Heterocyclic RIP1 kinase inhibitors

Inventors

Shaw, Simon • Bhamidipati, Somasekhar • Taylor, Vanessa

Assignees

Rigel Pharmaceuticals Inc

Abstract

Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.

Core Innovation

The disclosure provides a method for treating a disease in a subject by administering a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, stereoisomer, N-oxide, tautomer, hydrate, solvate, isotope, or prodrug thereof, or a pharmaceutical composition containing the compound. The subject has, is suspected of having, or is developing Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, or multiple sclerosis.

The compounds are defined by Formula I and related sub-formulas, with ring B as heteroaryl and structural variables including R1 through Rf, L, X, Z, m, and n. R1 is defined as a -linker-R6 group, the linker is Ra, R6 is heterocyclyl, -C(Rf)3, or -C(Rf)-C(Rf)2, X is CH2 or O, L is a heteroatom or Ra, and Z is heteroaryl.

The disclosure also presents exemplary (S)-configured compounds, including substituted carboxamide and picolinamide variants with tetrahydrobenzo[b][1,4]oxazepin or related benzo[b]azepin cores. The examples include pyridine, pyrimidine, and related heteroaryl substituents, together with substituted ethynyl groups and other depicted substituent alternatives consistent with the Formula I scope.

Claims Coverage

The provided material centers on one independent claim for a treatment method and its structural compound definition, with dependent coverage narrowing disease selection and compound embodiments. The inventive features include the disease-treatment method, the Formula I compound framework, the R1-linked substituent constraints, and the enumerated (S)-configured example compounds.

Overall, the claims cover a treatment method for four listed diseases using structurally defined Formula I compounds, with dependent narrowing to specified disease embodiments, R1-linked substituent alternatives, and enumerated (S)-configured example compounds.

Stated Advantages

Documented Applications