Synthesis and biological activity of 3-[2-(dimethylamino)ethyl]-5-[(1,1-dioxo-5-methyl-1,2,5-thiadiazolidin- 2-yl)-methyl]-1H-indole and analogues: agonists for the 5-HT1D receptor

J Med Chem. 1994 Sep 16;37(19):3023-32. doi: 10.1021/jm00045a006.

Abstract

A novel series of 5-(1,1-dioxo-1,2,5-thiadiazolidin-2-yl)tryptamines was designed, synthesized, and evaluated as 5-HT1D receptor agonists. Compounds such as 8d,f,k were identified which had comparable affinity, potency, and receptor selectivity to that of the antimigraine drug sumatriptan. Both 8d,k were found to be well absorbed in the rat with oral bioavailabilities of 66% and 62%, respectively. Additionally, 8d was found to be selective over other non-serotonergic receptors and exhibited relatively low central nervous system penetration.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Drug Stability
  • In Vitro Techniques
  • Indoles / chemical synthesis*
  • Indoles / metabolism
  • Indoles / pharmacology*
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Rabbits
  • Saphenous Vein / drug effects
  • Saphenous Vein / physiology
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / metabolism
  • Serotonin Receptor Agonists / pharmacology*
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis*
  • Thiadiazoles / metabolism
  • Thiadiazoles / pharmacology*
  • Tryptamines / chemical synthesis*
  • Tryptamines / metabolism
  • Tryptamines / pharmacology*

Substances

  • Indoles
  • Serotonin Receptor Agonists
  • Thiadiazoles
  • Tryptamines