Synthesis and structure of 3-arylidene and 3-hetarylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones and their affinity toward CNS benzodiazepine receptors

Pavlovsky, V. I.; Bachinskii, S. Yu.; Ткачук, Н. А.; Makan, S. Yu.; Андронати, С. А.; Simonov, Yu. A.; Филиппова, Ирина; Gdaniec, Мaria

doi:10.1007/s10593-007-0161-3

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…In addition, Pavlovsky et al previously described the arrangement of 3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-one in dimers due to the N(1)-HÁÁÁO(2) hydrogen bonds [12]. On another hand, the 2-aminopyridine also revealed a great tendency to develop intermolecular hydrogen bonding [13,14].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of novel O-alkylbenzochromeno-1,5-benzodiazepinones. Study of the N–H····N and CO····HN hydrogen bonding interactions with 2-aminopyridines

Nsira

Gharbi

Msaddek

2014

Comptes Rendus. Chimie

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A series of novel 6-(O-alky)lbenzochromeno-1,5-benzodiazepin-2-ones 4a-c was prepared through the condensation between the [1]benzopyrano [4,3-c][1,5]benzodiazepin-7(8H)one 1 and a series of alkylalcohols. Scaffold 4 exhibited interesting hydrogenbonding interaction with 2-aminopyridine derivatives. The so obtained self-assembled systems 5 were fully characterized by 1D/2D-NMR techniques and mass spectrometry. The hydrogen-bonding interaction was supported by IR and Raman spectroscopy and by 1 H NMR titration experiments, and was confirmed by an X-ray crystal structure analysis.

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Section: Resultsmentioning

confidence: 99%

Synthesis of novel O-alkylbenzochromeno-1,5-benzodiazepinones. Study of the N–H····N and CO····HN hydrogen bonding interactions with 2-aminopyridines

Nsira

Gharbi

Msaddek

2014

Comptes Rendus. Chimie

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“…Синтез та властивості 3-ариліден-1,2-дигідро-3Н-1,4-бензодіазепін-2-онів 11-18 були описані раніше в роботах [9][10][11]. Синтез відбувався в умовах модифікованої реакції Кневенагеля.…”

Section: матеріали і методи дослідженняunclassified

“…Ці дані збігаються з наявними у літературі даними про вплив положення атомів хлору і брому у 3-бензиліденовому радикалі молекули 1,4-бензодіазепін-2-ону на афінітет до TSPO рецепторів ЦНС [9]. Виявлено, що основним структурним фрагментом, що визначає тропність зв'язування 3-бензиліден-похідних з TSPO рецепторами є наявність у пара-положенні бензиліденового фрагменту електронегативних замісників:…”

Section: пара-фтор >>орто-фтор > мета-фторunclassified

Synthesis and Properties of New 1-Hydrazinocarbonylmethyl-7-Bromo-5-Phenyl-3-Arylydene-1,2-Dihydro-3h-1,4-Benzodiazepin-2-Ones

