Premium
3D Pharmacophore Models for 1,2,3,4‐Tetrahydroisoquinoline Derivatives Acting as Anticonvulsant Agents
Author(s) -
De Luca Laura,
Gitto Rosaria,
Barreca Maria Letizia,
Caruso Roberta,
Quartarone Silvana,
Citraro Rita,
De Sarro Giovambattista,
Chimirri Alba
Publication year - 2006
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200600022
Subject(s) - pharmacophore , chemistry , anticonvulsant , stereochemistry , quantitative structure–activity relationship , hydrogen bond , potency , tetrahydroisoquinoline , ampa receptor , combinatorial chemistry , molecular model , receptor , molecule , glutamate receptor , organic chemistry , biochemistry , in vitro , psychology , neuroscience , epilepsy
A 3D pharmacophore model predicting anticonvulsant activity was obtained for a series of 6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline derivatives recently disclosed as a new class of noncompetitive AMPA receptor antagonists. The training set included 17 compounds with varying potency against audiogenic seizures in DBA/2 mice. The best statistical hypothesis, generated with the HypoGen module of Catalyst 4.9, consisted of five features: two hydrogen bond acceptors, two hydrophobic features, and one hydrophobic aromatic region, providing a model with a correlation coefficient of 0.919. The obtained model was an efficient tool in the design of some new anticonvulsant agents containing the tetrahydroisoquinoline scaffold. Moreover, in order to explain the different degree of efficacy of the newly designed N ‐substituted derivatives, excluded volumes were also considered.