Prodrugs of STAT3 inhibitors

Inventors

Alibhai, Imran • De Achaval, Sofia • Larson, Jeffrey • Henke, Brad

Assignees

Tvardi Operating Company Inc

Abstract

Provided herein, in certain embodiments, are compounds of Formula I. or a pharmaceutically acceptable salt or a solvate thereof, compositions comprising a compounds of Formula I, or a pharmaceutically acceptable salt or a solvate thereof, and uses thereof such as in treating certain diseases or disorders (e.g., cancer, fibrosis, chronic inflammation).

Core Innovation

The invention relates to STAT3 inhibitor prodrugs as compounds represented by Formula I, including pharmaceutically acceptable salts and solvates. The disclosed compounds are defined broadly through substituent scope using parameters such as A, R1, R2, R3, and n, and through multiple Formula I variants, including forms described as ester, carbonate, and phosphonate-like variants. This structural framework is presented as the basis for creating STAT3 inhibitor prodrugs within Formula I.

The disclosed subject matter includes corresponding pharmaceutical compositions comprising the Formula I compounds or pharmaceutically acceptable salts. The document further describes that the compounds are intended for treating or preventing cancer, fibrosis, and inflammatory diseases or disorders. The structural disclosure includes examples of specific Formula I sub-structures, which supports the stated range of STAT3 inhibitor prodrug forms.

The background comparison describes that a prior STAT3 inhibitor, TTI-101, is poorly soluble and forms high-lattice-energy crystals, while the Formula I compounds are asserted to have improved aqueous solubility and chemical stability across multiple pH values. The document also states that these improvements are maintained while maintaining comparable pharmacokinetic properties relative to the prior inhibitor.

Claims Coverage

The independent claims explicitly cover a compound represented by Formula I, a pharmaceutical composition comprising that compound, and method claims that inhibit STAT3 by administering an effective amount. In total, five inventive features are identified across the claim set.

Overall, the claims coverage focuses on Formula I STAT3 inhibitor prodrugs and pharmaceutically acceptable salts, pharmaceutical compositions using a pharmaceutically acceptable carrier, and therapeutic methods that inhibit STAT3 for cancer, fibrosis, and inflammatory diseases or disorders by administering an effective amount of the Formula I compounds or their salts.

Stated Advantages

Documented Applications