K. S. Andronati, E. Kostenko, T. Karaseva
Jul 1, 2002
Citations
0
Influential Citations
5
Citations
Journal
Pharmaceutical Chemistry Journal
Abstract
As is known, 3-amino-1,2-dihydro-3H-1,4-benzodiazepin-2-one derivatives produce anxiolytic, anticonvulsant, anorexigenic, analgesic, and other effects. The pharmacological properties of these compounds are mostly related to their ability to bind to benzodiazepine receptors and to cholecystokinin receptors of the two types, CCK1 and CCK2 [1]. Some of these derivatives (devazepide, L-365,260, L-736,380, etc.) are now in various states of clinical testing as potential drugs for the treatment of alimentary obesity and anxiety and panic states of various etiology [2, 3]. In order to study the relationship between the structure of substituted 1,2-dihydro-3H-1,4-benzodiazepin-2-ones and their psychopharmacological and anorexigenic properties, we synthesized a series of new N-substituted 3-amino-5aryl-7-bromo-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (I) (Table 1). Compounds Ia – Id were obtained via interaction of 3-chloro-7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzodiazepin -2-ones (II) with diethylamine, 1,6-diaminohexane, or p-nitroaniline. Compounds Ie and If, containing the -aminobutyric acid (GABA) residue in position 3 of the benzodiazepine nucleus, were synthesized by reaction between GABA methyl ester hydrochloride with 3-chlorobenzodiazepines II in the presence of triethylamine, followed by alkaline hydrolysis of the intermediate esters III. The proposed structures of new compounds were confirmed by IR spectroscopy and mass spectrometry.