An expedient and facile one-step synthesis of a biguanide library by microwave irradiation coupled with simple product filtration. Inhibitors of dihydrofolate reductase.
It has been demonstrated previously by us that guanide-containing compounds (1 and 2) can inhibit significantly dihydrofolate reductase (DHFR). In this report, we have produced an array of alkyl- and aryl-based biguanide compounds using microwave irradiation. Further, we have demonstrated the use of TMSCl for the first time as an excellent and practical catalyst for the formation of alkyl and aryl biguanides. Using these methods, we prepared a 60-compound collection, of which one compound (21g) showed approximately one-half of the inhibitory activity of the parent compound 2.
Mayer
Stanislas
S
Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3.
Daigle
Denis M
DM
Brown
Eric D
ED
Khatri
Jayantilal
J
Organ
Michael G
MG
D001645:Biguanides / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D004926:Escherichia coli / Q000201:enzymology; D005374:Filtration; D005493:Folic Acid Antagonists / Q000138:chemical synthesis*; D008872:Microwaves; D013762:Tetrahydrofolate Dehydrogenase / Q000187:drug effects*
D001645:Biguanides; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase