Abstract:
: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.
journal_name
Arch Pharm (Weinheim)journal_title
Archiv der Pharmazieauthors
De Luca L,Gitto R,Barreca ML,Caruso R,Quartarone S,Citraro R,De Sarro G,Chimirri Adoi
10.1002/ardp.200600022subject
Has Abstractpub_date
2006-07-01 00:00:00pages
388-400issue
7eissn
0365-6233issn
1521-4184journal_volume
339pub_type
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