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

doi:10.1016/j.bmcl.2012.05.019

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

Genetics, Cell Biology and Development (TMED)

Research output: Contribution to journal › Article › peer-review

46 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 language	English (US)
Pages (from-to)	6010-6015
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2012.05.019
State	Published - Sep 15 2012

Bibliographical note

Funding Information:
The authors thank the Director, IICT and Project Director, NIPER-Hyderabad for encouragement. This work is the Main Lab Project of IICT. S.K.B. thank DBT ( BT/HRD/35/02/09/2008 ). M.R. thanks CSIR, New Delhi and B.M., T.N.R. thank UGC New Delhi, S.M. thank ICMR, New Delhi for research fellowships.

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

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

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10.1016/j.bmcl.2012.05.019

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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

Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3) : A target for heart failure and platelet aggregation. / Ravinder, Mettu; Mahendar, Budde; Mattapally, Saidulu; Hamsini, Kommi Venkata; Reddy, Thatikonda Narendar; Rohit, Chilappa; Srinivas, Kolupula; Banerjee, Sanjay Kumar; Rao, Vaidya Jayathirtha.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 18, 15.09.2012, p. 6010-6015.

Research output: Contribution to journal › Article › peer-review

Ravinder, M, Mahendar, B, Mattapally, S, Hamsini, KV, Reddy, TN, Rohit, C, Srinivas, K, Banerjee, SK & Rao, VJ 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, vol. 22, no. 18, pp. 6010-6015. https://doi.org/10.1016/j.bmcl.2012.05.019

Ravinder, Mettu ; Mahendar, Budde ; Mattapally, Saidulu ; Hamsini, Kommi Venkata ; Reddy, Thatikonda Narendar ; Rohit, Chilappa ; Srinivas, Kolupula ; Banerjee, Sanjay Kumar ; Rao, Vaidya Jayathirtha. / Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3) : A target for heart failure and platelet aggregation. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 18. pp. 6010-6015.

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

Abstract

Bibliographical note

Keywords

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