Neurotoxins and Drugs for the Treatment of Parkinson's Disease. Part I: Neurotoxins, Levodopa, and Agents Influencing Dopamine Metabolism (A Review)

Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-N-methylpyridine-2-carboxamide (AZD5305): A PARP1–DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs

“…One of our first goals was to move away from the phenyl tetrahydropyridine moiety, a substructure matching MPTP, a compound known to metabolize to MPP+ and cause irreversible Parkinson’s disease . Interestingly, the authors had reported that the tetrahydropyridine moiety could be replaced with a piperazine, albeit with approximately 4-fold lower binding potency .…”

“…One of our first goals was to move away from the phenyl tetrahydropyridine moiety, a substructure matching MPTP, a compound known to metabolize to MPP+ and cause irreversible Parkinson's disease. 32 Interestingly, the authors had reported that the tetrahydropyridine moiety could be replaced with a piperazine, albeit with approximately 4-fold lower binding potency. 23 Optimistic in the face of this, we designed two libraries with the 8-chloroquinazolinone core, one library utilizing reductive amination chemistry to attach various aryl piperazines and another library based on Buchwald−Hartwig amination to attach various aryl bromides to construct the aryl piperazine.…”