170147-88-3Relevant articles and documents
Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: Pharmacophore-based virtual screening, synthesis, and pharmacology
Chaudhaery, Shailendra S.,Roy, Kuldeep K.,Shakya, Neeraj,Saxena, Gunjan,Sammi, Shreesh Raj,Nazir, Aamir,Nath, Chandishwar,Saxena, Anil K.
, p. 6490 - 6505 (2010)
A systematic virtual screening (VS) experiment, consisting of the development of 3D-pharmacophore, screening of virtual library, synthesis, and pharmacology, is reported. The predictive pharmacophore model (correlation = 0.955) with one H-bond donor and three hydrophobic features was developed using HypoGen on a training set of 24 carbamates as AChE inhibitors. The model was validated on a test set of 40 carbamates (correlation = 0.844). The pharmacophore-based VS of virtual library led to the identification of novel carbamates as potent AChE inhibitors. The synthesis and pharmacological evaluation of nine carbamates against three diverse assay systems, namely (i) in vitro Ellman method, (ii) in vivo passive avoidance test, and (iii) aldicarb-sensitivity assay, led to the discovery of orally active novel AChE inhibitors which improved scopolamine-induce cognition impairment in Swiss male mice. Finally, two novel lead compounds 85 and 86 are selected as candidate molecules for further optimization.
Substituted 1,2,3,4-tetrahydroquinolin-6-yloxypropanes as β3-adrenergic receptor agonists: Design, synthesis, biological evaluation and pharmacophore modeling
Shakya, Neeraj,Roy, Kuldeep K.,Saxena, Anil K.
experimental part, p. 830 - 847 (2009/07/25)
In search of potent β3-adrenergic receptor agonists, a series of novel substituted 1,2,3,4-tetrahydroquinolin-6-yloxypropanes has been synthesized and evaluated for their β3-adrenergic receptor agonistic activity (ranging from -17.73% to 90.64% inhibition at 10 μM) using well established Human SK-N-MC neuroblastoma cells model. Four molecules viz. 11, 15, 22 and 23 showed β3-AR agonistic IC50 value of 0.55, 0.59, 1.18 and 1.76 μM, respectively. These four candidates have been identified as possible leads for further development of β3-adrenergic receptor agonists for obesity and Type-II diabetes pharmacotherapy. The free OH and NH functions are found to be essential for β3-adrenergic receptor agonistic activity. Among the synthesized β3-adrenergic receptor agonists having 1,2,3,4-tetrahydroquinoline scaffold, the N-benzyl group is found to be superior over N-arylsulfonyl group. A putative pharmacophore model has been modeled considering the above four active molecules which distinguishes well between the active and inactive molecules.
