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

Abstract

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.

Ligand-Enabled β-C–H Arylation of α-Amino Acids Using a Simple and Practical Auxiliary

“…First reported by Davis and co-workers over thirty years ago, they were shown to exhibit antibacterial activity. 32 More recently, similar scaffolds have been identified as potent inhibitors of KAT II, an enzyme currently being investigated as a therapeutic target for cognitive impairment associated with schizophrenia, among other disorders. 11 Using the above protocols, arylation followed by a known radical cyclization, medicinally important analogues of N -methoxy-3-amino-3,4-dihydroquinolines 14 ′ and 20–22 were prepared in a straightforward manner (Table 12).…”

A General Strategy for the Synthesis of Cyclic N-Aryl Hydroxamic Acids via Partial Nitro Group Reduction

“…The synthesis of N -hydroxy-3-amino-3,4-dihydroquinolinones as antibacterial agents was first reported by Davis and co-workers over thirty years ago ( 1 , Figure ) . More recently, these scaffolds have been identified as potent inhibitors of kynurenine aminotransferase II (KAT II), an enzyme currently being investigated as a therapeutic target for cognitive impairment associated with schizophrenia, among other disorders. , As part of our program to identify optimal KAT II inhibitors, we have extensively explored synthetic approaches to differentially substituted 3-amino-1-hydroxy-3,4-dihydroquinolinones.…”

In vitro antimicrobial activity of some cyclic hydroxamic acids and related lactams

“…1, where X = H (7). Subsequent structure-activity studies show that certain structural modifications of these compounds have pronounced effects on their antibacterial activities (6,(8)(9)(10). Among the various analogs of ADHC and ADC that have been prepared and tested, the 6-and 7-chloro (X = Cl in Fig.…”

“…Among the various analogs of ADHC and ADC that have been prepared and tested, the 6-and 7-chloro (X = Cl in Fig. 1) analogs have been found to be the most effective inhibitors of bacterial growth (6).…”