Conformationally restricted analogues designed for selective inhibition of GAR Tfase versus thymidylate synthase or dihydrofolate reductase.
The synthesis and evaluation of a series of conformationally restricted analogues of 10-formyl-tetrahydrofolate as potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) or aminoimidazole carboxamide transformylase (AICAR Tfase) are reported.
Boger
D L
DL
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. boger@scripps.edu
Labroli
M A
MA
Marsilje
T H
TH
Jin
Q
Q
Hedrick
M P
MP
Baker
S J
SJ
Shim
J H
JH
Benkovic
S J
SJ
D002460:Cell Line; D002470:Cell Survival; D005493:Folic Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D051026:Phosphoribosylglycinamide Formyltransferase; D013762:Tetrahydrofolate Dehydrogenase / Q000187:drug effects*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D019877:Hydroxymethyl and Formyl Transferases; D051026:Phosphoribosylglycinamide Formyltransferase