Design and synthesis of novel, potent and selective hypoxanthine analogs as adenosine A1 receptor antagonists and their biological evaluation

Publication date: Available online 16 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Summon Koul, Vidya Ramdas, Dinesh A. Barawkar, Yogesh B. Waman, Neela Prasad, Santosh Kumar Madadi, Yogesh D. Shejul, Rajesh Bonagiri, Sujay Basu, Suraj Menon, Srinivasa B. Reddy, Sandhya Chaturvedi, Srinivas Rao Chennamaneni, Gaurav Bedse, Rhishikesh Thakare, Jayasagar Gundu, Sumit Chaudhary, Siddhartha De, Ashwinkumar V. Meru, Venkata Palle, Anita Chugh, Kasim A. Mookhtiar
Multipronged approach was used to synthesize a library of diverse C-8 cyclopentyl hypoxanthine analogs from a common intermediate III. Several potent and selective compounds were identified and evaluated for pharmacokinetic (PK) properties in Wistar rats. One of the compounds 14 with acceptable PK parameters was selected for testing in in-vivo primary acute diuresis model. The compound demonstrated significant diuretic activity in this model.

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