Author/Editor		Poe, Michael M.; Methuku, Kashi Reddy; Li, Guanguan; Verma, Ashwini R.; Teske, Kelly A.; Stafford, Douglas C.; Arnold, Leggy A.; Cramer, Jeffrey W.; Jones, Timothy M.; Černe, Rok
Title		Synthesis and characterization of a novel gamma-aminobutyric acid type A (GABA A ) receptor ligand that combines outstanding metabolic stability, pharmacokinetics, and anxiolytic efficacy
Type		članek
Vol. and No.		Letnik 59, št. 23
Publication year		2016
Volume		str. 10800-10806
ISSN		0022-2623 - Journal of medicinal chemistry
Language		eng
Abstract		1,4-Benzodiazepines are used in the treatment of anxiety disorders but have limited long term use due to adverse effects. HZ-166 ( 2 ) has been shown to have anxiolytic-like effects with reduced sedative/ataxic liabilities. A 1,3-oxazole KRM-II-81 ( 9 ) was discovered from a series of six bioisosteres with significantly improved pharmacokinetic and pharmacodynamic properties as compared to 2 . Oxazole 9 was further characterized and exhibited improved anxiolytic-like effects in a mouse marble burying assay and a rat Vogel conflict test
Keywords		anxiety disorders 1,4-Benzodiazepines pharmacokinetics anksiozne motnje 1,4-benzodiazepini farmakokinetika