C4 phenyl aporphines with selective h5-HT(2B) receptor affinity

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3451-4. doi: 10.1016/j.bmcl.2015.07.012. Epub 2015 Jul 11.

Abstract

A group of aporphine alkaloids related to (±)-nantenine (1) and bearing a C4 phenyl and various C1 or N-substituents, was synthesized and evaluated for affinity to h5-HT receptors. In general, unlike nantenine, the analogs lack affinity for the h5-HT(2A) receptor and other 5-HT receptors but bind selectively to the h5-HT(2B) receptor. With regards to 5-HT(2B) affinity, there appears to be a low tolerance for bulky C1 or N-substituents when the C4 phenyl moiety is present. Compound 5a had the highest 5-HT(2B) affinity of the compounds tested, was found to be an antagonist and is selective vs other CNS receptors.

Keywords: 5-HT(2A); 5-HT(2B); Aporphine; CNS; Nantenine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aporphines / chemistry*
  • Aporphines / pharmacology
  • Molecular Structure
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Serotonin 5-HT2 Receptor Antagonists / chemistry*
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Aporphines
  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Antagonists
  • nantenine