Formation of quaternary amines by N-methylation of azaheterocycles with homogeneous amine N-methyltransferases.
Catalytic activities of two amine N-methyltransferases were documented for the following azaheterocycles: isomeric phenyl- and bispyridyls; 2-, 3- and 4-mono-substituted pyridines; and a miscellaneous group of azaheterocycles that included mono- and diazabenzenes and mono- and diazanaphthalenes. The broad substrate specificities of the two amine N-methyltransferases for primary and secondary amines are here extended to a large number of aromatic azaheterocycles in which N-methylation results in the formation of quaternary ammonium metabolites. Pyridine was the best substrate for both enzymes. Substitution in the ring at the 2-position sterically hindered methylation of the pyridyl nitrogen; 2-phenylpyridine and 2,2'-bispyridyl were not substrates.
Crooks
P A
PA
College of Pharmacy, Division of Medicinal Chemistry and Pharmacognosy, University of Kentucky, Lexington 40536-0082.
Godin
C S
CS
Damani
L A
LA
Ansher
S S
SS
Jakoby
W B
WB
D000588:Amines; D000818:Animals; D001372:Aza Compounds / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006571:Heterocyclic Compounds / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D011817:Rabbits; D013379:Substrate Specificity
D000588:Amines; D001372:Aza Compounds; D006571:Heterocyclic Compounds; D011725:Pyridines; D008780:Methyltransferases