Synthesis and biological properties of .alpha.-mono and .alpha.-difluoromethyl derivatives of tryptophan and 5-hydroxytryptophan
- 1 January 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (1) , 30-36
- https://doi.org/10.1021/jm00396a007
Abstract
The syntheses of .alpha.-mono- and .alpha.-difluoromethyl derivatives of tryptophan and 5-hydroxytryptophan are described. In an attempt to selectively regulate serotonin synthesis, .alpha.-(mono- and difluoromethyl)tryptophan were tested in vivo as precursors (or prodrugs) of their 5-hydroxy analogues. Although .alpha.-(mono- and difluoromethyl)-5-hydroxytryptophans are potent irreversible inhibitors of aromatic amino acid decarboxylase (equipotent to .alpha.-difluoromethyl-Dopa), only .alpha.-(monofluoromethyl)tryptophan affects the level of serotonin in vivo (small decrease), .alpha.-(difluoromethyl)tryptophan being a very poor substrate of the activating (or helper) enzyme, tryptophan hydroxylase.This publication has 0 references indexed in Scilit: