Using a drug discovery scheme for Alzheimer's disease (AD) that is based upon multiple pathologies of old age, we identified a potent compound with efficacy in rodent memory and AD animal models.  Since this compound, J147 , is a phenyl hydrazide, there was concern that it can be metabolized to one or more aromatic amines/hydrazines that are potentially carcinogenic.  To explore this possibility, we examined the metabolites of J147  in human and mouse microsomes and mouse plasma.  It was found that J147  is not metabolized to aromatic amines or hydrazines, that the scaffold is exceptionally stable, and that the oxidative metabolites are neuroprotective in a manner similar to the parent compound.  It is concluded that the metabolites of J147  are likely safe and may contribute to its biological activity in animals.

Metabolism of a potent neuroprotective hydrazide

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.