788134-85-0Relevant academic research and scientific papers
Spiro-substituted piperidines as neurokinin receptor antagonists. II. Syntheses and NK2 receptor-antagonistic activities of N-[2-aryl-4-(spiro- substituted piperidin-1'-yl)butyl]carboxamides
Kubota, Hirokazu,Kakefuda, Akio,Nagaoka, Hitoshi,Yamamoto, Osamu,Ikeda, Ken,Takeuchi, Makoto,Shibanuma, Tadao,Isomura, Yasuo
, p. 242 - 254 (2007/10/03)
In the course of our research on spiro-compounds as neurokinin receptor antagonists, N-[2-aryl-4-spiro-substituted piperidin-1'-yl)butyl]carboxamides were designed, based on YM-35375 (3) as a lead compound, and evaluated for NK2 receptor-antagonistic activities. Some derivatives inhibited the binding of radio-labeled neurokinin A to the NK2 receptor with IC50 values at the level of 10-9. Among these compounds, (±)-1'-[4-(N-benzoyl-N-methylamino)- 3-(3,4-dichlorophenyl)butyl]spiro[benzo[c]thiophene-1(3H), 4'-piperidine] 2- oxide (58, YM-38336) showed 10 times more potent NK2 receptor binding affinity than compound 3 (IC50 values of 8.9 and 84nM, respectively). It showed more potent inhibitory activity (ID50 20μg/kg (i.v.)) against [β- Ala8]-NKA(4 - 10)-induced bronchoconstriction in guinea pigs than compound 3 (ID50 41 μg/kg (i.v.)). This compound was also effective intraduodenally in the same model, exhibiting an ID50 value of 0.41 μg/kg.
