|
Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. July 2007, Volume 6, Number 7, 183-199 |
Search for Structural Requirements of 2-Phenylimidazo[1,2-α]pyridineacetamide
Analogs to Improve Affinity and Selectivity towards Central and/or
Peripheral Benzodiazepine Receptors
Soma Samanta, Parthasarathi Panda, Sk. Mahasin Alam, and Tarun Jha
Internet Electron. J. Mol. Des. 2007, 6, 183-199
|
Abstract:
Central benzodiazepine receptors (CBRs) and peripheral benzodiazepine
receptors (PBRs) are benzodiazepine receptors present in the brain. These
receptors play valuable roles in calcium flow, cell proliferation, cellular
immunity, cellular respiration, malignancy, muscle relaxation and sedation.
2-Phenylimidazo[1,2-α]pyridineacetamide analogs are potent and selective ligands
for CBRs and PBRs. An attempt is made to find out the required structural
features responsible for high affinity and selectivity of
2-phenylimidazo[1,2-α]pyridineacetamide analogs towards CBRs or PBRs through
computational design.
A QSAR study of 37 analogs of 2-phenylimidazo[1,2-α]pyridineacetamide was
performed using topological and quantum chemical descriptors. Correlation and
multiple regression analyses were performed to develop QSAR models. The present
study showed that some atoms played important roles in electronic and
hydrophobic interactions with central benzodiazepine receptors (CBRs) for
improving affinity and selectivity of these compounds. Atomic charges of some
atoms, dipole moment, total energy as well as the presence of acetamide group
and double substitution on carboxamide nitrogen favor the high affinities and
selectivities of PBRs. The QSAR models developed in this study are used to
generate a possible mapping of the pharmacophore. The QSAR equations explain
the importance of particular atoms/groups for CBRs or PBRs affinity. The
presence of a chlorine atom at ‘Y’ is favorable to the CBRs affinity whereas
the presence of an acetamide group and disubstitution on carboxamide nitrogen
favor PBRs affinity.
|