title: Synthesis and pharmacological properties of new derivatives of 4-methyl-5-oxalo-1H-2,3,4,5-tetrahydro-1,5-benzodiazepin-2-one and beta-oxo-5-(4-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepin-2 -one)propionic acid.
abstract: 5-Ethoxalyl 4-methyl-1H-2,3,4,5-tetrahydro 1,5-benzodiazepin-2 -one [I] and 5-ethoxymalonyl-4-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepi n-2-one [IV] were subjected to transesterification using alcohols (propanol, butanol, pentanol) giving derivatives II-IV, VII, VIII. The derivatives I and VI were caused to undergo ammonolysis giving 4-methyl-5-oxamoyl-1H-2,3,4,5 tetrahydro 1,5-benzodiazepin-2-one [V] and 5-malonamoyl-4-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepin++ +-2-one [IX]. The compounds I-IX were tested towards their psychotropic activity. The preparates I, III and V had an anxiolytic action in the four-plate test. The anxiolytic properties of the compound V were confirmed in the test of the black-white box. The antagonism of all investigated compounds for toward reserpine, first of all of the preparations III, IV, V and IX, indicates an antidepressive activity dependent on a stimulation of the adrenergic system.
authors.affiliation: Department of Technology of Drugs, Wrocław University of Medicine, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Nawrocka
authors.forename: M
authors.initials: M
authors.lastname: Rutkowska
authors.forename: A
authors.initials: A
authors.lastname: Szelag
authors.forename: J
authors.initials: J
authors.lastname: Barczyńska
authors.forename: L
authors.initials: L
authors.lastname: Kedzierska-Goździk
authors.forename: F
authors.initials: F
authors.lastname: Błaszczyk
authors.forename: W
authors.initials: W
authors.lastname: Dziwiszek
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis*; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones