- Identification and optimization of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl)acetamide vasopressin V3 (V1b) receptor antagonists.
Identification and optimization of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl)acetamide vasopressin V3 (V1b) receptor antagonists.
Bioorganic & medicinal chemistry letters (2010-08-20)
Jeffrey J Letourneau, Christopher M Riviello, Hong Li, Andrew G Cole, Koc-Kan Ho, Heather A Zanetakos, Hema Desai, Jiuqiao Zhao, Douglas S Auld, Susan E Napier, Fiona J Thomson, Katharine A Goan, J Richard Morphy, Michael H J Ohlmeyer, Maria L Webb
PMID20719508
摘要
The discovery, synthesis, and preliminary structure-activity relationship (SAR) of a novel class of vasopressin V3 (V1b) receptor antagonists is described. Compound 1, identified by high throughput screening of a diverse, three million-member compound collection, prepared using ECLiPS technology, had good activity in a V3 binding assay (IC50=0.20 microM), but less than desirable physicochemical properties. Optimization of compound 1 yielded potent analogs 19 (IC50=0.31 microM) and 24 (IC50=0.12 microM) with improved drug-like characteristics.