Xanthine oxidase inhibitors fall into two classes, those which co not (e.g. febuxostat). Recently we discovered a novel pyrimidine enzymatic assays. Molecular docking studies showed binding pattern similar to that of febuxostat. Shifting a nitrogen …
A series of novel 2-amino-4-pyrazolecyclopentylpyrimidines have been prepared and evaluated as IGF-1R tyrosin kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 2- amino ring, 4-pyrazolo moieties …
Metabolic syndrome is a widely prevalent multifactorial disorder associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. High plasma levels of insulin and glucose due to insulin resistance are a major component of …
Thiazolidinediones (TZDs) are an important class of compound used for the treatment of type 2 diabetes, targeting the peroxisome proliferator-activated receptor γ (PPARγ). Drug-induced hepatotoxicity, edema, and weight gain are the main concerns …
We report our attempts at improving the oral efficacy of low-nanomolar inhibitors of xanthine oxidase from isocytosine series through chemical modifications. Our lead compound had earlier shown good in vivo efficacy when administered …
The thiazolidinediones (TZDs) are a class of oral antidiabetic drugs that improve insulin sensitivity in patients with type 2 diabetes. Although the mechanism by which the TZDs lower insulin resistance is unclear, they are known to target the …
Structure-activity relationship studies were carried out for lead generation following structure-guided design approach from an isocytosine scaffold identified earlier for xanthine oxidase inhibition. A 470-fold improvement in in vitro IC(50) was …
In recent years, xanthine oxidase has emerged as an important target not only for gout but also for cardiovascular and metabolic disorders involving hyperuricemia. Contrary to popular belief, recent clinical trials with uricosurics have demonstrated …
A promising therapeutic approach to diminish pathological inflammation is to inhibit the synthesis and/or biological activity of macrophage migration inhibitory factor (MIF). Prior studies have shown that intraperitoneal administration of …
Docking, virtual screening and structure-based drug design are routinely used in modern drug discovery programs. Although current docking methods deal with flexible ligands, managing receptor flexibility has proved to be challenging. In this brief …