Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3): A target for heart failure and platelet aggregation |
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Authors: | Mettu Ravinder Budde Mahendar Saidulu Mattapally Kommi Venkata Hamsini Thatikonda Narendar Reddy Chilappa Rohit Kolupula Srinivas Sanjay Kumar Banerjee Vaidya Jayathirtha Rao |
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Affiliation: | Organic Chemistry Division II, Indian Institute of Chemical Technology, Uppal Road Tarnaka, Hyderabad 500607, India. |
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Abstract: | Twenty-six 2-pyridone derivatives (8a-8z), which are structurally analogous to amrinone and milrinone two important cardiotonic drugs, are synthesized and characterized. The synthesis of 2-pyridone derivatives involves addition, followed by cyclization between Baylis-Hillman acetates (7a-7k) and enamino esters or nitriles (3a-3e). Thus synthesized pyridones were subjected to PDE3 inhibitory activity, 14 pyridones were found to be hits out of 26 pyridones synthesized and out of 14 hits, there are 5 pyridones found to be lead compounds having excellent PDE3 inhibitory activity. Further we have carried out computational analysis to understand protein/enzyme and 2-pyridone derivative interactions to identify amino acid residues involved in the vicinity of binding and compared with milrinone drug. |
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