Synthesis and biological evaluation of NK1 antagonists derived from L-tryptophan

…, KJ Merchant, S Sadowski, S Hardwicke…

Index: MacLeod, Angus M.; Cascieri, Margaret A.; Merchant, Kevin J.; Sadowski, Sharon; Hardwicke, Sarah; et al. Journal of Medicinal Chemistry, 1995 , vol. 38, # 6 p. 934 - 941

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Citation Number: 30

Abstract

The 3, 5-bis (trifluoromethyl) benzyl ester of N-acetyl-L-tryptophan (31, which was derived from the screening lead N-ethyl-L-tryptophan benzyl ester, has been used as a starting point to identify high-affinity substance P receptor antagonists with improved in vivo activity. Altering the ester moiety to an amide or ether led to a substantial loss in binding affinity, but conversion to a ketone provided compounds with affinity comparable to the equivalent ...