Synthesis and substance P receptor binding activity of androstano[3,2-b]pyrimido[1,2-a]benzimidazoles

B R Venepalli; L D Aimone; K C Appell; M R Bell; J A Dority; R Goswami; P L Hall; V Kumar; K B Lawrence; M E Logan

doi:10.1021/jm00080a025

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.

Authors

B R Venepalli¹, L D Aimone, K C Appell, M R Bell, J A Dority, R Goswami, P L Hall, V Kumar, K B Lawrence, M E Logan, et al.

Affiliation

¹ Life Sciences Research Laboratories, Eastman Kodak Company, Rochester, New York 14650-2158.

PMID: 1370695
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