ISSN:
0020-7608
Keywords:
GABAB analogs
;
pharmacophoric pattern
;
molecular similarity
;
quantum chemical calculations
;
Chemistry
;
Theoretical, Physical and Computational Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
In order to determine the structural requirements that are important for GABAB binding affinity, a quantum-chemical-based conformational study has been performed, followed by a similarity analysis which includes 12 GABAB analogs. Due to the flexibility of the structures, a semigrid GABAB 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 GABAB receptor site. Following their comparison we report the leading characteristics that can be related to their binding capability and define a pharmacophoric pattern for GABAB analogs. The latter is compared with the one previously found for the binding affinity at the GABAA receptor site. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 1195-1208, 1998
Additional Material:
9 Ill.
Type of Medium:
Electronic Resource
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