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Novel Gamma-Secretase Modulators for the Treatment of Alzheimer's Disease and Related Neurodegenerative Disorders

詳細技術說明

Researchers at UC San Diego have developed methods for synthesizing and testing a number of novel gamma-secretase modulators with dramatically improved aqueous solubilities. The enhanced aqueous solubilities of these gamma-secretase modulators are expected to exhibit improved pharmacokinetic and pharmacodynamic properties compared to the 2-aminothiazole GSM compounds previously described in U.S. patent 7,244,739. The present invention is a new class of soluble GSMs that promises to be far more amenable to preclinical and clinical development protocols as a result of their enhanced aqueous solubilities. SGSM technology covered by this invention may prove useful for treating diseases associated with altered levels of certain Aβ peptide alloforms (i.e., Aβ42 and Aβ40), such as Alzheimer’s disease, Down’s syndrome, hereditary cerebral hemorrhage with amyloidosis-Dutch Type, cerebral amyloid angiopathy, and mild cognitive impairment, as well as a number of other neurodegenerative proteinopathies (e.g. Creutzfeldt-Jakob disease, frontotemporal dementias, amyotropic lateral sclerosis, Huntington’s disease, Parkinson’s disease).

附加資料

Inventor: WAGNER, Steven, L. | CHENG, Soan | MOBLEY, William, C. | TANZI, Rudolph, E.
Priority Number: WO2011163636A3
IPC Current: C07D041714 | A61K00314427 | A61K00314439 | A61P002500 | C07D040104
Assignee Applicant: The Regents of the University of California
Title: COMPOUNDS AND USES THEREOF IN MODULATING LEVELS OF VARIOUS AMYLOID BETA PEPTIDE ALLOFORMS | COMPOSÉS ET LEURS UTILISATIONS DANS LA MODULATION DES NIVEAUX DE DIFFÉRENTES ALLOFORMES DU PEPTIDE AMYLOÏDE BÊTA
Usefulness: COMPOUNDS AND USES THEREOF IN MODULATING LEVELS OF VARIOUS AMYLOID BETA PEPTIDE ALLOFORMS | COMPOSÉS ET LEURS UTILISATIONS DANS LA MODULATION DES NIVEAUX DE DIFFÉRENTES ALLOFORMES DU PEPTIDE AMYLOÏDE BÊTA
Summary: For treating a disease or neurological disorder associated with elevated levels of specific fibrillogenic (Aβ ) peptides, the disease is selected from Alzheimer's disease, hemorrhagic stroke associated with cerebrovascular amyloidosis (HCHWA), or cerebral amyloid angiopathy (CAA), idiopathic dilated cardiomyopathy, Down Syndrome (DS), Parkinson's disease (PD), Lewy body dementia (LBD), Prion diseases, inclusion body myositis (IBM), or Huntington's disease (HD) (all claimed), also for treating mild cognitive impairment, or amyotrophic lateral sclerosis.
Novelty: New tetra-(hetero)aryl compounds useful for treatment of e.g. Alzheimer's disease, hemorrhagic stroke associated with cerebrovascular amyloidosis, or Parkinson's disease