Non-basic ligands for aminergic GPCRs: The discovery and development diaryl sulfones as selective, orally bioavailable 5-HT 2A receptor antagonists for the …

…, M Ivarsson, M Dominguez, D O'Connor…

Index: Ladduwahetty, Tammy; Gilligan, Myra; Humphries, Alexander; Merchant, Kevin J.; Fish, Rebecca; McAlister, George; Ivarsson, Magnus; Dominguez, Maria; O'Connor, Desmond; MacLeod, Angus M. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 12 p. 3708 - 3712

Full Text: HTML

Citation Number: 5

Abstract

Scaffold hopping from a non-basic series of 5-HT2A receptor antagonists developed in- house that possessed reduced activity in vivo enabled the discovery of a novel series of diaryl sulfones that gave excellent occupancy on oral dosing. Not only does this work further demonstrate that oral bioavailability of a given series can be enhanced by improving physicochemical parameters such as logP, but it corroborates the growing evidence that a ...