Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes.

Autor: Sagar SR; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Ahmedabad, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India; Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India., Agarwal JK; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Ahmedabad, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India., Pandya DH; Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India., Dash RP; Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India., Nivsarkar M; Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India., Vasu KK; Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India. Electronic address: kamalav@perdcentre.com.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Oct 15; Vol. 25 (20), pp. 4428-33. Date of Electronic Publication: 2015 Sep 08.
DOI: 10.1016/j.bmcl.2015.09.015
Abstrakt: We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amongst all the synthesized compounds, 6-methyl-5-(4-methylpyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (5k) was found to be the most active based on in vitro DPP-IV studies and also exhibited promising in vivo blood glucose lowering activity in male Wistar rats.
(Copyright © 2015. Published by Elsevier Ltd.)
Databáze: MEDLINE
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