SEMISYNTHETIC β-LACTAM ANTIBIOTICS

III. EFFECT ON ANTIBACTERIAL ACTIVITY AND COMTSUSCEPTIBILITY OF CHLORINE-INTRODUCTION INTO THE CATECHOL NUCLEUS OF 6-[(R)-2-[3-(3, 4-DIHYDROXYBENZOYL)-3-(3-HYDROXYPROPYL)4-UREIDO]-2-PHENYLACETAMIDO]PENICILLANIC ACID

Abstract

The resistance of 6-[(R)-2-[3-(3, 4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido]-2-phenylacetamido]penicillanic acid (1a) to metabolism by catechol-O-methyl-transferase (COMT) was increased by introduction of the chlorine atom into the catechol moiety. Penicillins (1b-1d) having one or two chlorine atoms at the positions adjacent to the hydroxyl group were found to have greater stability to COMT. This resulted in greater efficiency in vivo in experimental Pseudomonas aeruginosa and Escherichia coll infections. In vitro activities were essentially unchanged.