Synthesis and biological properties of alpha-mono- and alpha-difluoromethyl derivatives of tryptophan and 5-hydroxytryptophan.
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.
Schirlin
D
D
Merrell Dow Research Institute, Strasbourg Center, France.
Gerhart
F
F
Hornsperger
J M
JM
Hamon
M
M
Wagner
J
J
Jung
M J
MJ
D006916:5-Hydroxytryptophan / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D000596:Amino Acids; D002395:Catecholamines; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D005459:Fluorides