Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3): A target for heart failure and platelet aggregation

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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37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6010-6015
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number18
DOIs
StatePublished - Sep 15 2012

Keywords

  • 2-Pyridone derivatives
  • Baylis-Hillman acetates
  • Docking studies
  • Enamines
  • Leads
  • PDE3 inhibition

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    Ravinder, M., Mahendar, B., Mattapally, S., Hamsini, K. V., Reddy, T. N., Rohit, C., Srinivas, K., Banerjee, S. K., & Rao, V. J. (2012). Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3): A target for heart failure and platelet aggregation. Bioorganic and Medicinal Chemistry Letters, 22(18), 6010-6015. https://doi.org/10.1016/j.bmcl.2012.05.019