pyrazolopyridine and Neurodegenerative-Diseases

Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP

Topics: Apoptosis Regulatory Proteins; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Heterocyclic Compounds; Humans; Neuroblastoma; Neurodegenerative Diseases; Neuroprotective Agents; Pyrazoles; Pyridines

Direct functionalization and tandem processes have both received considerable recent interest due to their cost and time efficiency. Herein we report the synthesis of difficult to obtain 2-substituted pyrazolo[1,5-a]pyridines through a tandem palladium-catalyzed/silver-mediated elimination/direct functionalization/cyclization reaction involving N-benzoyliminopyridinium ylides. As such, these biologically important molecules are prepared in an efficient, high-yielding manner, only requiring a two-step sequence from pyridine. Aryl-substituted alkenyl bromides and iodides are effective ylide coupling partners. Mechanistic studies led to the use of terminal alkynes, which extended the scope of the reaction to include alkyl substitution on the unsaturated reactive site. The optimization, scope, and mechanistic considerations of the process are discussed.

Topics: Alkenes; Alkynes; Bromides; Catalysis; Chemistry, Pharmaceutical; Cyclization; Dopamine Agonists; Dopamine Antagonists; Humans; Iodides; Magnetic Resonance Spectroscopy; Neurodegenerative Diseases; Palladium; Pyrazoles; Pyridines; Receptors, Dopamine; Silver