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It is now well accepted that at least some serotonin receptors exist in dimeric and oligmeric forms. The linking of receptor ligands has been shown to have potential in the development of selective agonists and antagonists for traditionally refractive receptors. Here we report the development of a dimeric version of the known 5-HT(2A)R antagonist, M-100907. Derivatives of M-100907 were synthesized to determine an appropriate site for the linker connection. Then, homodimers with polyether linkers of different lengths were functionally tested in a bioassay to determine the optimal linker length. Attachment at the catechol of M-100907 with linkers between 12 and 18 atoms in length proved to be optimal.

Synthesis and Evaluation of Dimeric Derivatives of 5-HT2A Receptor (5-HT2AR) Antagonist M-100907

Synthesis and Evaluation of Dimeric Derivatives of 5-HT_2A Receptor (5-HT_2AR) Antagonist M-100907