Substituted imidazo[1,2-B]pyridazines as protein kinase inhibitors

Inventors

Xu, Yong • Brenning, Benjamin Gary • Kultgen, Steven G. • Liu, Xiaohui • Saunders, Michael David • Ho, Koc-Kan

Assignees

Sumitomo Pharma Oncology Inc • Sumitomo Pharma America Inc

Abstract

The present invention provides a compound having the following structure: Compositions and methods for using the same in the treatment of skin disorders and other Pim kinase-associated conditions are also disclosed.

Core Innovation

The invention is directed to substituted imidazo[1,2-b]pyridazine compounds and related compound classes that function as protein kinase inhibitors, including Pim kinase inhibitors such as Pim-1, Pim-2, and Pim-3, and aurora-2 kinase activity-related compounds. The disclosed compounds are defined by structures (I), (II), (III), and related variants, with variable substituents including R, R1, R2, X, W, and additional parameters, and include stereoisomers, prodrugs, tautomers, E/Z isomers, and pharmaceutically acceptable salts.

The compound definitions include broad substituent scope and multiple structural families, including imidazo[1,2-b]pyridazine, pyrazolo[1,5-a]pyrimidine, and related polycyclic fused aza-heteroaromatic scaffold variants. The definitions also include phenyl-substituted, fluorinated, and heterocycle-containing motifs such as piperidyl, piperazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholino, cyclohexanol, and thiopyran dioxide derivatives, together with linker and oxidation variants involving O, S, S(O), and S(O)2.

The disclosure further includes general preparation frameworks and representative synthetic examples for the disclosed structures, with characterization by NMR and ESI-MS. It also describes pharmaceutically acceptable compositions containing one or more of the compounds, optionally together with one or more additional therapeutic agents, and mentions downstream formulation and administration concepts in connection with Pim kinase-related cancers, inflammatory disorders, autoimmune conditions, and skin disorders.

Claims Coverage

The independent claims are directed to a pharmaceutical composition, a method for inhibiting proviral insertion in murine kinase activity, and a method for treating a skin disorder. Across the independent claims, the core inventive features center on administering or formulating a compound having a specified structure, or a pharmaceutically acceptable salt thereof, and in the composition and some method embodiments, combining it with one or more additional therapeutic agents.

The claims collectively cover compositions and methods using a structurally defined compound, or a pharmaceutically acceptable salt thereof, with optional inclusion of one or more additional therapeutic agents. The therapeutic scope specifically includes inhibiting proviral insertion in murine kinase activity and treating skin disorders.

Stated Advantages

Documented Applications