Document Report Card

ID: ALA3243948

Journal: J Med Chem

Title: Vitamin B6 antagonists obtained by replacing or modifying the 2-methyl group.

Authors: Korytnyk W, Angelino N.

Abstract: The 2-methyl group of pyridoxol was replaced with various other groups, including 2-amino and 2-methylamino as examples of electron-donating substituents and including 2-carboxyl, 2-carboxamide, and 2-halo as examples of electron-withdrawing substituents. The key intermediate in the synthesis was 3-O-benzyl-alpha4,alpha5-O-isopropylidene-alpha2-pyridoxol (15) or the corresponding 2-aldehyde (2). Another approach for modifying the 2 position, but chemically less successful, started with 3-O-methylpyridoxol, which was oxidized to the tricarboxylic acid, decarboxylated, esterfied, and reduced with LiAlH4, providing derivatives in which the 2-CH3 group was replaced with H. The analogues were tested for their growth-inhibitory activity against mouse mammary adenocarcinoma cells in culture. The 2-azine, 2-chloro, and 2-amino analogues were active as inhibitors at ID50 approximately or equal to 10(-5) M, whereas the 2-fluoro and 2-carboxylic acid analogues were inactive at 1 X 10(-4) M. The results are contrasted with those found earlier for similar modifications in other positions of the vitamin B6 molecule. Although the 2-chloro analogue was found to inhibit pyridoxal phosphokinase (KI=24 micron), the 6-chloro analogue was inactive as an inhibitor at 1 mM.

CiteXplore: 559765

DOI: 10.1021/jm00216a002