Selective androgen receptor modulators

Inventors

Miller, Chris P.

Assignees

Ellipses Pharma Ltd

Abstract

This invention provides compounds as described herein or pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound as described herein or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor using the compounds or compositions described herein, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) using the compounds and compositions described herein and processes for making compounds described herein and intermediates useful in the preparation of same.

Core Innovation

The disclosure describes specific (R)-configured oxadiazole-containing benzonitrile compounds including pharmaceutically acceptable salts, with defined ring substituents and side chains such as hydroxy-2-methylpropylamino, 2-hydroxypropylamino, and 3,3,3-trifluoro-2-hydroxypropylamino. The compounds include a 1,3,4-oxadiazol group and substituted benzonitrile cores with aryl groups such as 4-fluorophenyl and 4-cyanophenyl, and the patent presents specific compound members as chemical structures and salts.

The patent also describes pharmaceutical compositions that include the compounds and pharmaceutically acceptable excipients, together with formulation and administration options. The disclosed compositions are intended for modulating androgen receptor activity in androgen-receptor-expressing cells and for treating conditions associated with androgen signaling or insufficiency, and the document includes stereoisomer, salt, and solvate characterizations.

The disclosure further describes methods that modulate androgen receptor activity by contacting androgen-receptor-expressing cells with a compound and methods that identify compounds capable of androgen receptor modulation by contacting androgen-receptor-expressing cells and monitoring the effect. The patent includes androgen receptor binding assay description using IC50 determination and in vivo Herschberger-style rat assay comparison, and reports that Example 7 increases levator ani muscle in castrated rats.

The therapeutic use is directed to conditions associated with androgen signaling or insufficiency, including sarcopenia and wasting syndromes such as AIDS-related cachexia and cancer cachexia. Additional disease areas are stated to include prostate cancer and other diseases spanning metabolic, renal, and neuropsychiatric disorders, and the background frames the compounds as tools for androgen receptor-related outcomes.

Claims Coverage

The independent claims present three main claim categories: specific (R)-configured oxadiazole-containing benzonitrile compounds, pharmaceutical compositions of the claimed compounds with pharmaceutically acceptable excipients, and methods of using the compounds for androgen receptor modulation, compound identification, and treatment or amelioration of specified androgen-associated conditions. Across the independent claims, the coverage centers on two enumerated compound claims and method claims directed to androgen receptor modulation, identification, and therapeutic use.

The claim coverage centers on narrowly enumerated (R)-configured oxadiazole-containing benzonitrile structures, optionally as salts, with downstream claims directed to pharmaceutical compositions, androgen receptor modulation through contacting androgen-receptor-expressing cells, compound identification based on monitoring cellular effects, and therapeutic methods for ameliorating sarcopenia and wasting or cachexia symptoms.

Stated Advantages

Documented Applications