Identification and optimisation of novel sulfonamide, selective vasopressin V sub(1B receptor antagonists)

The synthesis and preliminary structure-activity relationships (SAR) of a novel class of vasopressin V sub(1B receptor antagonists are described. Hit compound 5, identified via high throughput screening of the corporate collection, showed good activity in a V) sub(1)B binding assay (K sub(i 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 V) sub(1)B antagonist 9f (K sub(i 190 nM), with improved druglike characteristics. AB:)