Michael Cyclization of Polarized Systems: Synthesis and in vitro Anti-Diabetic Evaluation of Some Novel Pyrimidine, Pyridine, Pyrazole and Pyrazolo[3,4-b ]pyridine Derivatives

Abstract

Various interesting heterocycle skeletons were synthesized via Michael type addition reaction with 1,2; 1,3-bidentate nitrogen and carbon nucleophiles. Cycloaddition of different α,β-unsaturated systems afforded bromopyrimidinone 3/5, bromothiazine 4 and bromopyrazole 6a/6b pyrazole-1-carboxylate 8, pyridinylmethanone 9, nicotinonitrile 10, pyrazolopyridine 11a/11b, pyran-3-carbonitrile 12/13, chromenopyridine 14 and N-butyrylpyrazolyl-1-butanone 15 derivatives. The structures of the synthesized compounds were elucidated based on IR, NMR and mass spectral analyses. Group of the newly synthesized compounds were screened for their anti-diabetic activities, whereas compounds 8 and 11b exhibited promising anti-diabetic activities at micro molar concentration against α-glucosidase inhibitor with IC50 values ranging between 13.80-500 μM. On the other hand compound 10 showed a week effect as compared to the standard anti-diabetic agent.

Structural elucidation, molecular docking, α-amylase and α-glucosidase inhibition studies of 5-amino-nicotinic acid derivatives

“…For the most safe and versatile therapeutic solutions, we diverged into the plethora of naturally occurring medicinal compounds, specifically, nitrogen containing heterocyclic rings. Piperidine, pyridine and pyrimidine derivatives have been known to inhibit carbohydrate digesting enzymes, in addition to their anti-inflammatory, antibacterial and anticancer potencies [13][14][15][16][17][18][19][20].…”

Microwave assisted synthesis of 2-amino-4-chloro-pyrimidine derivatives: Anticancer and computational study on potential inhibitory action against COVID-19

“…Our research group has been working on multifunctional amino derivatives synthesis ( Nawaz et al, 2020 , Rahim etal., 2020, Taha etal., 2020, Gollapalli at al., 2018, Taha et al, 2018 , Ibrahim et al, 2020 ) with antidiabetic and cytotoxic activity ( Qureshi et al, 2020 , Nawaz et al, 2022 ), and for this research we synthesized pyrimidine derivatives. Pyrmidine, a multi therapeutical nitrogen carrying heterocyclic ring, proven against carbohydrate digesting enzymes, bacteria and even cancer cell line ( Taha et al, 2017 , Slyusarenko et al, 1989 , Nawaz et al, 2016 , Soylem et al, 2017 , Altaf et al, 2015 , Krause et al, 2017 , Salar et al, 2017 ) and also many other therapeutic benefits, was selected as parent molecule, to be treated with a variety of functional moieties and the resulting compounds were characterized as per protocol.…”

Facile Synthesis of New 6‐Alkylamino‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile Derivatives

“…), which are constructed from two fused pyrazole and pyridine rings. Among them, pyrazolo[3,4‐ b ] pyridine core I has been relatively of more interest because of reported interesting biological properties such as antidiabetic , antiproliferative , antifungal , anticancer , antibacterial , anti‐inflammatory , antiviral , and antimalarial activities. Some of them have also inhibitory activities against fibroblast growth factor receptor kinase , TNF‐α , IL‐6 , CDK1 , and glycogen synthase kinase‐3 .…”