Quinoline and quinazoline compounds and methods of use thereof

Inventors

Vankayalapati, Hariprasad • Sharma, Sunil • Kaadige, Mohan Rao • Weston, Alexis

Assignees

Stingray Therapeutics Inc

Abstract

Compounds and methods for their preparation and use as therapeutic or prophylactic agents, for example for treatment of cancer, bacterial or viral diseases by targeting Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 (ENPP1).

Core Innovation

The disclosure relates to ENPP1 inhibitor compounds, including substituted quinoline and quinazoline compounds, small-molecule intermediates, scaffolds, and analogs, and related pharmaceutically acceptable salts and pharmaceutical compositions. The compounds are defined by structural variables including L, X, A, Y, and R1-R3, and include piperidine derivatives, piperazine derivatives, cyclopropyl-substituted intermediates, substituted quinazolinols, methoxymethoxy derivatives, and related scaffold features.

The subject matter further includes sulfamoylcarbamate, sulfonamide, sulfuricdiamide, phosphate prodrugs, esters, amides, N-oxides, solvates, hydrates, tautomers, polymorphs, and isotopically labelled compounds. The disclosure also describes synthetic conversions among Boc-protected intermediates, amine hydrochlorides, sulfamoylcarbamates, sulfonamides, and sulfuricdiamide formate salts, together with salts and derivative forms.

The problem addressed is ENPP1 activity and its relationship to therapeutic intervention, including cancer, disorders of uncontrolled cellular proliferation, ENPP1-associated neurodegenerative disorders, and ENPP1 dysfunction-related conditions. The therapeutic scope described in the partial content includes cancers with ENPP1 overexpression and additional indications including cardiovascular, diabetes/obesity, antiviral, antibacterial, and anti-fibrotic disorders, as well as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease.

Claims Coverage

The provided claim coverage centers on pharmaceutically acceptable salts of the claimed compound, with dependent claims adding a pharmaceutical composition and a cancer-treatment method in a mammal characterized by ENPP1 overexpression. Three inventive features are consistently recited across the items.

Across the independent and dependent claims provided, the coverage is directed to pharmaceutically acceptable salts of the claimed compound, a pharmaceutical composition containing a therapeutically effective amount and a pharmaceutically acceptable carrier, and use in treating cancer in mammals characterized by ENPP1 overexpression.

Stated Advantages

Documented Applications