3-Imino-acetamido-azetidinone-1-sulphonic acid derivs. - with broad spectrum antibacterial activity

摘要

3-Acylaminoazetidinone derivs. of formula (I) in racemic and 35 enantiomeric forms and their salts (N-ring is an aromatic, 5 or 6 membered heterocycle contg. 1 or 2 N and opt. an O, S or Se atom. R1 is alkyl opt. substd. (a) by alkynyl, halo, azido, amino (itself opt. substd. by 1,2 or 3 alkyl), alkanoyloxyamino, benzenesulphonamido , thiocyanato, hydroxy, alkanoyloxy, carbamoyloxy, carbamoyl , hydroxy- or alkoxy-aminocarbonyl, sulpho, sulphothio, phosphonato (opt. mono- or di-alkyl substd.), sulphamoyl, alkylthio, alkylsulphinyl or alkylsulphonyl; or (b) by a 5-7 membered, aromatics (un)satd. N-contg. heterocyclyl (carbonyl) R2 is H or lower organic gp. The = NOR1 gp. exists at least partly in the syn-form). Also new are intermediates (IIa) and (IId) and the cpd. 2-(2-amino-4-thiazolyl)- 2-((Z)-(IH-tetrazol-5-ylmethoxy) imino) acetic acid. (R10 is alkyl substd. as R1 but not by halo, azido, amino, monoalkyl, amino, trialkylammonio, sulpho, sulphothio, phosphoro or hydroxyaminocarbonyl, and not substd. in a heterocyclic substit. by monoalkylamino or sulphoalkyl; but R10 may have as additional substits. alkanesulphonamido or cyano. R is opt. substd. amino. R12 is alkyl substd. by thiocyanato, alkanoyloxyimino, alkanesulphonamido, benzenesulphonamido alkanoyloxy, carbamoyloxy, hydroxy- or alkoxy-aminocarbonyl, sulpho, sulphothio, sulphamoyl, alkylthio, alkylsulphinyl, alkylsulphonyl or CONR7R8. R7 and R8 are each alkyl or together are 4-6C alkylene opt. substd. by alkyl, carbamoyl, sulphoalkyl or mono- or di-alkylamino. . (I) are broad-spectrum antibacterial, esp. useful against gram negative species such as E.coli, Proteus and Serratia species and Pseudomona aeruginosa. Typical daily doses are 10-600 mg per kg.