Design and synthesis of 1,3-diarylurea derivatives as selective cyclooxygenase (COX-2) inhibitors

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• 作者：Afshin Zarghi ; Samaneh Kakhgi ; Atefeh Hadipoor ; Bahram Daraee ; Orkideh G. Dadrass ; Mehdi Hedayati
• 关键词：1 ; 3-Diarylurea ; COX-2 inhibition ; SAR
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 出版时间：15 February 2008
• 年：2008
• 卷：18
• 期：4
• 页码：1336-1339
• 全文大小：235 K

文摘

A group of 1,3-diarylurea derivatives, possessing a methylsulfonyl pharmacophore at the para-position of the N-1 phenyl ring, in conjunction with a N-3 substituted-phenyl ring (4-F, 4-Cl, 4-Me, 4-OMe), were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1/COX-2 isozyme inhibition structure–activity studies identified 1-(4-methylsulfonylphenyl)-3-(4-methoxyphenyl) urea (4e) as a potent COX-2 inhibitor (IC₅₀ = 0.11 μM) with a high COX-2 selectivity index (SI = 203.6) comparable to the reference drug celecoxib (COX-2 IC₅₀ = 0.06 μM; COX-2 SI = 405). The structure–activity data acquired indicate that the urea moiety constitutes a suitable scaffold to design new acyclic 1,3-diarylurea derivatives with selective COX-2 inhibitory activity.