Pharmaceutical compositions comprising phenylsulfonamides, and their therapeutic applications
Inventors
Assignees
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Publication Number
US-11701334-B2
Publication Date
2023-07-18
Expiration Date
Abstract
Provided herein are pharmaceutical compositions, each comprising a phenylsulfonamide, for example, a compound of Formula I, or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; and a pharmaceutically acceptable excipient. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a neurodegenerative disease.
Core Innovation
The invention relates to a method of treating one or more symptoms of Alzheimer's disease in a subject by administering a pharmaceutical composition comprising a compound of Formula I together with a pharmaceutically acceptable excipient. The compound may be administered as an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, an isotopic variant, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
Formula I is defined by substituent variables in which X is either —SO2— and Y is —NRX— or X is —NRX— and Y is —SO2—. The invention further specifies structural substitution constraints for R1, R2, R3, R4, R5, R6, RX, and an integer m, including optional substitution of alkyl and alkoxy substituents by Q, and it includes stereochemical, tautomeric, and isotopic variants as part of the defined compound scope.
The disclosed treatment concepts include inhibiting amyloid β production and attenuating amyloid β level and amyloid β-induced signaling pathway activity. The biological effect is also described in terms of inhibiting tau protein production and attenuating tau level and tau activity, including phosphorylated tau and hyperphosphorylated tau species.
Claims Coverage
The partial content provides one independent claim. It covers a treatment method in which administration is directed to Alzheimer's disease symptoms using a Formula I compound, including stereochemical, tautomeric, isotopic, salt, solvate, and hydrate forms, formulated with a pharmaceutically acceptable excipient; the claim then constrains the method by specific Formula I structural relationships and detailed substituent definitions.
Alzheimer’s disease symptom treatment by administering Formula I composition
Administering to a subject a pharmaceutical composition comprising a compound of Formula I, or an enantiomer, mixture of enantiomers, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or an isotopic variant; or a pharmaceutically acceptable salt, solvate, or hydrate thereof, and a pharmaceutically acceptable excipient, for treating one or more symptoms of Alzheimer's disease.
X/Y sulfonamide-sulfoxide arrangement and m constraint in Formula I
Wherein X is —SO2— and Y is —NRX— or X is —NRX— and Y is —SO2—; RX is hydrogen; and m is an integer of 0, 1, or 2.
Substituent definition for R1–R6 and allowed Q substitution patterns
Each R1 is independently halo or C1-6 alkyl; R2 and R4 are each hydrogen; R3 is nitro, C1-6 alkyl, C1-6 alkoxy, or C1-6 alkylsulfonamido; R5 is hydrogen or C1-6 alkoxy; R6 is hydrogen, C1-6 alkyl, or C1-6 alkoxy; and each alkyl and alkoxy is optionally substituted with one, two, three, or four substituents Q selected from the enumerated groups.
The independent claim defines a specific therapeutic method for Alzheimer's disease symptoms based on administration of a Formula I compound, including stereochemical, tautomeric, isotopic, and salt, solvate, and hydrate forms, in a pharmaceutical composition with an excipient. It further requires a defined structural arrangement for X and Y, a hydrogen constraint for RX, an m value in {0,1,2}, and limitations on substituents R1–R6 and optional Q substitution patterns.
Stated Advantages
Inhibits amyloid β production and attenuates amyloid β level and amyloid β-induced signaling pathway activity.
Inhibits tau protein production and attenuates tau level and tau activity, including phosphorylated tau and hyperphosphorylated tau.
Documented Applications
Treating one or more symptoms of Alzheimer's disease in a subject by administering a pharmaceutical composition containing a Formula I phenylsulfonamide compound.
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