148700-88-3Relevant academic research and scientific papers
N-heteroaryl-2-phenyl-3-(benzyloxy)piperidines: A novel class of potent orally active human NK1 antagonists
Ladduwahetty,Baker,Cascieri,Chambers,Haworth,Keown,MacIntyre,Metzger,Owen,Rycroft,Sadowski,Seward,Shepheard,Swain,Tattersall,Watt,Williamson,Hargreaves
, p. 2907 - 2914 (1996)
The preparation of a series of N-heteroarylpiperidine ether-based human NK1 antagonists is described. Two of the compounds (3-[{(2S,3S)-3-(((3,5- bis(trifluoromethyl)phenyl)methyl)oxy)-2-phenylpiperidino}methyl ]-1,2,4- triazole (11) and 5-[{(2S,3S)-3-(((3,5- bis(trifluoromethyl)phenyl)methyl)oxy)-2-phenylpiperidino}methyl ]-3-oxo- 1,2,4-triazolone (12)), in particular, are orally bioavailable and exhibited significant improvements in potency, both in vitro and in vivo, over the lead (carboxamidomethyl)piperidine ether 1. Rat liver microsome studies on a selected number of compounds from this series show the triazolone heterocycle to be considerably more stable than the others. Furthermore, both 11 and 12 have been profiled in a number of assays that may be predictive of the clinical utility of substance P antagonists.
