4-ALKYLPIPERIDINES RELATED TO SR48968 - POTENT ANTAGONISTS OF THE NEUROKININ-2 (NK2) RECEPTOR

A series of 4-alkylpiperidine derivatives related to the potent neurok inin-2 (NK2) receptor antagonist SR-48968 (1) is described. Simple ali phatic derivatives were found to be poorly active, but appropriate pla cement 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 pig s. These results expand the latitude of substituents available in this region of this series of NK2 receptor antagonists. (C) 1998 Elsevier Science Ltd. All rights reserved.