title: Substituted azaquinazolinones as modulators of GHSr-1a for the treatment of type II diabetes and obesity.
abstract: Substituted azaquinazolinones were identified as antagonists of the GHSr-1A receptor for the treatment of type II diabetes and obesity. Optimisation for potency and LogD lead to the identification of orally bioavailable, potent antagonists with improved selectivity over hERG.
authors.affiliation: Medicinal Chemistry, Prosidion Ltd, Oxford, United Kingdom. hanrahanpatrick@yahoo.co.uk
authors.forename: Patrick
authors.initials: P
authors.lastname: Hanrahan
authors.forename: James
authors.initials: J
authors.lastname: Bell
authors.forename: Gillian
authors.initials: G
authors.lastname: Bottomley
authors.forename: Stuart
authors.initials: S
authors.lastname: Bradley
authors.forename: Phillip
authors.initials: P
authors.lastname: Clarke
authors.forename: Eleanor
authors.initials: E
authors.lastname: Curtis
authors.forename: Susan
authors.initials: S
authors.lastname: Davis
authors.forename: Graham
authors.initials: G
authors.lastname: Dawson
authors.forename: James
authors.initials: J
authors.lastname: Horswill
authors.forename: John
authors.initials: J
authors.lastname: Keily
authors.forename: Gary
authors.initials: G
authors.lastname: Moore
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Rasamison
authors.forename: Jason
authors.initials: J
authors.lastname: Bloxham
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D015195:Drug Design; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D051638:Ether-A-Go-Go Potassium Channels; D007004:Hypoglycemic Agents; D052999:Quinazolinones; D054440:Receptors, Ghrelin