title: Triazolines 26: 1-Aryl-5-amido-1,2,3-triazolines, a new group of triazoline anticonvulsants. Effect of 5-substitution on anticonvulsant activity.
abstract: Studies in our laboratories have led to the discovery of the delta 2-1,2,3-triazolines as a unique family of anticonvulsant agents hitherto unknown. The anticonvulsant activity of 1,5-diaryl- and 1-aryl-5-pyridyltriazolines was previously reported; this paper describes the evaluation of two series of 1-aryl-5-amido-1,2,3-triazolines, A and B, where the 5-amido groups are (2-oxo-1-pyrrolidino)- (1-8) and (N-methyl-N-acetamido)- (9-15), respectively. The 1-aryl-5-(2-oxo-1-pyrrolidino)-1,2,3-triazolines of the A series, which are uniquely substituted with the pyrrolidinone lactam ring, a cyclic gamma-aminobutyric acid (GABA) structure, seem to function by enhancing inhibitory GABAergic mechanisms. Radioligand binding studies for the two most active triazolines 2 and 7, indicate that both compounds strongly inhibit the specific binding of [3H]GABA to GABAB receptor sites, with Ki = 1.7 and 0.91 microM respectively. The anticonvulsant activity among the various groups of triazolines studied so far appears to be dependent on the 5-substituent groups: 4-pyridyl- >> 2-oxo-1-pyrrolidino- > N-methyl-N-acetamido- > 3-pyridyl > or = aryl approximately 2-pyridyl > 2-quinolyl.
authors.affiliation: Division of Medicinal Chemistry and Pharmaceutics, University of Kentucky, Lexington 40536-0082, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Kadaba
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology*; D018756:GABA Antagonists; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D018756:GABA Antagonists; D014230:Triazoles