Publication Abstract from PubMed
A series of substituted 3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors, which have potential as antidiabetic agents, is described. Initial members of the series showed good enzyme inhibitory potency but poor physical properties. Optimisation of the 1-substituent led to 2,3-dihydroxypropyl compounds which showed good in vitro potency and improved physical properties, together with good DMPK profiles and acute in vivo efficacy in a rat model. X-ray crystallographic data are presented, showing an unexpected variety of binding orientations at the dimer interface site.
Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors.,Birch AM, Kenny PW, Oikonomakos NG, Otterbein L, Schofield P, Whittamore PR, Whalley DP Bioorg Med Chem Lett. 2007 Jan 15;17(2):394-9. Epub 2006 Oct 19. PMID:17095214[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
