Compositions and methods for treating and preventing neurodegenerative disorders
Inventors
Kocis, Petr • TOLAR, Martin • Hey, John
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12187668-B2
Publication Date
2025-01-07
Expiration Date
Abstract
Compounds, pharmaceutical compositions, methods and kits are described for treating or preventing neurodegenerative diseases such as Alzheimer's disease.
Core Innovation
The invention relates to compounds having a structural formula (IV-1), or pharmaceutically acceptable salts thereof. The structural definition includes variable substituents R1, R7 and R8, and substituent frameworks that include hydrogen, carboxylic acid and carboxylate forms, carbonyl-linked side-group patterns, and natural or unnatural amino-acid side groups through defined RA and RB selections.
Each R7 and each R8 is independently selected from hydrogen, amino-related groups, carboxyl or carboxylate-containing groups, sulfonic acid or sulfonate-containing groups, deuterium, halogen, alkyl, alkoxy, alkenyl, alkynyl, cyano, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. Each RA is independently selected from hydrogen or a side group of a natural or unnatural amino acid, while RB is selected from hydrogen and a protecting group, including Cbz in narrower embodiments.
The structure also includes options in which each Ra is hydrogen or optionally substituted alkyl, and each Rb is selected from hydrogen, alkyl substituted with a carboxyl or a carboxylate, and an amino acid or a dipeptide bound to the nitrogen atom in R3 through a carboxy group; alternatively, Ra and Rb are taken together to form an optionally substituted heterocyclyl. The disclosure includes amino-acid-derived intermediates and final compounds bearing protecting groups, together with structural and analytical characterization.
Claims Coverage
The claims center on one independent compound claim for structural formula (IV-1) or pharmaceutically acceptable salts, with broad substituent definitions spanning R1, R7, R8, RA, RB, Ra, and Rb. Dependent claims narrow substituent choices, and method-of-use claims add treatment of Alzheimer's disease, including ApoE4-positive and homozygous ApoE4 patient subgroups.
Structural formula (IV-1) compound and pharmaceutically acceptable salts
A compound having structural formula (IV-1) or a pharmaceutically acceptable salt thereof, with R1 selected from hydrogen, carboxylic acid and carboxylate forms, and carbonyl-linked amino-acid or dipeptide patterns.
Enumerated substituent options for R7 and R8
Each R7 and each R8 is independently selected from hydrogen, amino and amide-linked groups, hydroxyl, carboxylic acid/carboxylate, sulfonic acid/sulfonate, deuterium, halogen, alkyl, alkoxy, alkenyl, alkynyl, cyano, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl.
Amino-acid and dipeptide framework for Ra and Rb
Each Ra is hydrogen or optionally substituted alkyl; each Rb is selected from hydrogen, alkyl substituted with a carboxyl or a carboxylate, and an amino acid or a dipeptide bound to the nitrogen atom in R3 through a carboxy group; or Ra and Rb are taken together to form an optionally substituted heterocyclyl.
Amino-acid side group selection for RA and protecting-group option for RB
Each RA is independently selected from hydrogen or a side group of a natural or unnatural amino acid, and RB is selected from hydrogen and a protecting group.
Alzheimer's disease treatment by administration of the IV-1 compound
A method of treating Alzheimer's disease by administering to a patient a compound described by the structural formula (IV-1).
ApoE4-positive patient treatment
The Alzheimer's disease treatment method is carried out in a patient who is ApoE4-positive.
ApoE4 homozygous patient treatment
The Alzheimer's disease treatment method is applied to a patient who is homozygous for ApoE4.
Overall, the claim coverage is directed to a structurally defined compound class of formula (IV-1) with broad but enumerated substituent options, including amino-acid/dipeptide-derived nitrogen substituents and protecting-group selection for RB. Dependent claims further narrow substituent choices and define treatment of Alzheimer's disease, including ApoE4-positive and homozygous ApoE4 patient stratification.
Stated Advantages
Reduces amyloid aggregation by inhibiting toxic oligomers, fibrils, and plaque formation.
May promote clearance.
Enables treatment and prevention of Alzheimer's disease.
Documented Applications
Treatment of Alzheimer's disease by administering a compound having the structural formula (IV-1) or a pharmaceutically acceptable salt thereof.
Patient stratified treatment of Alzheimer's disease in ApoE4-positive patients.
Patient stratified treatment of Alzheimer's disease in ApoE4 homozygous patients.
Interested in licensing this patent?