新型吡唑并嘧啶酮类作为糖尿病中DPP-IV抑制剂的设计、合成及生物学评价
Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes.
作者信息
Sagar Sneha R, Agarwal Jessica K, Pandya Dhaivat H, Dash Ranjeet Prasad, Nivsarkar Manish, Vasu Kamala K
机构信息
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.
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Ahmedabad, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India.
出版信息
Bioorg Med Chem Lett. 2015 Oct 15;25(20):4428-33. doi: 10.1016/j.bmcl.2015.09.015. Epub 2015 Sep 8.
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.
我们报道了一系列新型吡唑并[3,4 - d]嘧啶酮作为糖尿病中DPP - IV抑制剂的设计、合成、生物活性和对接研究。合成了这些分子并评估了它们的DPP - IV抑制活性。发现化合物5e、5k、5o和6a是DPP - IV酶的有效抑制剂。在所有合成的化合物中，基于体外DPP - IV研究，6 - 甲基 - 5 - (4 - 甲基吡啶 - 2 - 基) - 1 - 苯基 - 1H - 吡唑并[3,4 - d]嘧啶 - 4(5H) - 酮(5k)被发现是活性最高的，并且在雄性Wistar大鼠中也表现出有前景的体内降血糖活性。
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