Hydroxy-pyridazinyl-ureido-beta-lactam antibiotics - with broad spectrum antibacterial activity prepd. e.g. by reacting alpha-amino-penicillin with 3-hydroxy-4-pyridazinyl isocyanate

摘要

Ureido-substd. beta-lactam antibiotics of formula (I) and, when E is H, their pharmacologically tolerable salts with organic and inorganic bases, are new. In (I), A is phenyl, p-hydroxyphenyl, 2- or 3-thienyl, 2- or 3-furyl, cyclohexyl, cyclohexen-1-yl, cyclohexa-1,4-dien-1-yl, or phenyl substd. in the 3,4-position by Cl, OH and/or OMe; R is H, or 1-4C aliphatic hydrocarbon residue; phenyl, 3-6C cycloalkyl, OH, 1-4C alkoxy, SH, 1-4C alkylmercapto, amino, mono- or di(1-6C alkyl)amino, anilino, morpholino, 1-4C acylamino, Cl, Br or NO2; X is a group of formula (Ia) or (Ib); D is H, acetoxy, carbamoyloxy or -S-Het; Het is 3-methyl-1,2,4-thiadiazol-5-yl, 2-methyl-1,3,4-oxadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 2-methyl-1,3,4-thiadiazol-5-yl, tetrazol-5-yl, 1-methyl-tetrazol-5-yl or 1,2,3-triazol-4-yl; and E is H or a protecting group which is easily cleaved off in vitro or in vivo. (I) are antibacterials with a broad spectrum of activity against gram-positive and gram-negative organisms, and are well tolerated in man. They can be used in the treatment of local and systemic infections. In addition, (I) can be used as preservatives for organic and inorganic materials and foodstuffs. Many of the cpds. (I) show activity against E.coli and Ps. aeruginosa, in some cases at concentrations of less than 10 ug/ml.