Oxazolidine-based compound and selective androgen receptor agonist comprising same

Inventors

Choi, Sung Pil • Choi, Seul Min • Son, Byoung Hwa • Kim, Hyun Jung • Kim, Ju Mi • Jang, Byung Jun • SUNG, Ji Hyun • Lee, Ji Hye • Kim, Eunjin • Kang, Kyung Koo • Kim, Soon-Hoe

Assignees

Dong-A ST Co Ltd

Abstract

Provided are novel selective androgen receptor agonists, a preparation method thereof, and a pharmaceutical composition including the same at a pharmaceutically effective amount. The selective androgen receptor agonists according to the present invention act on androgen receptors to increase androgen activity, thereby being usefully applied as a therapeutic and prophylactic agent for diseases or conditions, of which symptoms may be improved or may respond to treatment by increased activities of androgen receptors, namely, a variety of hormone-related diseases in male and female, muscle wasting disorders, osteoporosis, etc.

Core Innovation

The disclosure describes compounds represented by Chemical Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, defined by substituent variables R1 to R7 and a substituted framework involving X(CH2)nR8 and R8 defined by Chemical Formula 2, or by Chemical Formula 3 with Y and m parameters. R1 is represented by Chemical Formula 2 or Chemical Formula 3, and the substituent options explicitly include hydrogen, oxo, halogen, cyano, nitro, alkyl groups, and multiple functional groups and heterocycle/aryl substituents.

Chemical Formula 2 specifies X as O, N(R), S, or S(O)2, with R8 as hydrogen, C3-C7 heterocycle having a nitrogen atom, aryl, or heteroaryl having a nitrogen atom and one or two rings, and with substitution patterns including hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, cyano, nitro, hydroxyimino, C1-C6 alkoxyimino, and multiple carbonyl-related groups and sulfonyl groups. Chemical Formula 3 specifies Y as C or N, m as an integer of 0, 1, or 2, and R9 as hydrogen, oxo, hydroxy, C1-C6 alkyl, cyano, and various carbonyl, sulfonyl, and amide/amine-related substituents.

The disclosure further describes selective androgen receptor agonists (SARMs) that increase androgen receptor activity, with compounds based on an oxazolidine framework and stereochemical and mixture formats including racemic mixtures, enantiomers, and diastereomers. Reaction schemes are also described for preparation of related compounds from fluorobenzene intermediates through substitution, cyclodehydration, oxidation, silane reaction followed by acid treatment, and amide formation.

Claims Coverage

The independent claims provided include a compound/formula claim, a pharmaceutical composition claim, and method claims for preparing Chemical Formula 1a and Chemical Formula 1d, for a total of 4 independent claim types across the inputs. The claim coverage centers on the constrained Chemical Formula 1 scaffold with detailed substituent definitions and on multi-step preparation sequences starting from a fluorobenzene compound of Chemical Formula 4.

Across the independent claims, the inventive subject matter is centered on a constrained Chemical Formula 1 compound family, a pharmaceutical composition using the claimed compound for diseases or conditions responsive to increased androgen receptor activity, and two preparation methods that convert a fluorobenzene compound through substitution and cyclodehydration, with one route further including amide formation to reach Chemical Formula 1d.

Stated Advantages

Documented Applications