Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA)

Bioorg Med Chem Lett. 2004 May 3;14(9):2279-83. doi: 10.1016/j.bmcl.2004.02.014.

Abstract

The synthesis and 5-HT(2A) receptor affinities of ring altered derivatives of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (4), a structurally unique tetracyclic 5-HT(2A) receptor antagonist, are described. The characteristics of the parent compound prove to be necessary for optimal 5-HT(2A) receptor affinity. However, expansion of the size of the pyrrolidine and central rings produce compounds with reasonably high 5-HT(2A) receptor affinities. In addition, the parent compound is shown to have high 5-HT(2) receptor selectivity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Magnetic Resonance Spectroscopy
  • Pyrrolidines / chemistry*
  • Pyrrolidines / metabolism
  • Pyrrolidines / pharmacology*
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT2A / drug effects*
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Spiro Compounds / chemistry*
  • Spiro Compounds / metabolism
  • Spiro Compounds / pharmacology*

Substances

  • Pyrrolidines
  • Receptor, Serotonin, 5-HT2A
  • Spiro Compounds
  • spiro(9,10-dihydroanthracene)-9,3'-pyrrolidine