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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. March 2005, Volume 4, Number 3, 210-220 |
QSAR Study on Some Ethenesulfonamide Derivatives as Endothelin Receptor Antagonists
Shovanlal Gayen, Bikash Debnath, Anindya Basu, Soma Samanta, Balaram Ghosh, Sudip Kumar Naskar, and Tarun Jha
Internet Electron. J. Mol. Des. 2005, 4, 210-220
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Abstract:
QSAR study has been carried out on some ethenesulfonamide
derivatives for their ETA and ETB receptor antagonism. E-state
indices of common atoms and the physicochemical parameters of
the substituents were used to find out the essential substitition
pattern required for selectivity of this type of compounds towards
endothelin receptor. Correlation Analysis and Multiple Linear
Regression (MLR) Analysis have been carried out to derive the
best QSAR models. The best QSAR models obtained separately
for endothelin receptor antagonistic activity (pETBIC50 and
pETAIC50 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 ETB 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 ETA antagonism. Presence of di- or tri-substitution
in the phenyl ring (X) further confers selectivity to
these compounds. The study reveals the importance of atom level
topological index in identifying atoms and fragments, which are
necessary for biological activity.
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