Acylamido-methyl penicillin and cephalosporin esters - for oral administration and subsequent in-tissue enzymic hydrolysis to parent antibiotic

摘要

Penicillins and cephalosporins of the formula (I) and their acids addn. salts are novel:- (where A-B = R and R1 are each H or (1-4C) alkyl; R2 (up to 10C) straight or branched alkyl substd. by 1 to 3 halogen or R1 and R2 together = -(CH2)n-; n = 2 to 5; R3 = H or methoxy; R4 = benzyl, thienyl-(2)-methyl, furyl-(2)- methyl, phenoxymethyl, 1-phenoxyethyl, 1-phenoxypropyl, alpha-phenoxybenzyl, 2,6-dimethoxyphenyl, (alpha-carboxy ester) benzyl, 1-(opt. substd. amino)benzyl or (nuclear hydroxy, amino or fluoro mono-substd. benzyl), 3-phenyl-5-methyl-isoxazolyl-(4) (or derivs thereof mono- or di-hydroxy, amino, chloro, fluoro substd. on the phenyl group), cyclohexa-1,4-dienyl-aminomethyl, 1-aminocyclohexyl-(1), 2-ethoxynaphthyl-(1), 2-carboxyquinoxalinyl-(3) or 1,2,3,4-tetrazolyl-1-methyl; R5 = H or acetoxy). (I) are antibacterial agents which are tasteless and may be administered orally whereas the parent antibiotic may have to be given parenterally. (I) are hydrolysed by enzymes in the tissues to give the parent antibiotic in situ. M.I.C. against Staphylococcus aureus for dicloxacillin dichloracetamidomethyl ester was 0.015 ug/ml.