N-[3-(2-Dimethylaminoethyl)-2-methyl-1H- indol-5-yl]-4-fluorobenzamide: a potent, selective, and orally active 5-HT(1F) receptor agonist potentially useful for migraine therapy

J Med Chem. 2001 Nov 22;44(24):4031-4. doi: 10.1021/jm0155190.

Abstract

Recent studies have demonstrated that selective 5-HT(1F) receptor agonists inhibit neurogenic dural inflammation, a model of migraine headache, indicating that these compounds may be effective therapies for the treatment of migraine pain. This communication describes the synthesis and discovery of a novel compound, N-[3-(2-(dimethylamino)ethyl)-2-methyl-1H-indol-5-yl]-4-fluorobenzamide (4), which possesses high binding affinity and selectivity at the 5-HT(1F) receptor relative to more than 40 other serotonergic and nonserotonergic receptors examined.

MeSH terms

  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / metabolism
  • Benzamides / pharmacology
  • Cell Line
  • Dura Mater / drug effects
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / metabolism
  • Indoles / pharmacology
  • Inflammation
  • Migraine Disorders / drug therapy*
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Rabbits
  • Rats
  • Receptor, Serotonin, 5-HT1F
  • Receptors, Neurotransmitter / metabolism
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Saphenous Vein / drug effects
  • Saphenous Vein / physiology
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Indoles
  • N-(3-(2-dimethylaminoethyl)-2-methyl-1H-indol-5-yl)-4-fluorobenzamide
  • Receptors, Neurotransmitter
  • Receptors, Serotonin
  • Serotonin Receptor Agonists