Aza-tricyclic substance P antagonists.
The synthesis and structure-activity relationships of a series of aza-tricyclic analogs of the quinuclidine substance P (SP) antagonist 1 are described. The SP receptor affinity of these compounds was found to vary according to the size of the new ring fused to the quinuclidine and the mode of fusion. Correlations between receptor affinity and (1) the steric bulk of the newly introduced ring fusion and (2) the dihedral angle between the benzhydryl and benzylamino substituents of these aza-tricyclic compounds were explored.
Lowe
J A
JA
Central Research Division, Pfizer, Inc., Groton, Connecticut 06340.
Drozda
S E
SE
McLean
S
S
Bryce
D K
DK
Crawford
R T
RT
Snider
R M
RM
Longo
K P
KP
Nagahisa
A
A
Tsuchiya
M
M
D000818:Animals; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D011812:Quinuclidines / Q000138:chemical synthesis / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000037:antagonists & inhibitors*; D014513:Ureter / Q000187:drug effects
D001952:Bridged-Ring Compounds; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D013373:Substance P