Anti-viral compounds

Inventors

Vandyck, Koen • Bardiot, Dorothée Alice Marie-Eve • Raboisson, Pierre Jean-Marie Bernard • Beigelman, Leonid • Stoycheva, Antitsa Dimitrova • Boland, Sandro • Marchand, Arnaud Didier Marie

Assignees

Katholieke Universiteit Leuven • Aligos Therapeutics Inc

Abstract

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

Core Innovation

The invention relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, defined by Ring A1 and multiple substituent variables R1 through R9 with specific structural selections and substitution patterns. Ring A1 is selected from defined ring options and is optionally substituted with deuterium, halogen, hydroxy, an unsubstituted C1-4 alkyl, or an unsubstituted C1-4 haloalkyl; R1 is cyano, and R2 and R4 are hydrogen or deuterium. The framework further defines R3 as an unsubstituted or substituted monocyclic nitrogen-containing heterocyclyl(C1-4 alkyl) or bicyclic nitrogen-containing heterocyclyl(C1-4 alkyl), together with R5, R8, and R9 as specified structural classes with substitution limits.

The disclosed compound families include chiral complex heterocycle-containing compounds, including tetrahydropyrazolo[1,5-a]pyrimidine derivatives, azatricyclo[5.2.1.0{circumflex over (2,6)}]dec-8-ene core motifs, and related scaffolds bearing cyano-containing side chain features and bicyclic or pyrrolidinyl amide motifs. The reported examples include specific compound structures and stereoisomers, with analytical characterization by LC-MS, 1H NMR, yields, and purified products. The described examples also include compounds incorporating fluorinated amino-acid acyl groups, 2-oxopyrrolidinylpropanamide motifs, pyridin-2-ylformamide and pyrazin-2-ylformamide substituents, and late-stage installation of substituents.

The invention further concerns compounds useful in coronavirus-related contexts, including selective inhibition of a coronavirus protease compared to Cathepsin L and treatment of coronavirus infection. The claim context also includes compound administration for coronavirus infection and protease inhibition in coronavirus-infected cells, and the provided content references selectivity assessment against Cathepsin L and additional use context involving coronavirus/picornavirus/norovirus infections.

Claims Coverage

The provided claim set centers on one independent compound claim to a Formula (I) compound or pharmaceutically acceptable salt thereof, with defined Ring A1 selection and substituent variables R1 through R9. Four inventive feature groups are consistently repeated across the inputs: the Formula (I) scaffold with cyano R1 and optional Ring A1 substitution, the heterocyclyl and hydrocarbon substituent constraints at R3, R5, R8, and R9, and the coronavirus-related use claims including treatment and selective protease inhibition versus Cathepsin L.

Claim coverage is dominated by the Formula (I) structural definition, especially the cyano R1 position, the defined Ring A1 options, and the constrained R3/R5/R8/R9 substituent classes. The remaining claim coverage is directed to treatment of coronavirus infection and selective inhibition of a coronavirus protease versus Cathepsin L.

Stated Advantages

Documented Applications