6‐Nitroazolo[1,5‐a]pyrimidin‐7(4H)‐ones as Antidiabetic Agents

Abstract

Prevention of the formation of advanced glycation end-products (AGEs) is a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In these terms, new synthetic approaches to 6-nitroazolo[1,5-a]pyrimidines have been developed on the basis of the promising antiglycation activity of their structural analogues, such as azolo[5,1-c][1,2,4]triazine-4(1H)-ones. A number of nitroazolopyrimidines were obtained by using nitration, chlorodeoxygenation, and amination reactions, and their antidiabetic properties were elucidated in vitro. It was shown that triazolo[1,5-a]pyrimidine-7(4H)-ones exhibit a higher antiglycation activity than the corresponding 7-alkylamino analogs and aminoguanidine, as the reference compound. It is suggested that this kind of activity can be associated with the chelating properties possessed by the synthesized 6-nitro-7-oxoderivatives. Furthermore, the compounds obtained were tested for their inhibitory activity against dipeptidyl peptidase 4 (DPP4), glycogen phosphorylase, and α-glucosidase in vitro, but their activities proved to be significantly inferior to those of the reference compounds.

Pyrimido[1,2-a]benzimidazoles: synthesis and perspective of their pharmacological use

“…It is known that nitroazolopyrimidines and their derivatives possess useful biological activity. 33,[131][132][133][134][135] In addition, the presence of such an important structural fragment as the nitro group seems to be promising from the point of view of further transformations, for example, in the creation of polycyclic purine-like structures. 136…”

A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure–Activity Relationship

“…Pyrimidine is a heteroaryl system that consists of nitrogen at the first and third positions. In recent years, pyrimidine has gained focus for its use in many diseases as they have been used as antiviral ( Rashad and Ali, 2006 ; Rashad et al, 2009 ; Perlíková and Hocek, 2017 ; Wang et al, 2018 ), anticancer ( Galmarini et al, 2003 ; Song et al, 2011 ; Perlíková and Hocek, 2017 ), anti-hypertensive ( El-Hamouly et al, 2006 ; Ismail et al, 2006 ), anti-mycobacterial ( Garg et al, 2016 ; Khandazhinskaya et al, 2018 ), anti-microbial ( Okasha et al, 2016 ; Beyzaei et al, 2017 ; Marepu et al, 2018 ), anti-diabetic ( Spasov et al, 2017 ; Fang et al, 2018 ) and anti-inflammatory activities ( Zhang et al, 2017 ; Abdelgawad et al, 2018 ) .…”

Discovery of Nitro-azolo[1,5-a]pyrimidines with Anti-Inflammatory and Protective Activity against LPS-Induced Acute Lung Injury

“…We have shown that this class possesses a wide range of antiviral actions [ 18 , 19 ] and an affinity toward adenosine receptors [ 20 ] that is associated with improved survival in LPS-induced septic shock [ 21 ]. Furthermore, some derivatives of this heterocycle series demonstrated higher antiglycation activity than a reference compound, aminoguanidine, and could be considered candidates for extended studies to produce drugs against complications of diabetes mellitus [ 22 , 23 ]. Additionally, it was shown that nitro-derivatives of this series demonstrate low toxicity [ 17 ], which is uncommon for nitro-compounds.…”