title: Synthesis of Novel Substituted Thiourea and Benzimidazole Derivatives Containing a Pyrazolone Ring as Anti-Inflammatory Agents.
abstract: Two series of new 1-(alkyl/aryl)-3-{2-[(5-oxo-4,5-dihydro-1H-pyrazol-3-yl)amino]phenyl}thioureas 2a-h and 5-[2-(substituted amino)-1H-benzimidazol-1-yl]-4H-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.
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Moneer
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
authors.forename: Khaled O
authors.initials: KO
authors.lastname: Mohammed
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
authors.forename: Hala B
authors.initials: HB
authors.lastname: El-Nassan
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry*; D047069:Pyrazolones / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D047069:Pyrazolones; C038362:pyrazolone; D013890:Thiourea
keywords: COX inhibitors; anti-inflammatory activity; benzimidazole; pyrazolone; thiourea