Compositions of substituted pyrazolopyrimidines and uses thereof

Inventors

Liu, Hanlan • Wenslow, Jr., Robert M.

Assignees

KSQ Therapeutics Inc

Abstract

Pharmaceutical formulations comprising substituted pyrazolopyrimidines are disclosed herein. Also disclosed are amorphous solid dispersions comprising substituted pyrazolopyrimidines, processes for preparing these amorphous solid dispersions, pharmaceutical compositions comprising such dispersions, and methods of use thereof.

Core Innovation

Substituted pyrazolopyrimidine compounds, including compounds of Formula I, are described as USP1 (ubiquitin-specific-processing protease 1) inhibitors. The disclosed compounds are provided in a solid substantially amorphous form and dispersed in a polymer as an amorphous solid dispersion. The disclosure also provides pharmaceutically acceptable salts of the compounds.

The disclosed amorphous solid dispersion comprises a compound of Formula I in which R is C1-3 alkyl and X1 and X2 are independently selected from N and C. The solid substantially amorphous compound is dispersed in a polymer to form the amorphous solid dispersion. The document further includes examples where the compound is specifically selected from compounds represented by Formula II and Formula III.

Polymer-containing dispersion features are described, including polymer selection and dispersion composition constraints. Polymer components include polymers such as hydroxypropyl methylcellulose acetate succinate (HPMCAS) and EUDRAGIT, with additional named polymer classes also disclosed. The document describes reducing crystalline content and assessing amorphous versus crystalline form using characterization techniques such as XRPD and PLM, along with stability against recrystallization under humidity and temperature conditions.

Claims Coverage

The independent claims disclosed in the provided material include a primary independent claim directed to an amorphous solid dispersion defined by Formula I and dispersion in a polymer. The claims further include pharmaceutical compositions and cancer treatment methods tied to administration of the amorphous solid dispersion, along with manufacturing by spray drying a feeder solution.

The core coverage centers on an amorphous solid dispersion where a Formula I compound or pharmaceutically acceptable salt is present as a solid substantially amorphous material dispersed in a polymer, with refinements specifying Formula (II) compound selection, allowable polymer sets, polymer loading ranges, cancer treatment administration, and spray-drying manufacture from a feeder solution.

Stated Advantages

Documented Applications