Proteolysis of alpha synuclein protein targeting a chimeric (protac) compound with E3 ubiquitin ligase binding activity to treat neurodegenerative diseases

摘要

This disclosure relates to a bifunctional compound that finds utility as an regulator of alpha synuclein (target protein).EspeciallyThe present disclosure includesA bifunctional compoundAt one endVon Hippel Lindow, which binds to each E3 ubiquitin ligaseCelledonInhibitor of apoptosis proteinOr a mouse double microhomologue 2 ligandOn the other endContains a part that binds to the target proteinAs a resultTarget proteinLocated close to the ubiquitin ligaseCausing the degradation and inhibition of target proteinsBifunctional compounds.The present disclosure shows a wide range of pharmacological activity associated with the degradation / inhibition of target proteins.Diseases or disorders resulting from targeted protein aggregation or accumulation are treated or prevented using compounds and compositions of the present disclosure.Such diseases or disorders include, for example, Parkinson's disease, Alzheimer's disease, dementia, Lewy body type dementia, or multiple system atrophy, especially Parkinson's disease Alpha cyncryanopathy or neurodegenerative disease associated with alpha synuclein accumulation and aggregation.