L. Couper et al., PYRIDINE AND PIPERIDINE-DERIVATIVES AS INHIBITORS OF DIHYDRODIPICOLINIC ACID SYNTHASE, A KEY ENZYME IN THE DIAMINOPIMELATE PATHWAY TO L-LYSINE, Bioorganic & medicinal chemistry letters, 4(19), 1994, pp. 2267-2272
A key step in the diaminopimelate (DAP) pathway to L-lysine (7) involv
es condensation of pyruvate with aspartic acid B-semialdehyde (1) to y
ield L-2,3-dihydrodipicolinic acid (2) (DHDPA) catalyzed by DHDPA synt
hase. The best inhibitors of DHDPA synthase of the thirty pyridine and
piperidine derivatives prepared were the N-oxide (15) of dipicolinic
acid and the di-imidate (13) of dimethyl pyridine-2,6-dicarboxylate ea
ch with an IC50 value of 0.2 mM. The N-oxide (15) and dinitrile (12) a
re non-competitive inhibitors with K-i values of 0.29 and 1.25 mM agai
nst aspartate semialdehyde and 0.06 and 0.34 mM against pyruvate, resp
ectively.