1207604-15-6Relevant articles and documents
Design, synthesis, and docking studies of novel benzimidazoles for the treatment of metabolic syndrome
Mizuno, Cassia S.,Chittiboyina, Amar G.,Shah, Falgun H.,Patny, Akshay,Kurtz, Theodore W.,Pershadsingh, Harrihar A.,Speth, Robert C.,Karamyan, Vardan T.,Carvalho, Paulo B.,Avery, Mitchell A.
supporting information; experimental part, p. 1076 - 1085 (2010/08/06)
In addition to lowering blood pressure, telmisartan, an angiotensin (AT1) receptor blocker, has recently been shown to exert pleiotropic effects as a partial agonist of nuclear peroxisome proliferator-activated receptor γ (PPARγ). On the basis of these findings and docking pose similarity between telmisartan and rosiglitazone in PPARγ active site, two classes of benzimidazole derivatives were designed and synthesized as dual PPARγ agonist/angiotensin II antagonists for the possible treatment of metabolic syndrome. Compound 4, a bisbenzimidazole derivative showed the best affinity for the AT1 receptor with a Ki=13.4 nM, but it was devoid of PPARγ activity. On the other hand 9, a monobenzimidazole derivative, showed the highest activity in PPARγ transactivation assay (69% activation) with no affinity for the AT1 receptor. Docking studies lead to the designing of a molecule with dual activity, 10, with moderate PPARγ activity (29%) and affinity for the AT1 receptor (Ki=2.5 μM).
