New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine

Bioorg Med Chem. 2011 Oct 1;19(19):5861-8. doi: 10.1016/j.bmc.2011.08.019. Epub 2011 Aug 18.

Abstract

A series of C1, C2, C3 and N6 analogs of nantenine (2) was synthesized and evaluated in 5-HT(2A) and α(1A) receptor functional assays. Alkyl substitution of the C1 and N6 methyl groups of nantenine provided selective 5-HT(2A) and α(1A) antagonists, respectively. The C2 alkyloxy analogs studied were generally selective for α(1A) versus 5-HT(2A). The C3 bromo analog 15 is one of the most potent aporphinoid 5-HT(2A) antagonists known presently.

Publication types

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

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / chemical synthesis
  • Adrenergic alpha-1 Receptor Antagonists / chemistry*
  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Aporphines / chemical synthesis
  • Aporphines / chemistry*
  • Aporphines / pharmacology
  • Receptor, Serotonin, 5-HT2A / chemistry*
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptors, Adrenergic, alpha-1 / chemistry*
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Serotonin 5-HT2 Receptor Antagonists / chemical synthesis
  • Serotonin 5-HT2 Receptor Antagonists / chemistry*
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology
  • Structure-Activity Relationship

Substances

  • 3-bromonantenine
  • Adrenergic alpha-1 Receptor Antagonists
  • Aporphines
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Adrenergic, alpha-1
  • Serotonin 5-HT2 Receptor Antagonists
  • nantenine