Achiral, selective CCK2 receptor antagonists based on a 1,3,5-benzotriazepine-2,4-dione template

Synthesis and Biological Screening of New Derivatives of 2,3-dihydro quinazolin-4(1H)-one and Benzotriazepin- 5(2H)-one for Central Nervous System Activity

“…The rotarod test has demonstrated that compounds IVa, VIb, IVc, and IVd had similar CNS depressant activity and neurotoxicity similar to clozapine while compound VIc had slightly weaker activity. It is observed that table (4) showed that compounds VIb and VIc had strong CNS depressant activity and neurotoxicity as evidenced by the increased percentage of animals that fall from the horizontal screen, while compounds IVa and IVd had slightly weaker effect. In addition, all receiving compound IVc failed to climb to the top of the screen although none of them have fallen of the screen indicating a mild CNS depressant activity and neurotoxicity.…”

“…Proquazone (1) is clinically used as nonsteroidal anti-inflammatory drug 1 , Afloqualone (2) has sedative and muscle relaxant effects 2 and Fenquizone (3) is used primarily in the treatment of edema and hypertension On other hand, Benzotriazepines are mentioned in few literatures in spite of its importance to posses central nervous system 3 and Cholecystokinin (CCK2) antagonist activities 4 . It was reported that compounds (4) and (5) are useful as neuroleptic agents in treatment of schizophrenia [5]and compound (6) found to have the same antipsychotic activity of clozapine 6 .…”

Regioselective synthesis of bicyclic 1,3,5-triazepine system starting from tetrachloro-2-aza-1,3-butadienes

“…Synthesis of cyclopenta[f] [1,3,5]triazepines 5 was performed via interaction of reagents 1 with Nphenyl-1,2-cyclopentadiamine 2. This reaction proceeds in THF at room temperature quite regioselectively and involves electrophilic centre С In such way 4-aryl-2-(dichloromethyl)-1-phenyl-1H,5aH,6H,7H,8H,8aH-cyclopenta[f] [1,3,5]triazepines were prepared and isolated with 92-96% yields.…”

“…1,3,5-Triazepines and their derivatives are found to be associated with various biological activities: antibacterial, antiviral, psychotropic activity, 1,2 CCK2 receptor antagonists, 3 phospholipase A2 inhibitors, 4 HIV capsid assembly inhibitors. 5 However, information about hydrogenated 1,3,5-triazepine derivatives is very limited.…”

“…9,10 Unfortunately, this approach is not adequate for preparation of 1,3,5-triazepines. Previously we proposed to use readily available 1-aryl-1,3,4,4-tetrachloro-2-aza-1,3-butadienes 1 for synthesis [1,3,5]triazepino [1,7-a]benzimidazole derivatives.…”