GB1364453A - Penicillanic and cepholosporanic acid derivatives - Google Patents

Abstract

1364453 Penicillins and cephalosporins GIST-BROCADES NV 5 Nov 1971 [6 Nov 1970] 53040/70 Heading C2A The invention comprises penicillanic and cephalosporanic acid derivatives of the general Formula I in which Q represents the Group II or the Group III (wherein X represents a hydrogen atom, a hydroxy group, or a lower alkanoyloxy group, or the grouping -CH 2 X and the carboxy group in Formula III are linked together to form a lactone or lactam group, R represents a lower alkyl or an adamantyl group, or an aryl group optionally carrying one or more substituents selected from chlorine and fluorine atoms, and nitro, amino and lower alkyl groups, R<SP>1</SP> represents a hydrogen or a chlorine atom, a lower alkyl group, a carbamoyl, cyano or amino group, or a carboxy group optionally esterified with a lower alkyl group or transformed into an alkali metal, alkaline earth metal or amine salt, and R<SP>2</SP> represents a hydrogen or halogen atom, a cyano or amino group, a phenyl (lower) alkoxycarbonylamino group optionally substituted on the phenyl ring, or R<SP>2</SP> represents a lower alkyl group, a carboxy group esterified with a lower alkyl or benzyl group, or a carbamoyl group optionally carrying on the nitrogen atom a lower alkyl or phenyl substituent) and alkali metal, alkaline earth metal and amine salts, esters and amides of the compounds of Formula I. The compounds of Formula I may be prepared by reacting a salt, ester or amide of a compound of Formula IV or of Formula V wherein the substituent X, if a hydroxy group is preferably protected with a 2,4-dinitrophenyl ester, p-nitrophenyl ester or N-hydroxysuccinimide ester group, with an acid of general Formula VI or an acylating derivative thereof. A further method for the preparation of compounds of Formula I comprises reacting an acid of general Formula VI in which the reactive groups R, R<SP>1</SP> and R<SP>2</SP> are suitably protected, with a 6-isocyanatopenicillanic acid or 7 - isocyanatocephalosporanic acid of formula O = C = N-Q in which carboxy and hydroxy groups if present are protected, e.g. by di- or tri-alkylsilyl group. A still further method of preparation of compounds of general Formula I comprises reacting the above isocyanato compounds with organometal compounds of formula A-Me<SP>I</SP>, A-Me<SP>II</SP>-Hal or A-Me<SP>11</SP>-A in which Me represents a metal atom whose valency is indicated by the numeral I or II. Therapeutic compositions comprise an effective amount of a penicillanic or cephalosporanic acid compound of Formula I in conjunction with a pharmaceutically acceptable carrier or excipient.