ABSTRACT
Over 50 phenyl thiazolyl urea and carbamate derivatives were synthesized for evaluation as new inhibitors of bacterial cell-wall biosynthesis. Many of them demonstrated good activity against MurA and MurB and gram-positive bacteria including MRSA, VRE and PRSP. 3,4-Difluorophenyl 5-cyanothiazolylurea (3p) with clog P of 2.64 demonstrated antibacterial activity against both gram-positive and gram-negative bacteria.
Subject(s)
Anti-Bacterial Agents/pharmacology , Carbamates/chemistry , Carbamates/pharmacology , Peptidoglycan/biosynthesis , Phenylthiazolylthiourea/analogs & derivatives , Phenylthiazolylthiourea/pharmacology , Cell Wall/drug effects , Cell Wall/enzymology , Enterococcus faecalis/drug effects , Enterococcus faecalis/enzymology , Escherichia coli/drug effects , Escherichia coli/enzymology , Microbial Sensitivity Tests , Staphylococcus/drug effects , Staphylococcus/enzymologyABSTRACT
Novel tricyclic benzazepine derivatives were synthesized as arginine vasopressin (AVP) antagonists. Several tricyclic compounds showed potent antagonistic activity in rat AVP receptors V(1a) and V(2). Derivatives containing pyrrolo-tricyclic amines, 13i-k, 30, and 31 also showed selectivity for the V(2) receptor.
Subject(s)
Arginine Vasopressin/antagonists & inhibitors , Benzazepines/chemical synthesis , Benzazepines/pharmacology , Animals , Dose-Response Relationship, Drug , Indicators and Reagents , Kidney Medulla/drug effects , Kidney Medulla/metabolism , Liver/drug effects , Liver/metabolism , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Urodynamics/drug effectsABSTRACT
A series of benzodiazepine inhibitors of the MMPs and TACE has been developed. These compounds display an interesting selectivity profile and should be useful tools for exploring the biological relevance of such selectivity.
