title: Synthesis and evaluation of dimeric derivatives of 5-HT(2A) receptor (5-HT(2A)R) antagonist M-100907.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Center for Addiction Research, The University of Texas Medical Branch, 301 University Blvd. Galveston, TX 77555-0615.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Shashack
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Cunningham
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Seitz
authors.forename: Andrew
authors.initials: A
authors.lastname: McGinnis
authors.forename: Thressa
authors.initials: T
authors.lastname: Smith
authors.forename: Cheryl S
authors.initials: CS
authors.lastname: Watson
authors.forename: Scott R
authors.initials: SR
authors.lastname: Gilbertson