Synthesis and Substance P Receptor Binding Activity of androstano[3,2-b]pyrimido[1,2-a]benzimidazoles

J Med Chem. 1992 Jan 24;35(2):374-8. doi: 10.1021/jm00080a025.

Abstract

Several heterosteroids containing a dihydroethisterone skeleton were prepared and shown to displace substance P in a receptor binding assay. Further biochemical (kinetic and Scatchard analyses) and pharmacological evaluation (substance P-induced plasma extravasation and salivation in the rat) of a representative example in this series (5a) established that these compounds are competitive antagonists at the substance P receptor.

MeSH terms

  • Androstanes / chemical synthesis*
  • Androstanes / metabolism
  • Androstanes / pharmacology
  • Animals
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / metabolism
  • Benzimidazoles / pharmacology
  • Binding, Competitive
  • Brain / metabolism
  • Capillary Permeability / drug effects
  • In Vitro Techniques
  • Male
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Neurokinin-1
  • Receptors, Neurotransmitter / antagonists & inhibitors
  • Receptors, Neurotransmitter / metabolism*
  • Structure-Activity Relationship
  • Substance P / antagonists & inhibitors
  • Substance P / metabolism*

Substances

  • Androstanes
  • Benzimidazoles
  • Receptors, Neurokinin-1
  • Receptors, Neurotransmitter
  • Substance P