Synthesis of phenylpiperazine derivatives of 1,4-benzodioxan as selective COX-2 inhibitors and anti-inflammatory agents

• Published in: Bioorganic & medicinal chemistry 2016-11, Vol.24 (21), p.5626-5632
• Main Authors: Sun, Juan, Wang, Su, Sheng, Gui-Hua, Lian, Zhi-Min, Liu, Han-Yu, Zhu, Hai-Liang
• Format: Article
• Language: English
• Subjects: 1,4-Benzodioxan; Animals; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-inflammatory scaffold; Carrageenan; Catalytic Domain - drug effects; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2; Dioxanes - chemistry; Dioxanes - pharmacology; Dose-Response Relationship, Drug; Edema - chemically induced; Edema - drug therapy; Humans; Male; Mice; Molecular Docking Simulation; Molecular Structure; Phenylpiperazine; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Rats; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2016.09.023

Compound 3k maybe a new anti-inflammatory lead-candidate as powerful and novel non-ulcerogenic. [Display omitted] 1-((2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-4-substituted-phenylpiperazine moiety was prepared and has been found to be a new and selective ligand for the enzyme cyclooxygenase-2 (COX-2). The biological activity of compound 3k as anti-inflammatory agent was further investigated both in vitro and in vivo. Notably, compound 3k exhibited the best anti-inflammatory activity among the eleven designed compounds with no toxicity, as determined by the ulcerogenic activity. Computational docking studies also showed that compound 3k has interaction with COX-2 key residues in the active site. Compound 3k maybe a new anti-inflammatory lead-candidate as powerful and novel non-ulcerogenic.