2. Academic Validation
  3. Discovery of benzothiazole derivatives as efficacious and enterocyte-specific MTP inhibitors

Discovery of benzothiazole derivatives as efficacious and enterocyte-specific MTP inhibitors

  • Bioorg Med Chem Lett. 2009 Mar 1;19(5):1416-20. doi: 10.1016/j.bmcl.2009.01.044.
Chi B Vu 1,  Jill C Milne,  David P Carney,  Jeffrey Song,  Wendy Choy,  Philip D Lambert,  David J Gagne,  Michael Hirsch,  Angela Cote,  Meghan Davis,  Elden Lainez,  Nekeya Meade,  Karl Normington,  Michael R Jirousek,  Robert B Perni
Affiliations

Affiliation

  • 1 Sirtris Pharmaceuticals, Departments of Medicinal Chemistry, Lead Discovery and Pharmacology, 200 Technology Square, Cambridge, MA 02139, USA.
PMID: 19181526 DOI: 10.1016/j.bmcl.2009.01.044
Abstract

A series of triamide derivatives bearing a benzothiazole core is shown to be potent microsomal triglyceride transfer protein (MTP) inhibitors. In order to minimize liver toxicity, these compounds have been optimized to have activity only in the enterocytes and have limited systemic bioavailability. Upon oral administration, selected analogs within this series have been further demonstrated to reduce food intake along with body weight and thereby improve glucose homeostasis and Insulin sensitivity in a 28-day mice diet-induced obesity (DIO) model.

Figures