Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593319 | Bioorganic & Medicinal Chemistry Letters | 2013 | 8 Pages |
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.
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Authors
Abhisek Banerjee, Lakshminarayana Narayana, Firoj A. Raje, Dnyandeo V. Pisal, Pradip A. Kadam, Srinivas Gullapalli, Hemant Kumar, Sandeep V. More, Malini Bajpai, Ramachandra Rao Sangana, Satyawan Jadhav, Girish S. Gudi, Neelima Khairatkar-Joshi,