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• W1969130118 endingPage "1383" @default.
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• W1969130118 abstract "We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the α3 receptor subtype with 5-fold selectivity in binding affinity over α1. This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the α3 subtype over the α1 subtype was 12-fold (for 57). Although most analogues showed no selectivity in terms of efficacy, some did show partial agonism at α1 and antagonism at α3 (e.g., 25 and 75). However, two analogues tested (93 and 96), both with triazole substituents in the 6-position, showed significantly higher efficacy for the α3 subtype over the α1 subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series." @default.
• W1969130118 created "2016-06-24" @default.
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• W1969130118 date "2005-02-04" @default.
• W1969130118 modified "2023-10-14" @default.
• W1969130118 title "Discovery of Functionally Selective 7,8,9,10-Tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-<i>a</i>]phthalazines as GABA_A Receptor Agonists at the α₃ Subunit" @default.
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• W1969130118 doi "https://doi.org/10.1021/jm040883v" @default.
• W1969130118 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15743180" @default.
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