Document Report Card
Basic Information
ID: ALA3091421
Journal: Bioorg Med Chem Lett
Title: Discovery of benzo[d]imidazo[5,1-b]thiazole as a new class of phosphodiesterase 10A inhibitors.
Authors: Banerjee A, Narayana L, Raje FA, Pisal DV, Kadam PA, Gullapalli S, Kumar H, More SV, Bajpai M, Sangana RR, Jadhav S, Gudi GS, Khairatkar-Joshi N, Merugu RR, Voleti SR, Gharat LA.
Abstract: The design, synthesis and structure activity relationship studies of a series of compounds from benzo[d]imidazo[5,1-b]thiazole scaffold as phosphodiesterase 10A (PDE10A) inhibitors are discussed. Several potent analogs with heteroaromatic substitutions (9a-d) were identified. The anticipated binding mode of these analogs was confirmed by performing the in silico docking experiments. Later, the heteroaromatics were substituted with saturated heteroalkyl groups which provided a tool compound 9e with excellent PDE10A activity, PDE selectivity, CNS penetrability and with favorable pharmacokinetic profile in rats. Furthermore, the compound 9e was shown to be efficacious in the MK-801 induced psychosis model and in the CAR model of psychosis.
CiteXplore: 24231362