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ABSTRACT: Optimization of the novel alpha-2-delta-1 ligand 4 provided compounds 37 and 38 which have improved DMPK profiles, good in vivo analgesic activity and in vitro selectivity over alpha-2-delta-2. An in-house P-gp prediction programme and the MetaSite software package were used to help solve the specific problems of high P-gp efflux and high in vivo clearance.
Bioorganic & medicinal chemistry letters 08/2010; 20(15):4683-8. DOI:10.1016/j.bmcl.2010.05.026 · 2.42 Impact Factor