PENICILLIN DERIVATIVES

摘要

1283099 Penicillins AMERICAN HOME PRODUCTS CORP 6 Nov 1969 [20 Nov 1968 (2)] 54389/69 Heading C2A Novel 6 - (1 - aminocyclopentene - 1 - carboxamido) penicillanic acids of formula (A) and their non-toxic salts, wherein Z is -NHR1 or a protected amino group, R1 is H, C 1 -C 7 alkyl or phenyl (C 1 -C 7 ) alkyl, and the dotted line represents a second bond in one of the two designated positions, are prepared by acylating 6-amino-penicillanic acid or its salt or silyl or silenyl derivative with an acid of formula or a functional acylating derivative thereof, and optionally removing the amino - protecting group. The compounds (A) above wherein Z is NHR1 may be condensed with an aldehyde or ketone of formula R2R3CO to give novel 6-(4-oxo-1,3- diazaspiro[4,4]nonen - 3 - yl) penicillanic acids of formula (B) or their non-toxic salts, wherein R2 and R3 are each H, C 1 -C 7 alkyl or phenyl, or when taken together with the carbon atom to which they are attached form a C 3 -C 7 cycloalkyl ring, and R1 and the dotted line are as defined above. The preferred acylating agent is the N-carboxy-anhydride of the acid, which is a 3 - oxa - 1 - azaspiro[4,4]nonene - 2,4 - dione of formula wherein R1 is as above. Pharmaceutical compositions having antibacterial activity against gram-positive and gram-negative bacteria comprise a penicillin of formula (A), wherein Z is -NHR1 as defined above or of formula (B), or a non-toxic salt thereof together with a pharmaceutically acceptable carrier.