Benzimidazolones: A New Class of Selective Peroxisome Proliferator-Activated Receptor γ (PPARγ) Modulators was written by Wang, Chualin;McCann, Margaret E.;Doebber, Thomas W.;Wu, Margaret;Chang, Ching H.;McNamara, Lesley;McKeever, Brian;Mosley, Ralph T.;Berger, Joel P.;Meinke, Peter T.. And the article was included in Journal of Medicinal Chemistry in 2011.Formula: C8H6ClNO The following contents are mentioned in the article:
A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPARγ modulators (SPPARγMs) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPARγ full agonist drugs. Structure-activity relationships of these potent and highly selective SPPARγMs were studied with a focus on their unique profiles as partial agonists or modulators. A variety of methods, such as X-ray crystallog. anal., PPARγ transactivation coactivator profiling, gene expression profiling, and mutagenesis studies, were employed to reveal the differential interactions of these new analogs with PPARγ receptor in comparison to full agonists. In rodent models of T2DM, benzimidazolone analogs such as (5R)-5-(3-{[3-(5-methoxybenzisoxazol-3-yl)benzimidazol-1-yl]methyl}phenyl)-5-methyloxazolidinedione I demonstrated efficacy equivalent to that of rosiglitazone. Side effects, such as fluid retention and heart weight gain associated with PPARγ full agonists, were diminished with I in comparison to rosiglitazone based on studies in two independent animal models. This study involved multiple reactions and reactants, such as 3-Chloro-6-methylbenzo[d]isoxazole (cas: 16302-64-0Formula: C8H6ClNO).
3-Chloro-6-methylbenzo[d]isoxazole (cas: 16302-64-0) belongs to benzisoxazole derivatives. The benzisoxazole analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on benzisoxazole-containing compounds. The 1,2-benzisoxazole ring containing drugs zonisamide and risperidone have been used as anticonvulsants.Formula: C8H6ClNO
Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics