Identification and optimization of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl)acetamide vasopressin V3 (V1b) receptor antagonists

Letourneau, J. J. et al. (2010) Identification and optimization of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl)acetamide vasopressin V3 (V1b) receptor antagonists. Bioorganic and Medicinal Chemistry Letters, 20(18), pp. 5394-5397. (doi: 10.1016/j.bmcl.2010.07.118)

Abstract

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 μM), but less than desirable physicochemical properties. Optimization of compound 1 yielded potent analogs 19 (IC50 = 0.31 μM) and 24 (IC50 = 0.12 μM) with improved drug-like characteristics.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Thomson, Dr Fiona
• Authors: Letourneau, J. J., Riviello, C. M., Li, H., Cole, A. G., Ho, K.-K., Zanetakos, H. A., Desai, H., Zhao, J., Auld, D. S., Napier, S. E., Thomson, F. J., Goan, K. A., Morphy, J. R., Ohlmeyer, M. H.J., and Webb, M. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Bioorganic and Medicinal Chemistry Letters
• Publisher: Elsevier
• ISSN: 0960-894X
• Published Online: 03 August 2010