GB1187323A - Sydnone and Sydnone Imine Derivatives of 7-Aminocephalosporanic Acids and Preparation thereof - Google Patents

Abstract

1,187,323. Cephalosporins. FUJISAWA PHARMACEUTICAL CO. Ltd. 26 June, 1967 [29 June, 1966; 2 Nov., 1966 (3); 7 Nov., 1966; 12 Nov., 1966; 18 Feb., 1967], No. 29465/67. Heading C2A. The invention comprises a sydnone and sydnone imine derivative of 7-aminocephalosporanic acid, and pharmaceutically acceptable salts thereof, of Formula I: wherein R 1 is O, imino, acylimino, C 1 -C 4 alkylcarbamoylimino, arylcarbamoylimino, C 1 -C 4 alkylthiocarbamoylimino or arylthiocarbamoylimino; R 2 is C 1 -C 4 alkyl, aryl or aryl C 1 -C 4 alkyl; R 3 is H, halogen, C 1 -C 4 alkyl, aryl or aryl C 1 -C 4 alkyl; Z is carbonyl, C 1 -C 4 alkylenecarbonyl, aryl C 1 -C 4 alkylene carbonyl or arylene C 1 -C 4 alkylene carbonyl when it is attached to the 4-position of the sydnone ring, or Z is C 1 -C 4 alkylene carbonyl, aryl C 1 -C 4 alkylene carbonyl or arylene-C 1 -C 4 alkylene carbonyl when it is attached to the 3-position of the sydnone ring; R 4 is acetoxy, azido, pyridinium, arylamino, N-C 1 -C 4 alkylarylamino, C 1 -C 4 alkylthio, arylthio, acylthio, heterocyclic-carbonylthio, heterocyclicthio, C 1 - C 4 alkylimidoylthio, arylimidoylthio, amidinothio, di-C 1 -C 4 alkylamidinothio, diarylamidinothio, C 1 -C 4 alkoxy-C 1 -C 4 alkoxythiocarbonylthio, aryloxy-C 1 -C 4 alkoxy thiocarbonylthio, N - C 1 -C 4 alkylaminothiocarbonylthio, N- arylaminothiocarbonylthio, N - C 1 -C 4 - alkyl- N - arylaminothiocarbonylthio, N,N - di - lower alkylaminothiocarbonylthio where the di-C 1 - C 4 -alkylamino groups may form a monocyclic heterocyclic radical with or without an oxygen atom or an additional N atom in the ring so formed; R 5 is OH, O-, alkoxy, aryloxy, heterocyolic-C 1 -C 4 alkoxy, hydroxyamino, alkylamino, C 1 -C 4 alkylthio or heterocyclicthio. The compounds are prepared by (A) acylating 7-aminocephalosporanic acid with a sydnone compound of Formula III in which R 1 , R 2 , R 3 and Z have the above meanings, or a reactive derivative thereof to obtain the corresponding 7-substituted compound of Formula IV in which R 1 , R 2 , R 3 and Z have the above meanings; and, if needed, (B) reacting compound IV with the appropriate nucleophile to obtain the 3-substituted compound of Formula V in which R 1 , R 2 , R 3 and Z have the above meanings, R 4 <SP>1</SP> is the same as R 4 except acetoxy; and then, if needed, (C) treating the 7-substituted compound (IV) or the 3-substituted compound (V) with the appropriate alcohol, thiol, alkyl halide or amine to obtain the corresponding 4-substituted compound of Formula I; and, if needed, (D) forming the salt of compound I. The salts are the alkali metal salts, ammonium, and salts of diphenylenediamine, dicyclohexylamine, N - methyl - N - n - butoxyethylbenzylamine, N,N - di - n - butoxyethylbenzylamine, tri - n - butoxyethylamine, N - methylpiperazine, N - methyl - 4 - chloropiperidine, N- methylmorpholine, guanyl urea, triethylamine and others. The compounds of Formula I are active against both gram-positive and gramnegative organisms.