N-Phenyl-3-Pyridin-2-yl Imino Derivatives as Vascular Smooth Muscle Relaxants: Potential Phosphodiesterase V Inhibitors

Abstract

The present communication deals with development of ten novel N-Phenyl-3-Pyridin-2-yl imino derivatives as vascular smooth muscle relaxants. The derivatives were prepared and optimized using pocket modelling and pharmacophore modelling. The 4 hydroxy substituted derivatives are showed potent activity comparable to the sildenafil. native ligand surface were marked. The marked pocket of the protein was used for optimizing structural requirements of designed molecules and further studies. Docking Studies. To explore the interactions of the com- pounds, we carried out binding simulations using biopredicta module of Vlife MDS 4.3 suite. We used the crystal structure of the Phosphodiesterase V PDB ID 2H42, to perform dock- ing simulations and potential H-bonding, π-stacking, VDW, Hydrophobic interactions with the designed compounds were recorded. The structure of 3,4-thiadiazol-2-yl)-3-((5- nitropyridin-2-yl)imino)butanamide was used as the tem- plate to built the molecules in the dataset in builder module of Vlife MDS 4.3. Prior to docking studies a systematic conformational search was performed to obtain the low energy conformations of the ligands. The low energy confor- mations thus obtained, were optimized till they reached rms gradient energy of 0.001 kcal/mol A. In order to define ligand-receptor interactions, docking of all the low energy conformations within a range of 5 kcal/mol A from the lowest energy conformation of each molecule. Molecular Alignment. 13 The molecules of the dataset