Pyrazolyl and pyrimidinyl tricyclic enones as antioxidant inflammation modulators

Inventors

Anderson, Eric • Bolton, Gary L. • Caprathe, Bradley • Jiang, Xin • Lee, Chitase • Roark, William H. • Visnick, Melean

Assignees

AAPHARMASYN LLC • Reata Pharmaceuticals Inc

Abstract

Disclosed herein are novel antioxidant inflammation modulators, including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds. Methods and intermediates useful for making the compounds, and methods of using the compounds and compositions thereof are also provided.

Core Innovation

The disclosure provides a family of compounds defined by specific chemical formulas, including fused-ring bicyclic and pyrazolyl and pyrimidinyl tricyclic enone scaffolds. The compounds are characterized by variable parameters such as n and substituent positions R1 through R8, with explicit scope limits for hydrogen, alkyl, aryl, aralkyl, heteroaryl, halo, cyano, amino, oxo, acyl, alkoxy, and amido groups, as well as salts and tautomers.

The described subject matter also includes compounds having nitrile and carbonyl or oxo groups within the fused-ring framework, with R1 and R2 optionally taken together as an alkanediyl group. R3, R5, and R6 are further restricted to defined presence or absence and substituent classes, and some embodiments specify stereochemical descriptors, optical isomers, enantiomers, and pharmaceutical compositions with an excipient.

The document further presents numerous example compounds and substituted derivatives, including compounds identified by number and series designations, together with structural variants bearing halo, alkoxy, alkyl, fused aromatic, carboxamide, ester, carboxylate, and ether or oxo motifs.

Claims Coverage

The consolidated claim coverage centers on formula-defined compound families with variable scaffold parameters and restricted substituent classes. Across the independent claims reflected in the inputs, there are 6 inventive feature groups: the core chemical formula or scaffold, the n parameter, the R1 and R2 substitution pattern, the R3 and R5 substitution pattern, the broadened R6 functional-group scope, and salt or tautomer inclusion.

Overall, the claims define compound families by formula, scaffold parameter n, and constrained substituent options at R1, R2, R3, R5, and R6, including optional salts or tautomers. Dependent claims narrow these features by fixing n, specifying particular R1 and R2 identities or tethering, and enumerating selected R5 and R6 substituent sets.

Stated Advantages

Documented Applications