Synthesis and substance P receptor binding activity of androstano[3,2-b]pyrimido[1,2-a]benzimidazoles.
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.
Life Sciences Research Laboratories, Eastman Kodak Company, Rochester, New York 14650-2158.
B R
BR
Venepalli
L D
LD
Aimone
K C
KC
Appell
M R
MR
Bell
J A
JA
Dority
R
R
Goswami
P L
PL
Hall
V
V
Kumar
K B
KB
Lawrence
M E
ME
Logan
D000731:Androstanes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000731:Androstanes; D001562:Benzimidazoles; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P