Synthesis and Antioxidant Evaluation of Some New Pyrazolopyridine Derivatives

Abstract

4,6-Dimethyl-1H-pyrazolo[3,4-b]pyridine-3-amine (1) was used as a key intermediate for the synthesis of imidazolopyrazole derivatives 7-11 upon interaction with 3-(2-bromoacetyl)-2H-chromen-2-one (2), 2-(benzothiazol-2-yl)-4-chloro-3-oxobutanenitrile (3), 2,3-dibromonaphthalene-1,4-dione (4), naphtha[2,3-b]oxirene-2,7-dione (5), 2,5-dichloro-3,6-dihydroxyhexa-2,5-diene-1,4-dione (6), respectively. Acetylation of 11 afforded the bis-acetyl 12. Also, the imidazolopyrimidine 15 was prepared via treatment of 1 with sodium 3,4-dioxo-3,4-dihydronaphthalene-1-sulfonate (13) in DMF followed by cyclization of the bis-pyrazolopyrimidine 14 with glacial acetic acid. On the other hand, compound 1 was reacted with (E)-1-(4-methoxyphenyl)-5-(piperidin-1-yl)pent-1-en-3-one hydrochloride (16), 2-hydroxy-3-((piperidin-1-yl)-methyl)-naphthalene-1,4-dione (17), 2-styryl-2H-indene-1,3-dione (18), enaminone 22, chloroquinoline-3-carbaldehyde 27a, chloroquinoline-(6-methyl)-3-carbaldehyde 27b and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (28) to afford pyrazolo[3,4-a]pyrimidines 19-21, 23, 29a, 29b and 30, respectively. Also, the pyrazolopyrimidinone 33 was obtained via treatment of 1 with 1-cyanoacetyl-3,5-dimethylpyrazole (31) followed by cyclization of the formed intermediate 32 with glacial acetic acid. Finally, treatment of 1 with o-terephthalaldehyde in glacial acetic acid afforded diazepine 34. The newly synthesized compounds were screened for their antioxidant properties in which some of them exhibited promising activities. Compounds 1, 14, 15, 23, 26, 29a, 30 and 32 have the ability to protect DNA from the damage induced by bleomycin.

Structural characterization, thermal investigation and biological activity of metal complexes containing Schiff Base ligand (Z)‐3‐(1‐((4,6‐dimethyl‐1H‐pyrazolo[3,4‐b] pyridin‐3‐yl)imino)ethyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one

“…Also, pyrazolo[3,4‐b]pyridines and their derivatives are attractive targets in organic synthesis ascribed to their biological activities such as analgesic, hypnotic, inhibitors of glycogen synthase kinase‐3 (GSK‐3), corticotrophin‐releasing factor (CRF) antagonist, antidiabetic, antiarrhythmic. In addition, they are utilized as anti‐HIV‐1, potential glucocorticoid receptor ligand for positron emission tomography (PET) …”

“…In addition, they are utilized as anti-HIV-1, potential glucocorticoid receptor ligand for positron emission tomography (PET). [39][40][41] 2 | EXPERIMENTAL 2.1 | Material and physical measurements All chemicals used were chemically pure grade and were utilized without further purification. CoCl 2 .6H 2 Elemental analyses (C, H, N) were performed on Perkin Elmer-2400 elemental analyzer at Main Defense Chemical Laboratory.…”

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

“…The reactivity of aminopyrazolopyridine 30 with β-NQSNa (18) for the preparation of 32 with antioxidant properties was investigated by Gouda in 2012 [81]. Intermediate 18 was treated with two equivalents of 30 resulting in bispyrazolopyridine 31, which after treatment with refluxing acetic acid produced imidazopyrazole 32 (Scheme 7).…”

3-(Bromoacetyl)coumarins: unraveling their synthesis, chemistry, and applications

“…Condensation of 3-(bromoacetyl)coumarin 1 with 3-aminopyrazole 70 within DMF/AcOH yielded the corresponding imidazo[1,2- b ]pyrazole 71 ( Scheme 35 ). 91 …”