Premium
Theoretical approach to the pharmacophoric pattern of GABA B analogs
Author(s) -
Lorenzini M. L.,
BrunoBlanch L.,
Estiú G. L.
Publication year - 1998
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1998)70:6<1195::aid-qua9>3.0.co;2-v
Subject(s) - gabab receptor , chemistry , moiety , molecule , computational chemistry , similarity (geometry) , ab initio , molecular dynamics , stereochemistry , gabaa receptor , receptor , organic chemistry , computer science , biochemistry , artificial intelligence , image (mathematics)
In order to determine the structural requirements that are important for GABA B binding affinity, a quantum‐chemical‐based conformational study has been performed, followed by a similarity analysis which includes 12 GABA B analogs. Due to the flexibility of the structures, a semigrid GABA B analog [2RS‐(5,5‐dimethyl) morpholinyl‐acetic acid] has been used as a template for the amonium moiety in order to help to identify the active conformation. Both in vacuo , and solvent‐simulated calculations, for the physiological media modeled as water molecules, have been compared, for this analog, at ab initio (G94, 6‐31+G(d,p)) and semiempirical (PM3) levels, respectively. On the basis of this comparison, the results of in vacuo PM3 calculations have been chosen for the similarity analysis. We have included, in the calculations, a group of molecules heterogeneous enough to become representative of the different families that can bind to the GABA B receptor site. Following their comparison we report the leading characteristics that can be related to their binding capability and define a pharmacophoric pattern for GABA B analogs. The latter is compared with the one previously found for the binding affinity at the GABA A receptor site. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 1195–1208, 1998