Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1-phenylpyrazolo[3,4-d]pyrimidine derivatives

Abstract

A new group of 1-phenylpyrazolo [3,4-d]pyrimidine derivatives 14a-d-21 were synthesized from 2-(6-methyl-1-phenyl-1H-pyrazolo [3,4-d]pyrimidin-4-yloxy)acetohydrazide (12). All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, antiinflammatory activity and ulcerogenic liability. All the target compounds were more potential in inhibiting COX-2 than COX-1. Compounds having pyrazolyl moiety in a hybrid structure with pyrazolo[3,4-d]pyrimidine scaffold (14a-d, 16 and 17) showed higher edema inhibition percentage activities (34-68%) and the 5-aminopyrazole derivative (14c, ED 50 ¼ 87.9 mmol/kg) was the most potent one4celecoxib (ED 50 ¼ 91.9 mmol/kg). While, the in vivo potent compounds (14a-d, 16, 17 and 21) caused variable ulceration effect (ulcer index ¼ 0.33-4.0) comparable to that of celecoxib (ulcer index ¼ 0.33), the pyrazol-3-one derivative (16) and the acetohydrazide (21) were the least ulcerogenic derivatives showing the same ulcerogenic potential of celecoxib.

New indomethacin analogs as selective COX‐2 inhibitors: Synthesis, COX‐1/2 inhibitory activity, anti‐inflammatory, ulcerogenicity, histopathological, and docking studies

“…The ulcerogenic effect of the most COX‐2 selective compounds, 4b , 4d , 5 , and 6 , which also showed a high percentage of edema inhibition, was evaluated according to a previous study (Table 3). [ 29 ]…”

“…The ulcerogenic liability of the most active compounds that showed an effective in vivo anti‐inflammatory activity was evaluated according to a previous study. [ 29 ] Rats were fasted one day before drug administration and divided into eight separate groups (each group with six rats). All compounds were dissolved in 1% Tween in saline and administrated orally.…”

Design, Synthesis and Biological Evaluation of 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles and their Derivatives as Analgesic Agents

“…Fipronil, a member of 5-aminopyrazole family, is the most effective pesticide as it blocks the GABA-gated, glutamate-gate chloride channels and disrupts the central nervous system of insects. Interestingly, ethyl 5-amino-1-(2-(6-methyl-1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-yloxy)acetyl)-1H-pyrazole-4-carboxylate [18] and 5-amino-1-(2-fluorophenyl)-N-(5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl-1H-pyrazole-4-carboxamide [19] are reported in the literature as an anti-inflammatory agent.…”

Novel synthesis of pyrazole-containing thiophene, 2-alkyloxy-pyridine and thieno[2,3-d]pyrimidine scaffolds as analgesic agents

“…Moreover, pyrazole-based heterocycles as thiophenes, 2-alkyloxypyridines and thieno [2,3-d]pyrimidines have been given more attention due to their useful therapeutic fields including, muscle relaxing, antitumor, anti-depressant, antimicrobial, antidiabetic, antitubercular, antioxidant, HIV reverse transcriptase inhibitors and also possess significant vasodilation activities [11][12][13][14][15][16][17]. They also demonstrated strong anti-inflammatory action with low GIT toxicity and analgesic impacts [18][19][20][21][22][23][24]. In the same way, and in the continuing work on synthesis of biologically active heterocycles based pyrazoles [25][26][27][28][29], we focused in this study on designing of new molecules carrying pyrazole substituents as hybrids with various heterocycles aiming to get potent candidates with analgesic properties.…”