1402151-29-4Relevant academic research and scientific papers
Lead optimization studies towards the discovery of novel carbamates as potent AChE inhibitors for the potential treatment of Alzheimer's disease
Roy, Kuldeep K.,Tota, Santoshkumar,Tripathi, Tusha,Chander, Subhash,Nath, Chandishwar,Saxena, Anil K.
, p. 6313 - 6320 (2012/11/13)
The optimization of our previous lead compound 1 (AChE IC50 = 3.31 μM) through synthesis and pharmacology of a series of novel carbamates is reported. The synthesized compounds were evaluated against mouse brain AChE enzyme using the colorimetric method described by Ellman et al. The three compounds 6a (IC50 = 2.57 μM), 6b (IC50 = 0.70 μM) and 6i (IC50 = 2.56 μM) exhibited potent in vitro AChE inhibitory activities comparable to the drug rivastigmine (IC50 = 1.11 μM). Among them, the compound 6b has been selected as possible optimized lead for further neuropharmacological studies. In addition, the AChE-carbamate Michaelis complexes of these potent compounds including rivastigmine and ganstigmine have been modeled using covalent docking protocol of GOLD and important direct/indirect interactions contributing to stabilization of the AChE-carbamate Michaelis complexes have been investigated.
