Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo

Bioorg Med Chem Lett. 1998 Feb 3;8(3):243-8. doi: 10.1016/s0960-894x(98)00020-1.

Abstract

Extensive structural modification of immepyr (+)-2 led to the discovery of trans-4-methyl-3-imidazoyl pyrrolidine (+/-)-3a as a potent and highly selective H3 agonist. The pyrroline (+/-)-3a was resolved, and its (+) enantiomer, Sch 50971 [(+)-3a], showed a greater separation of H3 and H1 activities in vivo (H3/H1 ratio >> 330) than (R)-alpha-methylhistamine (+)-1 (H3/H1 ratio = 17), the standard H3 agonist.

MeSH terms

  • Animals
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / physiology
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology*
  • Receptors, Histamine H3 / drug effects*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 4-methyl-3-imidazoylpyrrolidine
  • Imidazoles
  • Pyrrolidines
  • Receptors, Histamine H3