1. Substituted azaquinazolinones as modulators of GHSr-1a for the treatment of type II diabetes and obesity
- Author
-
Susan Helen Davis, Gillian A. Bottomley, Chrystelle Marie Rasamison, Phillip Clarke, Eleanor Curtis, James Charles Bell, John Keily, Patrick Eric Hanrahan, Gary Moore, Stuart Bradley, Graham Dawson, Jason Bloxham, and James G. Horswill
- Subjects
Male ,medicine.medical_specialty ,Clinical Biochemistry ,hERG ,Pharmaceutical Science ,Administration, Oral ,Biological Availability ,Pharmacology ,Biochemistry ,Type ii diabetes ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,Internal medicine ,Diabetes mellitus ,Drug Discovery ,medicine ,Structure–activity relationship ,Potency ,Animals ,Humans ,Hypoglycemic Agents ,Obesity ,Receptor ,Receptors, Ghrelin ,Molecular Biology ,Quinazolinones ,Aza Compounds ,biology ,Chemistry ,Organic Chemistry ,medicine.disease ,Ether-A-Go-Go Potassium Channels ,Rats ,Kinetics ,Endocrinology ,Diabetes Mellitus, Type 2 ,Drug Design ,biology.protein ,Molecular Medicine ,Ghrelin ,Hydrophobic and Hydrophilic Interactions - 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.
- Published
- 2011