TY - JOUR
T1 - Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3)
T2 - A target for heart failure and platelet aggregation
AU - Ravinder, Mettu
AU - Mahendar, Budde
AU - Mattapally, Saidulu
AU - Hamsini, Kommi Venkata
AU - Reddy, Thatikonda Narendar
AU - Rohit, Chilappa
AU - Srinivas, Kolupula
AU - Banerjee, Sanjay Kumar
AU - Rao, Vaidya Jayathirtha
N1 - 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.
PY - 2012/9/15
Y1 - 2012/9/15
N2 - 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.
AB - 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.
KW - 2-Pyridone derivatives
KW - Baylis-Hillman acetates
KW - Docking studies
KW - Enamines
KW - Leads
KW - PDE3 inhibition
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U2 - 10.1016/j.bmcl.2012.05.019
DO - 10.1016/j.bmcl.2012.05.019
M3 - Article
C2 - 22897945
AN - SCOPUS:84865491180
SN - 0960-894X
VL - 22
SP - 6010
EP - 6015
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 18
ER -
