CGAS antagonist compounds

Inventors

Zhong, Boyu • Sun, Lijun • Shi, Heping • Li, Jing • Chen, Chuo • Chen, Zhijian

Assignees

University of Texas System • Immunesensor Therapeutics Inc

Abstract

Disclosed are novel compounds of Formula I that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.

Core Innovation

The invention relates to a method for treating a disease or condition responsive to antagonism of cyclic GMP-AMP synthase (cGAS) activity by administering to a patient in need thereof a therapeutically effective amount of a compound of Formula Ia or a pharmaceutically acceptable salt thereof. The treated disease or condition includes systemic lupus erythematosus, psoriasis, insulin-dependent diabetes mellitus (IDDM), scleroderma, Aicardi Gourtiers syndrome, dermatomyositis, inflammatory bowel diseases, multiple sclerosis, rheumatoid arthritis, Sjogren's syndrome (SS), Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, atherosclerosis, myocardial infarction, cardiovascular disease, senescence, or ocular inflammation.

Formula Ia is characterized by structural variables including X as NH or S, Y as O or S, and Z as O, S, CHR1a, or NR1a, with G as N or C and defined connectivity relationships between R1 and R1a. The compound definitions provide allowed values for R1, R2, R2a, and additional substituent variables, including hydrogen, C1-6 alkyl, halogen, and C1-6 alkyl selectively functionalized with one or more listed groups such as thiol, hydroxyl, carbonyl, carboxyl, carbonyloxyl, C1-6 alkoxy, C1-6 hydroxyalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, or azido groups.

The structural scope further includes phenyl or heteroaryl groups selected from imidazolyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl, with optional substitution patterns and additional optional substituent groups for R3a, R3b, R4a, R5a, R6a, R7a, R8a, and R9a. The provided content also shows example compound structures and MS-related example entries for Formula Ia variants, supporting the claimed chemical space for cGAS-antagonism treatment compounds.

Claims Coverage

The consolidated claim coverage centers on one independent treatment method claim directed to cGAS antagonism-responsive diseases or conditions. The method requires administration of a therapeutically effective amount of a compound of Formula Ia or a pharmaceutically acceptable salt thereof, with the principal inventive features being the therapeutic method, the defined disease scope, and the detailed Formula Ia structural framework.

The claim coverage is consolidated around administering a therapeutically effective amount of a Formula Ia compound, or a pharmaceutically acceptable salt, to treat diseases or conditions responsive to cGAS antagonism. The structural inventive scope is defined by the Formula Ia variable selections and connectivity rules, together with the enumerated disease list and optional heteroaryl substitution patterns.

Stated Advantages

Documented Applications