Abstract
Serotonin type 3 (5-HT3) receptor partial agonists have been targeted as potential new drugs for the symptomatic relief of irritable bowel syndrome (IBS). Multiple diazepinone-based compounds have been discovered, which exhibit nanomolar binding affinity for the h5-HT3A receptor and display a range of intrinsic activities (IA=7-87% of 5-HT Emax) in HEK cells heterologously expressing the h5-HT3A receptor. Favorable physicochemical properties and in vitro ADME profile coupled with oral activity in the murine von Bezold-Jarisch reflex model demonstrates the series has promise for producing low to moderate IA partial agonists suitable for an IBS indication.
Original language | English |
---|---|
Pages (from-to) | 2578-81 |
Number of pages | 4 |
Journal | Bioorganic & Medicinal Chemistry Letters |
Volume | 24 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Jun 2014 |