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International Journal of Chemical Studies 2015; 3(3): 46-52
P-ISSN2349–8528
E-ISSN 2321–4902
IJCS 2015; 3(3): 46-52
© 2015 JEZS
Received: 13-08-2015
Accepted: 14-09-2015
Ofentse Mazimba
Botswana Institute for
Technology Research and
Innovation, Private Bag 0082,
Gaborone, Botswana.
Tracy CS Molefe
University of Botswana, Private
Bag 0022, Gaborone, Botswana.
Correspondence:
Ofentse Mazimba
Botswana Institute for
Technology Research and
Innovation, Private Bag 0082,
Gaborone, Botswana.
1, 5-Benzodiazepines: A Review Update
Ofentse Mazimba, Tracy CS Molefe
Abstract
1,5-benzodiazepines are the most studied group of diazepines, which are a class of drugs prescribed
against psychotic disorders. An immense literature is continually produced from the research work
carried out about the synthesis and pharmacological activities of 1,5-benzodiazepine, two recent reviews
in 2013 outlined the importance of this privileged pharmacophore. Due to their wide range of biological
properties the benzodiazepine nucleus has continued to attract many investigators to synthesize and
screen their analogues for all possible activities. This current review article describes the literature
relating to 1,5-benzodiazepines synthetic strategies and provides highlights of the different
pharmacological activities accomplished since 2013.
Keywords: 1,5-Benzodiazepines, Anxiolytic, Synthesis, o-Phenylenediamine, Ketones, Catalyst,
Solvent-free
1. Introduction
Benzodiazepines are an important pharmacophore due to their pharmacotherapeutic properties
and various pharmacopeial information. The 1,5-benzodiazepine nucleus is a privileged
scaffold that is a core structure of medicinal drugs and has received great attention of
medicinal research searching for new derivatives with enhanced pharmacological activities
[1, 2,
3]
. The bicyclic, tricyclic, tetracyclic and fused polycyclic 1,5-benzodiazepines exist in
literature
[4]
. The benzodiazepines have revolutionized the treatment of anxiety and insomnia
since the 1950s with the introduction of chlordiazepoxide
[5]
largely due to their anxiolytic and
sedative-hypnotic effects
[6]
.
The 1,5-benzodiazepine have retained attention due to their pharmacological activities and
immense literature exist on the benzodiazepine nucleus. Bariwal and co-workers
[7]
. Reviewed
the pharmacological profiles of structurally enhanced 1,5-benzodiazepines. Salvi and Mali
[3]
review article reported on the various synthetic routes, solvents and catalysts used towards 1,5-
benzodiazepines and their different pharmacological activities, while another recent review by
Aastha and co-workers
[1]
. Provided an overview of the biological properties and synthetic
schemes for 1,5-benzodiazepine. Casher and co-workers
[8]
. have described benzodiazepines as
versatile clinical tools and a review showing the compendium on genotoxicity and
carcinogenicity data for benzodiazepines drugs appeared in 2007
[9]
.
Post the 2013
[1]
reviews a significant number of articles have appeared in literature reporting
on the synthesis and screening of 1,5-benzodiazepine analogues for all possible activities.
Therefore, this review describes the synthesis of 1,5-benzodiazepine analogues and highlights
the different pharmacological activities from the last two years (2013-2015).
2. Discussion
2.1 The ring system
The IUPAC ring numbering of the simplest form of 1,5-benzodiazepine (2, 3-dihydro-1H-1, 5
benzodiazepine) is shown in Figure 1. The structure has two nitrogen atoms at positions 1 and
5 in a seven membered diazepine ring fused to a benzene ring. The ring system occurs in the
diimine forms where there is conjugation between the two imino groups and the benzene ring,
which bring stability to the system
[10-13]
.
1
3
5
7
5a
9
N
N
Figure 1