Bachinsky,

Burenkova,

Andronati

et al. 2023

Вісник ОНУ

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It is known that 1,4-benzodiazepines have neurotropic properties. Previously, we synthesized a series of 3-arylidene-1,2-dihydro-3H-1,4-benzdiazepin-2-ones 11-18 and showed that they exhibit significant analgesic activity. They also show significant affinity for central benzodiazepine receptors and TSPO receptors CNS. With this in mind, we have previously modified the series of 3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones by alkylation of 3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones with monobromoacetic acid methyl ester to the first position of the 1,4-diazepine ring to obtain 1-methoxycarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 19-26, which showed pronounced analgesic activity. The aim of this work is to synthesize and study the affinity for CBR and TSPO receptors 1-hydrazinocarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 27-31, which have not been previously described in the literature. Compounds 27-31 were synthesized as a result of the reaction of 1-methoxycarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 19-26 with hydrazine hydrate while stirring the components in ethanol. The yields of the reaction products were 65-92%. It was shown that the hydrazinolysis technique used provides high yields of the target compounds. The structure of the synthesized compounds was confirmed by mass spectrometry and 1H NMR spectroscopy. The affinity of the synthesized compounds to the central benzodiazepine receptors CNS (CBR) and TSPO receptors CNS was studied. The affinity of compounds 27-31 was determined in vitro by radioligand analysis by their ability to displace the commercial radioligands [3H] flumazenil and [3H]PK11195 from their specific binding sites in the GABAA receptor complex and TSPO receptors of the synaptic and the mitochondrial fractions of the rat brain membranes, respectively. Compound 27 displaces the commercial [3H]flumazenil radioligand from its specific binding sites in the GABAA receptor complex by 80.1%, and simultaneously exhibits a very low affinity for TSPO receptors. Derivative 27 is the most potent CBR ligand among the investigated compounds and it is a promising compound for pharmacological research. It has been established that in the synthesized series of 3-fluorobenzylidene derivatives, varying the position of the fluorine atom in the benzylidene fragment leads to change affinity for TSPO receptors. It has been established that the para- position of the fluorine atom in the 3-benzylidene radical of the 1,4-benzodiazepin-2-one molecule is the most important descriptor that determines their affinity for the TSPO receptors. These data agree with the data available in the literature on the effect of the position of chlorine and bromine atoms in the 3-benzylidene radical of the 1,4-benzodiazepin-2-one molecule on the affinity for the TSPO receptors. It was found that the main structural fragment that determines the affinity of binding of 3-benzylidene derivatives to TSPO receptors is the presence of electronegative substituents in the para-position of the benzylidene fragment: para–Hal>>оrtho–Hal>meta–Hal (affinity for TSPO) (Hal= Br, F) Thus, the expediency of further study of this class of compounds is shown.

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“…V. I. Pavlovsky et al . reported that 3‐arylidene and 3‐hetarylidene 1,4‐diazepine derivatives afford good affinity toward central nervous system benzodiazepine receptors .…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Characterization of 1, 3‐disubstituted‐1,4‐benzodiazepine Derivatives

Ghelani

Naliapara

2015

Journal of Heterocyclic Chem

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The 2‐amino‐4′‐flouro‐benzophenone (1) that was reacted with chloroacetylchloride to afford 2‐chloro‐N‐(2‐(4′‐fluorobenzoyl) phenyl)acetamide (2) was subsequently converted to 1,4‐benzodiazepines (3) by the modification of the known hexamethylenetetramine based cyclization reaction developed by Blazevic and Kajfez. Thus, obtained product (3) was reacted with a variety of alkyl halide using KOH in DMF to give 1‐substituted‐5‐(4‐fluorophenyl)‐1H‐benzo[e][1,4]diazepin‐2(3H)‐one (4a, 4b). To achieve 1, 3‐disubstituted 1, 4‐benzodiazepines (5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l, 5m, 5n, 5o, 5p, 5q, 5r, 5s, 5t), 1‐substituted‐5‐(4‐fluorophenyl)‐1H‐benzo[e][1,4]diazepin‐2(3H)‐one (4a, 4b) was treated with various aromatic aldehydes in the presence of KOH in toluene.

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Synthesis and structure of 3-arylidene and 3-hetarylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones and their affinity toward CNS benzodiazepine receptors

Cited by 4 publications

References 9 publications

Synthesis of novel O-alkylbenzochromeno-1,5-benzodiazepinones. Study of the N–H····N and CO····HN hydrogen bonding interactions with 2-aminopyridines

Synthesis of novel O-alkylbenzochromeno-1,5-benzodiazepinones. Study of the N–H····N and CO····HN hydrogen bonding interactions with 2-aminopyridines

Synthesis and Properties of New 1-Hydrazinocarbonylmethyl-7-Bromo-5-Phenyl-3-Arylydene-1,2-Dihydro-3h-1,4-Benzodiazepin-2-Ones

Design, Synthesis, and Characterization of 1, 3‐disubstituted‐1,4‐benzodiazepine Derivatives

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