Synthesis and in vitro evaluation of new diphenyl ether derivatives as serotonin transporter ligands

• 作 者: DEUTHER-CONRAD Winnie BRUST Peter STEINBACH Jrg VERCOUILLIE Johnny
• 机 构: Institute of Interdisciplinary Isotope Research,Institute of Interdisciplinary Isotope Research,Inst
• 出 处: Science in China(Series B:Chemistry)
• 发表日期: 2008年05期
• 关键词: serotonin diphenyl transporter dimethylamino phenoxy fluoro labeled substituent

For the development of new ligands as potential imaging agents for the serotonin transporter (SERT),a series of diphenyl ether derivatives have been synthesized,characterized,and evaluated for their in vitro binding affinities to the SERT. Among the above compounds,2-(2-((dimethylamino)methyl)-4-fluoro-phenoxy)-5-bromobenzenamine (15) and 2-(2-((dimethylamino)methyl)-4-fluorophenoxy)-5-iodobenzene amine (16) show high binding affinities for the SERT with Ki values of 0.28 and 0.20 nmol·L-1,respectively. They can be further labeled with carbon-11,fluorine-18,iodine-123 or bromine-76,and evaluated as useful imaging agents for the SERT. Moreover,the study of the structure-activity relationship (SAR) provides some useful information for the future design of new ligands.

For the development of new ligands as potential imaging agents for the serotonin transporter (SERT), a series of diphenyl ether derivatives have been synthesized, characterized, and evaluated for their in vitro binding affinities to the SERT. (Dimethylamino) methyl) -4-fluoro-phenoxy) -5-bromobenzenamine (15) and 2- (2 dimethylamino) methyl) -4-fluorophenoxy) -5-iodobenzene amine affinities for the SERT with Ki values ​​of 0.28 and 0.20 nmol·L-1, respectively. They could be further labeled with carbon-11, fluorine-18, iodine-123 or bromine-76, and evaluated as useful imaging agents for the SERT Moreover, the study of the structure-activity relationship (SAR) provides some useful information for the future design of new ligands.