PMID: 7513763Apr 29, 1994Paper

Identification of L-tryptophan derivatives with potent and selective antagonist activity at the NK1 receptor

Journal of Medicinal Chemistry
A M MacleodE Ber

Abstract

As part of a program of screening the Merck sample collection, N-ethyl-L-tryptophan benzyl ester was identified as a weak antagonist at the substance P (NK1) receptor. Structure-activity studies showed that the indole ring system could be replaced by 3,4-dichlorophenyl, alpha- or beta-naphthyl, or benzthiophene with retention or only small loss of affinity. It was found that acylation of the tryptophan nitrogen gave compounds with higher affinity than N-ethyl or other basic amines. Optimization of substitution on the benzyl ester led to the identification of the 3,5-bis-(trifluoromethyl)benzyl ester of N-acetyl-L-tryptophan 26 as a potent and selective substance P receptor antagonist. Compound 26 blocked substance P induced dermal extravasation in vivo and was the most potent compound from this structurally novel class of antagonists which further adds to the diversity of small molecules that bind to the (NK1) receptor.

Citations

Jun 23, 2005·Journal of Biomedical Science·Yi-Ruu LinMing-Huan Chan
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·H QiM MaCcoss
Nov 22, 2002·Journal of the American Society for Mass Spectrometry·Gianluca GiorgiFabio Ponticelli
Mar 8, 2014·World Journal of Gastroenterology : WJG·Miguel Muñoz, Rafael Coveñas
Aug 2, 2001·The Journal of Pharmacy and Pharmacology·R MilletJ P Hénichart
Sep 14, 2018·Current Medicinal Chemistry·Charlene Gadais, Steven Ballet
Nov 24, 1999·Journal of Applied Physiology·J B MorrisG Gianutsos
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Sep 1, 1996·Pharmazie in unserer Zeit·F Eiden, H Lentzen
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Dec 19, 1996·Chemical Reviews·George A. Patani, Edmond J. LaVoie
Jul 19, 1996·Journal of Medicinal Chemistry·T LadduwahettyR J Hargreaves

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