Benzofuran, benzothiophene, and indole analogs that inhibit the formation of tau oligomers and their method of use

Inventors

Davidowitz, Eliot J. • Moe, James G. • Reitz, Allen B. • Bian, Haiyan • Gluchowski, Charles • Hendrix, James • Yehaskel, Albert S. • McDonnell, Mark E. • Loughran, H. Marie

Assignees

Oligomerix Inc

Abstract

Novel benzofurans, benzothiophenes and indoles useful as inhibitors of tau oligomer formation, useful for the treatment of neurodegenerative diseases and related conditions are disclosed. The invention also relates to the pharmaceutically acceptable salts of said compounds, processes for the preparation of said compounds, intermediates used in the preparation of said compounds, and pharmaceutical compositions containing said compounds. The invention further relates to methods of use of said compounds, salts of said compounds, and said compositions in treating neurodegenerative diseases and related conditions.

Core Innovation

The patent provides a compound selected from compounds of formula (I) and numerous related formulas (II) through (XVIII), where the compounds include enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, and complexes thereof. The structural scope is defined using variable-group selections such as R1a and R1d independently selected from hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; R1b and R1c selected from hydrogen, halogen, optionally substituted aryl, and optionally substituted heteroaryl, with mutual non-hydrogen conditions.

Additional substituent constraints define R2, X, R5, Y, R6, and further grouped substituent relationships that specify ring formation and allowed group selections. The specification further includes compounds having formulas (XIV) through (XVIII), with defined variable-group frameworks using sets of allowed A1–A10 that are selected from nitrogen and CR10, including limits on how many of those substituent positions may be nitrogen.

Across these formula variants, R9a, R9b, and R9c are defined, X1 is oxygen or sulfur in the later formula set, and R10 and R11 are constrained to selections including hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy, halogen, hydroxy, and NHSO2R11, while R11 is independently hydrogen and C1-6 alkyl. The patent also references examples provided in Tables 1-3 and specific compound embodiments consistent with the described R-group-defined scaffold.

Claims Coverage

The document contains one independent claim that covers a compound selected from multiple structural formula families with extensive substituent definitions. The independent claim includes formula (I) and named variants through formula (XVIIIb), and expressly includes stereoisomeric and formulation-derivative forms.

The independent claim broadly covers a compound selected from multiple named structural formulas with detailed substituent definitions, conditional hydrogen selection rules, and ring-forming constraints. It also expressly encompasses enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, and complexes.

Stated Advantages

Documented Applications