonic acid monohydrate. Penicillins are prepared by reacting an ester of 6-aminopenicillanic acid as above with an acylating agent for a primary amine and thereafter removing the ester group from the N- acylated 6-aminopenicillanic acid ester by means of (A) ultraviolet light or (B) sodium thiophenoxide. The invention also comprises α-guanidino- α-thienyl acetamido penicillanic acids and salts of Formula IV D ( - ) α - (2 - Thienyl) - α - guanidinoacetic acid is prepared by treating D ( - ) - α - (2 - thienyl) glycine with o-methyl pseudo-urea sulphate previously treated with sodium methylate in methanol. D (- ) - α - Ureidophenylacetic acid is prepared by treating D ( - ) - α - aminophenylacetic acid with aqueous potassium cyanate followed by acidification with HCl. 7 - Amino - ceph - 3 - em - 3 - yl methyl pyridinium 4:-carboxylate is prepared from N-phthalimidomethyl - 6 - aminopenicillanate by reaction scheme A. Pharmaceutical compositions comprise an α-guanidino-α-thienyl penicillin (IV) or other penicillin as above and a carrier. They may be used for the treatment of mastitis and other infectious diseases in cattle. They may be incorporated in animal feeds and may be used generally as an antibacterial agent. Reference has been directed by the Comptroller to Specification 1,025,425. |
