Synthesis and biological activities of novel indole derivatives as potent and selective PPARgamma modulators.
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.
Lamotte
Yann
Y
Department of Medicinal Chemistry, Laboratoire GlaxoSmithKline, Centre de Recherches, 25-27 Avenue du Québec, 91951 Les Ulis, France. yann.lamotte@gsk.com
Martres
Paul
P
Faucher
Nicolas
N
Laroze
Alain
A
Grillot
Didier
D
Ancellin
Nicolas
N
Saintillan
Yannick
Y
Beneton
Véronique
V
Gampe
Robert T
RT
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D047495:PPAR gamma / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship; D000077333:Telmisartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D007211:Indoles; D047495:PPAR gamma; D000077333:Telmisartan