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.
Bibliographical noteFunding 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.
- 2-Pyridone derivatives
- Baylis-Hillman acetates
- Docking studies
- PDE3 inhibition