Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
A number of analogues of the low-efficacy partial GABAA agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL), in which the 4-position of the 3-isoxazolol ring is substituted by different groups, were synthesized and tested as GABAA receptor ligands. While alkyl and benzyl substitution provided affinities and antagonist potencies comparable to those of 4-PIOL, diphenylalkyl and naphthylalkyl substitution resulted in marked increase in both affinity and potency. The 2-naphthylmethyl and the 3,3-diphenylpropyl analogues showed antagonist potencies comparable or markedly higher than that of the standard antagonist SR 95531. Molecular modeling studies exposed a large cavity in the vicinity of the 4-position of 4-PIOL, in which there seems to be additional sites for specific receptor interactions.
Originalsprog | Engelsk |
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Tidsskrift | European Journal of Medicinal Chemistry |
Vol/bind | 38 |
Udgave nummer | 4 |
Sider (fra-til) | 447-449 |
Antal sider | 3 |
ISSN | 0223-5234 |
DOI | |
Status | Udgivet - 1 apr. 2003 |
ID: 244649911