Inhibitors of cysteine proteases and methods of use thereof
Inventors
Arnold, Lee D. • Jennings, Andy • Keung, Walter
Assignees
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Publication Number
US-12145911-B2
Publication Date
2024-11-19
Expiration Date
Abstract
The disclosure provides compounds with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease.
Core Innovation
The disclosure provides chemical structure representations for multiple related compounds and defines the compounds through embedded image structures with corresponding TIF, CDX, and MOL files and internal identifiers. The structures share common heterocyclic, amide or urea-like, and bicyclic or fused ring features, with recurring nitrile, carbonyl, and nitrogen-containing motifs across the series. The content emphasizes structure-file mappings for compound identification rather than additional descriptive parameters.
The described compounds include viral protease inhibitor candidates and related analogs with indole-, indazole-, pyrrolidine-, piperidyl-, azaspiro-, bicyclic lactam-, and other heteroaromatic or heterocyclic scaffold elements. Variations across the compounds include halogen, fluorinated, methoxy, alkoxy, cyano, and other substituent patterns, together with stereochemical differences. The disclosure repeatedly ties each compound to its specific structural depiction and corresponding internal identifiers.
The material also includes synthetic and characterization information for selected compounds, including coupling, deprotection, cyano installation, purification, and analytical confirmation by MS, 1H NMR, prep-HPLC, prep-SFC, and LC-MS. In the portions describing biological evaluation, the disclosure references SARS-CoV-2 Mpro enzymatic inhibition and HCoV 229E and HCoV OC43 cytopathic effect assays. The overall presentation connects the defined compound structures to synthetic examples, characterization data, and documented assay contexts.
Claims Coverage
The provided claim set is centered on compounds represented by embedded chemical structure representations. Across the independent claim material present in the inputs, the inventive content is the definition of the compound by reference to specific structure files and embedded images, typically in TIF, CDX, and MOL formats with internal identifiers. No additional substantive chemical limitations are explicitly stated in the independent claim text provided.
Compound represented by embedded chemical structure files
A compound is defined by a chemical structure shown in provided embedded image and structure files, with references to TIF, CDX, and MOL formats and corresponding internal identifiers.
Compound represented by embedded chemical structure images
A compound is defined by the chemical structure shown in embedded image files, with the representation tied to specific file-format references and internal identifiers.
Substituent-variable scaffold definitions
A compound is defined through substituent-variable scaffold language, including R_G3 selected among H, C1-6 alkyl, C3-6 cycloalkyl, phenyl, and heterocycles, and R_G2 selected between anilide/amine and carbamoyl forms with defined R_m options.
General formula families with constrained substituent sets
The disclosed compounds are described by general structural families such as II-D-A/II-D-B, II-E-A/II-E-B, II-F, II-G, II-H-A/II-H-B, II-I, with substituent variables including R1, R2, R3, RB, Rxy, A, RD, RE, pp, ss, and mm.
Representation of viral protease inhibitor compounds
The claimed compounds are described in the inputs as viral protease inhibitor compounds whose definitions are tied to specific embedded chemical structure representations and associated identifiers.
Overall, the claim coverage is dominated by compounds defined through embedded chemical structure representations and file-based identifiers, with additional coverage in the inputs describing substituent-variable compound families. No additional substantive functional limitations are explicitly provided in the consolidated claim excerpts.
Stated Advantages
Broad-spectrum anti-coronaviral therapeutics.
Provides embedded chemical structure representations for related small molecules, enabling compounds to be represented by the chemical structures.
Documented Applications
Treatment or therapeutic use directed to coronaviruses including SARS, MERS, and SARS-CoV-2 via cysteine protease inhibition.
SARS-CoV-2 Mpro enzymatic inhibition evaluation.
HCoV 229E cytopathic effect assay evaluation.
HCoV OC43 cytopathic effect assay evaluation.
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