Synthesis and antibacterial activities of some chloro analogs of 3-amino-3,4-dihydro-1-hydroxycarbostyril

• Published in: Journal of medicinal chemistry 1975-07, Vol.18 (7), p.752-755
• Main Authors: Davis, Alvie L, Chambers, William H, Kelley, Don H, Fell, David A, Haynes, John R, Hulme, Karen L, Gage, Larry D, McCord, Tommy J
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Escherichia coli - drug effects; Hydroxyquinolines - chemical synthesis; Lactobacillus - drug effects; Leuconostoc - drug effects; Microbial Sensitivity Tests; Piperidines - chemical synthesis; Piperidones - chemical synthesis; Piperidones - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00241a022

The effects of a chloro substituent upon the microbiological activities of 3-amino-3,4-dihydro-1-hydroxycarbostyril were determined. The 5-, 6-, and 7-chloro analogs were synthesized by reductive cyclizations of the appropriately chloro-substituted o-nitrophenylalanines, while the 8-chloro analog was obtained from the N-trifluoroacetyl-3-chloro-2-nitrophenylalanine ethyl ester. All of these compounds were observed to inhibit the growth of Escherichia coli 9723, Leuconostoc dextranicum 8086, and Lactobacillus plantarum 8014. The relative inhibitory activities of the chloro analogs were 7-Cl greater than 6-Cl greater than 8-Cl greater than 5-Cl in E. coli and 7-Cl greater than 6-Cl greater than 8-Cl = 5-Cl in L. dextranicum and L. plantarum. In each of the three microorganisms, the 7-Cl analog was a more effective growth inhibitor than the parent unsubstituted compound. The growth inhibitory activities of this class of compounds were demonstrated to be much more effective than those of the four corresponding lactams, the 5-, 6-, 7-, and 8-chloro analogs of 3-amino-3,4-dihydrocarbostyril.