Compounds for treating huntington's disease
Inventors
Sydorenko, Nadiya • Babu, Suresh • Bhattacharyya, Anuradha • Moon, Young-Choon • Narasimhan, Jana • Patel, Jigar S.
Assignees
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Publication Number
US-12103926-B2
Publication Date
2024-10-01
Expiration Date
Abstract
The present description relates to compounds, forms, and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.In particular, the present description relates to substituted monocyclic heteroaryl compounds of Formula (I), forms and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.
Core Innovation
The invention is directed to a compound, or a form thereof, selected from substituted pyrazine/pyrazole scaffold molecules and substituted monocyclic heteroaryl compounds of Formula (I). The scaffold includes a pyrazin-2-yl core substituted by a methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino group and further substituted with pyridinyl, imidazolyl, pyrazolyl, and other heteroaryl groups on a phenyl ring, together with phenol/oxylated variants and related analogs.
The disclosure recites variable groups including a linker (X), substituents (R1a, R1b, B, R2, R3, R4), and an integer n (1-3), and covers salts, hydrates, solvates, racemates, stereoisomers, enantiomers, diastereomers, tautomers, and other selected forms. It also describes pharmaceutical compositions comprising the compounds, or forms thereof, with pharmaceutically acceptable excipients.
The document further states methods and uses for treating, preventing, or ameliorating Huntington’s disease, including decreasing mutant HTT by contacting human cells with the compounds such that mutant HTT transcription from the Htt gene is inhibited or mutant HTT expression is inhibited. Representative members and intermediates are characterized, and in vitro endogenous huntingtin protein assessment is described using an ELISA/MSD assay with potency presented by IC50 values.
Claims Coverage
The claims cover substituted pyrazine/pyrazole-containing compounds and specified Formula (I) compounds, together with selected compound forms and pharmaceutical compositions. Four inventive features are identified across the claims.
Substituted pyrazine/pyrazole compound group with enumerated scaffold members
A compound, or a form thereof, selected from the enumerated substituted pyrazine/pyrazole-containing structures and selected Formula (I) compounds, including pyrazin-2-yl substitution and pyridinyl, imidazolyl, pyrazolyl, or other heteroaryl substitutions, together with phenol/amine or oxy-functionalized variants and related analogs.
Compound form selection as salts, hydrates, solvates, stereochemical and tautomer forms
The compound is defined such that a form of the compound is selected from the group consisting of a salt, hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof.
Pharmaceutical composition with pharmaceutically acceptable excipients
A pharmaceutical composition including the compound, or its form, together with one or more pharmaceutically acceptable excipients.
Pharmaceutical composition with pharmaceutically acceptable excipients for salt forms
A pharmaceutical composition including the compound salt, or a form thereof, together with one or more pharmaceutically acceptable excipients.
Overall claim coverage includes substituted pyrazine/pyrazole scaffold compounds and Formula (I) compounds, permitted compound forms including salts and other listed forms, and pharmaceutical compositions containing those compounds or their salt forms.
Stated Advantages
Treating, preventing, or ameliorating Huntington’s disease (HD).
Decreases mutant HTT by inhibiting mutant HTT transcription from the Htt gene or inhibiting mutant HTT expression in human cells.
Therapeutic effects for HD are described in terms of reduced severity, delayed onset, reduced progression, and improved survival/quality of life.
Use in combination therapy with other therapeutic agents.
Documented Applications
In vitro endogenous huntingtin ELISA/MSD assay evaluation of compounds, with potency indicated by IC50 values for Huntington’s disease treatment relevance.
Prevention, treatment, or amelioration of Huntington’s disease (HD) using compounds of Formula (I) and their salt forms.
Therapeutic methods for Huntington’s disease (HD) using Formula (I) compounds by contacting human cells to inhibit mutant HTT transcription or mutant HTT expression.
Pharmaceutical use for Huntington’s disease (HD) via pharmaceutical compositions comprising Formula (I) compounds, or forms, with pharmaceutically acceptable excipients.
Combination therapy for HD using Formula (I) compounds with other therapeutic agents.
Approaches involving modulation of mutant HTT and/or HTT protein expression.
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