4, 4-Disubstituted piperidine high-affinity NK1 antagonists: structure-activity relationships and in vivo activity

…, M Kurtz, T Ladduwahetty, KJ Merchant…

Index: Stevenson, Graeme I.; Huscroft, Ian; MacLeod, Angus M.; Swain, Christopher J.; Cascieri, Margaret A.; Chicchi, Gary G.; Graham, Michael I.; Harrison, Timothy; Kelleher, Fintan J.; Kurtz, Marc; Ladduwahetty, Tamara; Merchant, Kevin J.; Metzger, Joseph M.; MacIntyre; Sadowski, Sharon; Sohal, Balbinder; Owens, Andrew P. Journal of Medicinal Chemistry, 1998 , vol. 41, # 23 p. 4623 - 4635

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Citation Number: 28

Abstract

Previously reported studies from these laboratories described the design of a novel series of high-affinity NK1 antagonists based on the 4, 4-disubstituted piperidine ring system. Further structure-activity studies have now established that for high NK1 affinity the benzyl ether side chain must be 3, 5-disubstituted and highly lipophilic, the optimal side chain being the 3, 5- bis (trifluoromethyl) benzyl ether, 12 (hNK1 IC50= 0.95 nM). Additional studies have ...