Synthesis and biological activities of novel indole derivatives as potent and selective PPARgamma modulators

Yann Lamotte; Paul Martres; Nicolas Faucher; Alain Laroze; Didier Grillot; Nicolas Ancellin; Yannick Saintillan; Véronique Beneton; Robert T Gampe Jr

doi:10.1016/j.bmcl.2009.12.107

Synthesis and biological activities of novel indole derivatives as potent and selective PPARgamma modulators

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1399-404. doi: 10.1016/j.bmcl.2009.12.107. Epub 2010 Jan 4.

Authors

Yann Lamotte¹, Paul Martres, Nicolas Faucher, Alain Laroze, Didier Grillot, Nicolas Ancellin, Yannick Saintillan, Véronique Beneton, Robert T Gampe Jr

Affiliation

¹ Department of Medicinal Chemistry, Laboratoire GlaxoSmithKline, Centre de Recherches, 25-27 Avenue du Québec, 91951 Les Ulis, France. yann.lamotte@gsk.com

PMID: 20079636
DOI: 10.1016/j.bmcl.2009.12.107

Abstract

Starting from the structure of Telmisartan, a new series of potent and selective PPARgamma modulators was identified. The synthesis, in vitro and in vivo evaluation of the most potent compounds are reported and the X-ray structure of compound 7b bound to the PPARgamma ligand binding domain is described.

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / chemistry
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Animals
Benzimidazoles / chemistry
Benzimidazoles / pharmacology
Benzoates / chemistry
Benzoates / pharmacology
Crystallography, X-Ray
Drug Design*
Humans
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
PPAR gamma / drug effects*
Rats
Structure-Activity Relationship
Telmisartan

Substances

Angiotensin-Converting Enzyme Inhibitors
Benzimidazoles
Benzoates
Indoles
PPAR gamma
Telmisartan