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Bioorg Med Chem Lett. 2012 Jun 15;22(12):3873-8. doi: 10.1016/j.bmcl.2012.04.117. Epub 2012 May 2.

Identification, optimisation and in vivo evaluation of oxadiazole DGAT-1 inhibitors for the treatment of obesity and diabetes.

Author information

1
Cardiovascular & Gastrointestinal Innovative Medicines Unit, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. william.mccoull@astrazeneca.com

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.

PMID:
22608962
DOI:
10.1016/j.bmcl.2012.04.117
[Indexed for MEDLINE]

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