Synthesis of esters of coenzyme PQQ and IPQ, and stimulation of nerve growth factor production.

Esters of pyrroloquinoline quinone (PQQ), a cofactor of microbial quinoprotein enzyme, and imidazopyrroloquinoline (IPQ, from PQQ and glycine) were synthesized, and their chemical stability, toxicity to L-M cells and nerve growth factor (NGF) inducing activity in L-M cells were studied. PQQ esters were found to be potent enhancers of NGF production, but IPQ esters had only marginal effects on NGF production. The monoester of PQQ with a methoxycarbonyl group at C-2 of PQQ is a most effective compound because of its NGF inducing activity, limited toxicity, safety and chemical stability. These results suggest that PQQ-2-esters could be developed as a curative or preventive drug for retrograde neural diseases in the central and perpheral nervous system.