Research Article: Synthesis and Pharmacological Valorization of Derivatives of 4-Phenyl-1,5-Benzodiazepin-2-One

Date Published: April 1, 2018

Publisher: Hindawi

Author(s): Terence Nguema Ongone, Redouane Achour, Mostafa El Ghoul, Latifa El Ouasif, Khalid Taghzouti, Meryem El Jemli, Yahia Cherrah, Katim Alaoui, Amina Zellou.


The objective of our work is to make a pharmacological study of molecules derived from 4-phenyl-1,5-benzodiazepin-2-one carrying long chains so that they have a structure similar to surfactants, with the benzodiazepine as a hydrophilic head and a carbon chain as a hydrophobic tail. First, we studied the acute toxicity of the above mentioned 4-phenyl-1,5-benzodiazepin-2-one derivatives. This study was conducted according to OECD 423 guidelines in female mice and revealed that these compounds are nontoxic. We then assessed the psychotropic effects of our products on the central nervous system (CNS). The results obtained show that 4-phenyl-1,5-benzodiazepin-2-one has no sedative effect at therapeutic doses of 100 and 200 mg/kg. On the other hand, its long-chain derivatives possess them. Moreover, all these products have no cataleptic and hypnotic effects at the doses studied. But at 100 mg/kg, these compounds all have the ability to significantly prolong the hypnotic effect of thiopental sodium.

Partial Text

The development of heterocyclic organic chemistry has been very important for humans. Indeed, this part of the chemistry allows the synthesis of bioactive molecules used in the pharmaceutical industry for the preparation of drugs. In this family, benzodiazepines have been shown to be pharmacologically important since they exert anxiolytic, analgesic, anticonvulsant, antidepressant, cataleptic, hypnotic, myorelaxant, and sedative [1–3] effects on the central nervous system (CNS). This is the case of 7-bromo-5-(2-pyridinyl)-1,4-benzodiazepin-2-one (bromazepam) marketed for its strong anxiolytic effect and its effective hypnotic effect [4] and 7-chloro-1-(cyclopropylmethyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one also known as “prazepam” marketed especially for its anxiolytic effect [5]. Other studies report that benzodiazepines have anti-inflammatory, antiviral, anti-HIV, antimicrobial, and antitumor activities [6].

In this work, we have shown that the addition of alkyl chains to 4-phenyl-1,5-benzodiazepin-2-one significantly decreases the acute toxicity of the latter. Indeed, the acute toxicity study conducted by Kanyonga et al. [3] on this compound reveals that its LD50 is 1617.08 mg/kg, whereas our study on its long-chain derivatives 5a–d shows that their respective LD50s are above 2000 mg/kg. This result is in line with the work of Soussan et al. [21].

To conclude, we can say that the pharmacological study that we carried out on 4-phenyl-1,5-benzodiazepin-2-one and its long-chain derivatives 5a–d having a structure similar to surfactants shows that all its products are slightly toxic. Therefore, 5a–d products belong to category V, in the global system of classification of chemical substances.




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