438003-11-3Relevant academic research and scientific papers
Discovery of novel indazole derivatives as dual angiotensin II antagonists and partial PPARγ agonists
Lamotte, Yann,Faucher, Nicolas,Sancon, Julien,Pineau, Olivier,Sautet, Stephane,Fouchet, Marie-Helene,Beneton, Veronique,Tousaint, Jean-Jacques,Saintillan, Yannick,Ancellin, Nicolas,Nicodeme, Edwige,Grillot, Didier,Martres, Paul
, p. 1098 - 1103 (2014/03/21)
Identification of indazole derivatives acting as dual angiotensin II type 1 (AT1) receptor antagonists and partial peroxisome proliferator-activated receptor-γ (PPARγ) agonists is described. Starting from Telmisartan, we previously described that indole derivatives were very potent partial PPARγ agonists with loss of AT1 receptor antagonist activity. Design, synthesis and evaluation of new central scaffolds led us to the discovery of pyrrazolopyridine then indazole derivatives provided novel series possessing the desired dual activity. Among the new compounds, 38 was identified as a potent AT1 receptor antagonist (IC50 = 0.006 μM) and partial PPARγ agonist (EC50 = 0.25 μM, 40% max) with good oral bioavailability in rat. The dual pharmacology of compound 38 was demonstrated in two preclinical models of hypertension (SHR) and insulin resistance (Zucker fa/fa rat).
Synthesis and biological activities of novel indole derivatives as potent and selective PPARγ modulators
Lamotte, Yann,Martres, Paul,Faucher, Nicolas,Laroze, Alain,Grillot, Didier,Ancellin, Nicolas,Saintillan, Yannick,Beneton, Véronique,Gampe Jr., Robert T.
scheme or table, p. 1399 - 1404 (2010/07/06)
Starting from the structure of Telmisartan, a new series of potent and selective PPARγ 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 PPARγ ligand binding domain is described.
