New 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives: Design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents

Khaled R A Abdellatif; Wael A A Fadaly

doi:10.1016/j.bioorg.2017.04.002

New 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives: Design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents

Bioorg Chem. 2017 Jun:72:123-129. doi: 10.1016/j.bioorg.2017.04.002. Epub 2017 Apr 9.

Authors

Khaled R A Abdellatif¹, Wael A A Fadaly²

Affiliations

¹ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; Pharmaceutical Sciences Department, Ibn Sina National College for Medical Studies, Jeddah 21418, Saudi Arabia. Electronic address: khaled.ahmed@pharm.bsu.edu.eg.
² Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.

PMID: 28411407
DOI: 10.1016/j.bioorg.2017.04.002

Abstract

A new series of 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives 10a-h was designed and synthesized for evaluation as selective COX-2 inhibitors, anti-inflammatory agents and as analgesic agents. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compounds 10a, 10b, 10e and 10f were the most COX-2 selective compounds (S.I.=10.76, 10.87, 8.69 and 9.14 respectively), the most potent anti-inflammatory derivatives (ED₅₀=65.7, 60.2, 76.3 and 107.4μmol/kg respectively) in comparison with Celecoxib (COX-2 S.I.=8.61, ED₅₀=82.2μmol/kg) and were less ulcerogenic (ulcer indexes=1.22-3.02) than Ibuprofen (ulcer index=20.25) and comparable to Celecoxib (ulcer index=2.93). The four derivatives (10a, 10b, 10e and 10f) showed considerable analgesic activities which are clearly parallel to their anti-inflammatory activities.

Keywords: Analgesic; Anti-inflammatory; Cyclooxygenase-2 inhibitors; Imidazolone; Oxazolone.

MeSH terms

Analgesics / chemical synthesis
Analgesics / chemistry
Analgesics / pharmacology*
Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Carrageenan
Cattle
Cyclooxygenase 1 / metabolism
Cyclooxygenase 2 / metabolism
Cyclooxygenase Inhibitors / chemical synthesis
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Drug Design
Edema / chemically induced
Edema / drug therapy*
Humans
Imidazoles / chemical synthesis
Imidazoles / chemistry
Imidazoles / pharmacology*
Molecular Structure
Pain / drug therapy*
Pain Measurement
Rats
Structure-Activity Relationship

Substances

Analgesics
Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase Inhibitors
Imidazoles
imidazolone
Carrageenan
Cyclooxygenase 1
Cyclooxygenase 2