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Synthesis of Novel Substituted Thiourea and Benzimidazole Derivatives Containing a Pyrazolone Ring as Anti‐Inflammatory Agents
Author(s) -
Moneer Ashraf A.,
Mohammed Khaled O.,
ElNassan Hala B.
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12712
Subject(s) - chemistry , benzimidazole , pyrazolone , diclofenac , anti inflammatory , thiourea , cyclooxygenase , in vivo , docking (animal) , stereochemistry , enzyme , pharmacology , biochemistry , organic chemistry , medicine , biology , microbiology and biotechnology , nursing
Two series of new 1‐(alkyl/aryl)‐3‐{2‐[(5‐oxo‐4,5‐dihydro‐1 H ‐pyrazol‐3‐yl)amino]phenyl}thioureas 2a – h and 5‐[2‐(substituted amino)‐1 H ‐benzimidazol‐1‐yl]‐4 H ‐pyrazol‐3‐ols 3a – i were designed and synthesized as anti‐inflammatory agents. The cyclooxygenase inhibitory activity of the newly synthesized compounds was investigated. All the compounds showed non‐selective inhibition of COX ‐1 and COX ‐2 enzymes which was consistent with their docking results. Compounds 2c , 2f , 2g , 3b , and 3g that showed the highest COX ‐2 inhibitory activity were selected for further in vivo testing as anti‐inflammatory agents using diclofenac as a reference drug. Two of the test compounds ( 2c and 3b ) showed potent anti‐inflammatory activity comparable to that of diclofenac with lower ulcerogenic effect relative to indomethacin. SAR study of the two series as cyclooxygenase inhibitors and anti‐inflammatory agents was also provided.