1,5‐Benzodiazepine, 2. Mitt.: Entgegengesetzte zentralnervöse Wirkungen der Enantiomere von zwei 3,3‐Dialkyl‐1,5‐benzodiazepin‐2,4‐dionen

Abstract

I.p. applicated S(+)-1, R(-)-1 und rac. 1 prolonged hexobarbital sleeping in rats. The rac. 8-chloro compound 3 given i.p. produced no prolongation. Determination of rac. 1 in serum and tissues of rats 30 min after i.p. administration of 50 mg/kg showed that rac. 1 was detectable in serum and brain, yet its concentration was below the limit of determination. I.v. applicated, the enantiomers of 1 and 3 showed diametrically opposite CNS-effects: The S(+)-enantiomers were convulsively active as pentetrazol, whereas the R(-)-enantiomers were CNS depressant active prolonging hexobarbital sleeping time dose-dependently. High doses of diazepam antagonized dose-dependently the convulsive action of S(+)-1 supporting the hypothesis that this enantiomer acted as a strong inverse agonist, whereas R(-)-1 produced weak agonistic activity at the benzodiazepine binding site of the GABA-receptor.--Enantioselective differences for the binding of the 1-enantiomers to human serum albumin were found, too. R(-)-1 was bound to a greater extent than S(+)-1.

Syntheses of novel 1,5‐benzodiazepinederivatives: Crystal structures, spectroscopic characterizations, Hirshfeld surface analyses, molecular docking studies,DFTcalculations, corrosion inhibition anticipation, and antibacterial activities

“…[19][20][21][22][23] Benzodiazepines (BZD) are classified as drugs known for their remarkable activity on the central nervous system. [24] The area of biological interest of 1,5-benzodiazepines [25] is extended to various diseases such as cancer, [26] viral infection (nonnucleoside reverse transcriptase inhibitors of HIV-1), [27][28][29] and cardiovascular disorders. [27][28][29][30] Indeed, the nucleus 1,5-benzodiazepine is a preferred carrier existing in active compounds belonging to a variety of biological targets such as peptide hormones (Cholecystokinins CCKA and CCKB), [31][32][33] enzymes interleukins ICE, [34][35][36] and potassium inhibitors (Ik) [30] (Scheme 1).…”

A Trifluoroacetic Acid Catalyzed Domino Reaction as an Approach to Amino Acid Derived 2,3-Dihydro-1H-1,5-benzodiazepines

“…1 Among them, benzodiazepines (Figure 1) are widely used in medicinal chemistry. 2 They belong to the class of psychotropics 3 that have notable central nervous system depressant activity, 4 along with various other biologically important activities 5 such as anticancer, 6 antiviral (HIV), 7 and cardiovascular activity. 8 Many members of this family are known as antianxiety, analgesic, antidepressive, sedative, and hypnotic agents 9 and other applications include dyes for acrylic fibers 10 and as anti-inflammatory agents.…”

Bromodimethylsulfonium Bromide (BDMS)-Catalyzed Synthesis of 1,5-Benzodiazepines Using a Multi-Component Reaction Strategy

“…1 Indeed, the concept of 'privileged medicinal structures or scaffolds' was initially coined by Merck researchers during their work on benzodiazepines. 2,3 They exhibit a broad spectrum of pharmacological properties, such as anti-inflammatory, anticonvulsant, anti-anxiety, sedative, antidepressant, hypnotic, 1,4 antibiotic, 5 anticancer 6 and antiviral (HIV) activities, 7 and act as inhibitors of the HIV-1 capsid assembly. 8 Benzodiazepines have been developed as dyes for acrylic fibers 9 and have been used as starting materials for the preparation of triazole 10a and oxadiazole 10b derivatives.…”

“…Unfortunately, the reaction was unsuccessful with aliphatic aldehydes. When the reaction was carried out with cyclohexanecarboxaldehyde, o-phenylenediamine and ethyl acetoacetate, we isolated 2-cyclohexyl-1-(cyclohexylmethyl)-1H-benzo [d]imidazole (5) (see the Supporting Information) in 30% yield, instead of the desired 1,5-benzodiazepine.…”