| Literature DB >> 6127411 |
M Cain, R W Weber, F Guzman, J M Cook, S A Barker, K C Rice, J N Crawley, S M Paul, P Skolnick.
Abstract
We have prepared a series of tetrahydro-beta-carbolines (TH beta C), beta-carbolines (beta-C), and other nitrogen heterocycles and evaluated them in vitro with respect to their ability to bind to benzodiazepine receptors. The fully aromatic beta-C's were more potent than their corresponding TH beta C derivatives. When substituents possessing a carbonyl (CO2Me, COCH3, CHO) were introduced at the beta-C 3-position the in vitro potency was augmented. Alcohol substituents (CH2OH, CHOHCH3) demonstrated decreased in vitro potency. The importance of the carbonyl moiety was further demonstrated when beta-carboline-3-carboxylic acid was shown to bind tighter to benzodiazepine receptors at lower pH. A lower pH increases the concentration of the acid and decreases the concentration of the anion. 3-(Hydroxymethyl)-beta-carboline (24), 3-formyl-beta-carboline (25) and 3-acetyl-beta-carboline (27) were benzodiazepine antagonists in vivo. Methyl isoquinoline-3-carboxylate (31a) also had in vitro activity. The same structure-activity relationships seen in beta-C's were also observed for isoquinolines.Entities:
Mesh：
Substances：
Year: 1982 PMID： 6127411 DOI： 10.1021/jm00351a015
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446