We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Chemical Feature-Based Molecular Modeling of Urotensin-II Receptor Antagonists: Generation of Predictive Pharmacophore Model for Early Drug Discovery.
- Authors
Pandey, Anubhuti; Paliwal, Sarvesh Kumar; Paliwal, Shailendra Kumar
- Abstract
For a series of 35 piperazino-phthalimide and piperazino-isoindolinone based urotensin-II receptor (UT) antagonists, a thoroughly validated 3D pharmacophore model has been developed, consisting of four chemical features: one hydrogen bond acceptor lipid (HBA L), one hydrophobe (HY), and two ring aromatic (RA).Multiple validation techniques like CatScramble, test set prediction, and mapping analysis of advanced known antagonists have been employed to check the predictive power and robustness of the developed model. The results demonstrate that the best model, Hypo 1, shows a correlation (r) of 0.902, a root mean square deviation (RMSD) of 0.886, and the cost difference of 39.69 bits. The model obtained is highly predictive with good correlation values for both internal (r² = 0.707) as well as external (r² = 0.614) test set compounds. Moreover, the pharmacophore model has been used as a 3D query for virtual screening which served to detect prospective new lead compounds which can be further optimized as UT antagonists with potential for treatment of cardiovascular diseases.
- Subjects
UROTENSINS; CHEMICAL inhibitors; DRUG development; PROTOPHILIC solvents; CARDIOVASCULAR diseases
- Publication
Journal of Chemistry, 2014, p1
- ISSN
2090-9063
- Publication type
Article
- DOI
10.1155/2014/921863