title: Semisynthetic beta-lactam antibiotics. III. Effect on antibacterial activity and comt-susceptibility of chlorine-introduction into the catechol nucleus of 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-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 coli infections. In vitro activities were essentially unchanged.
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D065098:Catechol O-Methyltransferase Inhibitors; D004927:Escherichia coli Infections / Q000188:drug therapy; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy; D013329:Structure-Activity Relationship; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D065098:Catechol O-Methyltransferase Inhibitors; D007202:Indicators and Reagents; D010406:Penicillins; D047090:beta-Lactams; C052009:6-(2-(3-(5-chloro-3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido)-2-phenylacetamido)penicillanic acid; C052008:6-(2-(3-(2-chloro-3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido)-2-phenylacetamido)penicillanic acid; C052007:6-(2-(3-(2,5-dichloro-3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido)-2-phenylacetamido)penicillanic acid