Molecular Design QSAR Study on Some Ethenesulfonamide Derivatives as Endothelin Receptor Antagonists BioChem Press QSAR Study on Some Ethenesulfonamide Derivatives as Endothelin Receptor Antagonists

Shovanlal Gayen, Bikash Debnath, Anindya Basu, Soma Samanta, Balaram Ghosh, Sudip Kumar Naskar, Tarun Jha, S Gayen, B Debnath, A Basu, S Samanta, B Ghosh (+9 others)
2005 Internet Electronic Journal of Molecular Design   unpublished
Motivation. QSAR study has been carried out on some ethenesulfonamide derivatives for their ET A and ET B receptor antagonism. Estate indices of common atoms and the physicochemical parameters of the substituents were used to find out the essential substitution pattern required for selectivity of this type of compounds towards endothelin receptor. Method. Correlation Analysis and Multiple Linear Regression (MLR) Analysis have been carried out to derive the best QSAR models. Results. The best
more » ... esults. The best QSAR models obtained separately for endothelin receptor antagonistic activity (pET B IC 50 and pET A IC 50 as well as log Sel) have correlation coefficients 0.854, 0.820 and 0.864 respectively. These models describe that substitution pattern at phenyl ring (X) is an important contributor to the antagonism of selective endothelin receptor. Hydrophobicity of the p-substituents of the phenyl ring (X) has advantageous effect for the selective action on the ET B receptor. Decrease of molar refractivity of the p-substituents and presence of p-methyl group in the phenyl ring (X) have advantageous effect to selective ET A antagonism. Presence of di-or tri-substitution in the phenyl ring (X) further confers selectivity to these compounds. Conclusions. The study reveals the importance of atom level topological index in identifying atoms and fragments, which are necessary for biological activity.