Design, synthesis, cyclooxygenase inhibition and biological evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing amino/methanesulfonyl pharmacophore

被引：22

作者：

Abdellatif, Khaled R. A. ^{[1
]}

Fadaly, Wael A. A. ^{[1
]}

机构：

[1] Beni Suef Univ, Dept Organ Pharmaceut Chem, Bani Suwayf 62514, Egypt

来源：

BIOORGANIC CHEMISTRY | 2017年 / 70卷

关键词：

Anti-inflammatory; 1,3,5-Triaryl-4,5-dihydro-1H-pyrazole; Cyclooxygenase-2; inhibitors; POTENTIAL ANTIINFLAMMATORY AGENTS; SELECTIVE COX-2 INHIBITORS; ULCEROGENIC LIABILITY; CELECOXIB; ROFECOXIB; ANALOGS;

D O I：

10.1016/j.bioorg.2016.11.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole 10a-l was designed and synthesized via cyclization of chalcones 8a-f with 4-amino/methanesulfonylphenylhydrazine hydrochloride 9a-b. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity, ulcerogenic liability and analgesic activity. All compounds were more COX-2 inhibitors than COX-1. While most compounds showed good anti-inflammatory activity, the trimethoxy derivatives (10a, 10b, 10g and 10h) were the most potent derivatives (ED50 = 55.78, 53.99, 67.65 and 69.20 mu mol/kg respectively) in comparison with celecoxib (ED50 = 82.15 mu mol/kg). Compounds 10a, 10b, 10g and 10h (ulcer index = 2.68, 1.20, 2.63 and 2.66 respectively) showed less ulceration effect than celecoxib (ulcer index = 2.90). Also, Compounds 10a, 10b, 10g and 10h showed analgesic activity higher than celecoxib and comparable to that of ibuprofen. In addition, molecular docking studies were performed for compounds 10a, 10b, 10g and 10h and the results were in agreement with that obtained from the in vitro COX inhibition assays. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：57 / 66

页数：10

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