Identification and optimisation of novel sulfonamide, selective vasopressin V1B receptor antagonists

Baker, J. et al. (2011) Identification and optimisation of novel sulfonamide, selective vasopressin V1B receptor antagonists. Bioorganic and Medicinal Chemistry Letters, 21(12), pp. 3603-3607. (doi: 10.1016/j.bmcl.2011.04.104)

Abstract

The synthesis and preliminary structure–activity relationships (SAR) of a novel class of vasopressin V1B receptor antagonists are described. Hit compound 5, identified via high throughput screening of the corporate collection, showed good activity in a V1B binding assay (Ki 63 nM) but did not possess the lead-like physicochemical properties typically required in a hit compound. A ‘deletion approach’ on the HTS hit 5 was performed, with the focus on improvement of physicochemical properties, yielding the selective V1B antagonist 9f (Ki 190 nM), with improved druglike characteristics.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Thomson, Dr Fiona
• Authors: Baker, J., Bingham, M., Blackburn-Munro, R., Cai, J., Craighead, M., Gilfillan, R., Goan, K., Jaap, D., Milne, R., Richard Morphy, J., Napier, S., Presland, J., Spinks, G., and Thomson, F.
• 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: 01 May 2011