4-Alkylpiperidines related to SR-48968: potent antagonists of the neurokinin-2 (NK2) receptor

Bioorg Med Chem Lett. 1998 Jul 21;8(14):1935-40. doi: 10.1016/s0960-894x(98)00037-7.


A series of 4-alkylpiperidine derivatives related to the potent neurokinin-2 (NK2) receptor antagonist SR-48968 (1) is described. Simple aliphatic derivatives were found to be poorly active, but appropriate placement of an alcohol functional group afforded compounds that were of similar activity to 1. Several representatives in this series, such as the 4-(1-hydroxy-1-ethylpropyl)piperidine (14), were found to exhibit oral activity in a model of labored abdominal breathing in guinea pigs. These results expand the latitude of substituents available in this region of this series of NK2 receptor antagonists.

MeSH terms

  • Animals
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Guinea Pigs
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Receptors, Neurokinin-2 / antagonists & inhibitors*


  • Benzamides
  • Piperidines
  • Receptors, Neurokinin-2
  • SR 48968