Synthesis and NK1 receptor antagonistic activity of (+/-)-1-acyl-3-(3,4- dichlorophenyl)-3-[2-(spiro-substituted piperidin-1'-yl)ethyl]piperidines.
(+/-)-1-Acyl-3-(3,4-dichlorophenyl)-3-[2-(spiro-substituted piperidin-1'-yl)ethyl]piperidines and their quaternary ammonium salts were prepared and evaluated for their NK1 receptor antagonistic activity. Some of these inhibited SP-induced contraction in guinea pig ileum with IC50 values at a level of 10(-9) M and showed potent inhibitory activity against selective NK1 receptor agonist-induced bronchoconstriction in guinea pigs.
Kubota
H
H
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Okamoto
Y
Y
Fujii
M
M
Ikeda
K
K
Takeuchi
M
M
Shibanuma
T
T
Isomura
Y
Y
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines