Compounds useful as kinase inhibitors

Inventors

Guisot, Nicolas

Assignees

Loxo Oncology Inc

Abstract

This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.

Core Innovation

The invention relates to kinase inhibitor compounds, specifically Bruton's tyrosine kinase (BTK) inhibitors, provided as compounds of formula (I) with chiral centers indicated, and pharmaceutically acceptable salts thereof. The disclosed scaffold is defined by substituent groups A and R1-R7, with chiral centers marked by an asterisk, and additional structural definitions for the permitted variations of each substituent and attachment pattern, including the carbonyl linker C(=O).

The disclosure also describes BTK-modulating compounds based on a pyrazole carboxamide scaffold and related intermediates, including substituted pyrazole examples with varying aryl substituents and sidechains. Representative chemical examples include tetrahydrofuranyl, tetrahydropyran-3-yl, cyclopentyl, and fluorinated substituents, together with substituted phenyl, pyridyl, benzamide, and heteroaromatic carboxamide components.

The document further provides analytical characterization for multiple example compounds using UPLC-MS, LC-MS, and 1H NMR, and reports stereochemical variants and isomer handling for chiral centers. It also contemplates all enantiomers and diastereomers, specific (R)-configuration and (S)-configuration, racemic mixtures, optional additional chiral centers beyond those explicitly marked, and use in BTK-modulated conditions including cancer, lymphoma, leukemia, immunological diseases, B-cell malignancy, autoimmune and inflammatory disorders, heteroimmune conditions, and fibrosis.

Claims Coverage

The independent claims cover three core areas: a compound defined by a structural formula with chiral center marking or a pharmaceutically acceptable salt, a pharmaceutical composition containing that compound with pharmaceutically acceptable excipients, and a method of treating a BTK-modulated condition by administering the compound or its salt. Across the independent claims, the inventive features focus on the formula-defined compound scaffold, its pharmaceutically acceptable salts, formulation with excipients, and BTK-modulated therapeutic use.

Overall, the claims anchor protection around a formula-defined compound with marked chiral centers and its pharmaceutically acceptable salts, extend that coverage to pharmaceutical compositions including pharmaceutically acceptable excipients, and further extend to methods of treating BTK-modulated conditions through administration of the same compound or its salt.

Stated Advantages

Documented Applications