Quaternary indazole glucocorticoid receptor antagonists

Inventors

Hunt, Hazel • Duffy, Lorna • STRUTT, Ian • JOUANNEAU, Morgan • HORNSBY, Thomas • Mills, Mark • Phillips, Andrew William • WARD, Jon-Paul

Assignees

Sygnature Discovery Ltd • Corcept Therapeutics Inc

Abstract

The present disclosure provides compounds of Formula I or II. Compounds of Formula I or II may be used in pharmaceutical formulations, and may be used for modulating glucocorticoid receptors.

Core Innovation

The invention relates to methods of treating a disorder or condition by modulating or antagonizing a glucocorticoid receptor through administering a therapeutically effective amount or an effective amount of a compound of Formula IVa, or a pharmaceutically acceptable salt thereof, to a subject in need of such treatment. The compounds are defined by extensive structural variables including R1, R1a, A1-A4, R2, R3a, R3b, R3b3, R4, R4a, R4b, R4c, and the link/atom variables L1 and L2, with explicit absence of L1 and L2 in the stated embodiments.

R1 is defined as heterocycloalkyl, phenyl, or heteroaryl with specified ring-member and heteroatom counts, substituted with 1 to 3 R1a groups. R1a, R2, R3a, R3b, and R4 are each selected from enumerated chemical group classes, and aryl or heteroaryl portions are further limited by defined substitution ranges. The disclosure also includes specific example embodiments, including indazole-based and sulfonyl-linked scaffolds with heterocycle and aryl substitution patterns.

The document further describes exemplified compounds and intermediates associated with Formula IVa chemical space, including sulfonylated indazole-pyrrolidine-pyridine scaffolds, triazole- and pyrazole-containing motifs, and stereochemical variants. It also states that the compounds are used in methods for treating disorders or conditions by glucocorticoid receptor modulation or antagonism, and includes enumerated tables of structures and analytical characterization for example compounds and intermediates.

Claims Coverage

Two independent claims are provided. Both are directed to methods of treating a disorder or condition by administering a therapeutically effective or effective amount of a compound of Formula IVa, or a pharmaceutically acceptable salt thereof, with one claim directed to glucocorticoid receptor modulation and the other to glucocorticoid receptor antagonism. The claims collectively define the scope through detailed structural constraints on R1, R1a, A1-A4, R2, R3a, R3b, R3b3, R4, R4a, R4b, R4c, and L1/L2.

Across the independent claims, the inventive coverage centers on therapeutic administration of Formula IVa compounds, or pharmaceutically acceptable salts, to treat disorders or conditions by glucocorticoid receptor modulation or antagonism. The scope is defined by the same detailed Formula IVa structural framework, including constrained substituent classes, ring-member and heteroatom limits, substitution limits, and explicit absence or restriction of L1 and L2.

Stated Advantages

Documented Applications