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ID: ALA2034922
Journal: Bioorg Med Chem Lett
Title: Identification, optimisation and in vivo evaluation of oxadiazole DGAT-1 inhibitors for the treatment of obesity and diabetes.
Authors: McCoull W, Addie MS, Birch AM, Birtles S, Buckett LK, Butlin RJ, Bowker SS, Boyd S, Chapman S, Davies RD, Donald CS, Green CP, Jenner C, Kemmitt PD, Leach AG, Moody GC, Gutierrez PM, Newcombe NJ, Nowak T, Packer MJ, Plowright AT, Revill J, Schofield P, Sheldon C, Stokes S, Turnbull AV, Wang SJ, Whalley DP, Wood JM.
Abstract: A novel series of DGAT-1 inhibitors was discovered from an oxadiazole amide high throughput screening (HTS) hit. Optimisation of potency and ligand lipophilicity efficiency (LLE) resulted in a carboxylic acid containing clinical candidate 53 (AZD3988), which demonstrated excellent DGAT-1 potency (0.6 nM), good pharmacokinetics and pre-clinical in vivo efficacy that could be rationalised through a PK/PD relationship.
CiteXplore: 22608962