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-11312704-B2
Publication Date
2022-04-26
Expiration Date
Abstract
The disclosure provides compounds, such as compounds of Formula II, 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 invention relates to a compound represented by a defined structural formula in which R1a and R2 are joined together to form, together with the carbon to which they are attached, a 4-10 membered monocyclic or bicyclic heterocycle having a ring nitrogen NRG. The heterocycle is optionally substituted on a free carbon by one, two or three substituents each selected from RA, and the compound includes specified variable groups such as R1b, R3, Rt, RG, and Rm, together with pharmaceutically acceptable salts thereof.
RG is defined as C(=O)-C1-6 alkyl, optionally substituted by one, two or three substituents independently selected from halo, cyano, —NRmRm, —NRm(C(=O)Rm), phenyl, cycloalkyl, heterocycle, and C1-C6 alkoxy. RA is independently selected from halogen, C1 alkyl and C3 cycloalkyl, while Rm is H or C1 alkyl optionally substituted by halo, phenyl optionally substituted by halo, C3-6 cycloalkyl, and 5-6 membered heteroaryl. R3 is H or methyl, and Rt is H or methyl or, together with the carbon to which it is attached, forms C3-C6 cycloalkyl.
A second independent compound definition is provided for a compound in which RB is C1-C8 alkyl substituted by —NH—C(O)—C1 alkyl, wherein the C1 alkyl of —NH(O)C1 alkyl is substituted by three halogens, and the scope includes pharmaceutically acceptable salts. The disclosure also depicts specific compound examples with stereochemical variation and substituent variation across the same heterocycle-containing scaffold.
Claims Coverage
The consolidated claim coverage includes two independent claims. They cover 2 inventive feature groupings: an NRG-containing 4-10 membered monocyclic or bicyclic heterocycle scaffold with defined substituent patterns, and a separate halogen-substituted —NH—C(O)—C1 alkyl motif on a C1-C8 alkyl group; together, the claims cover both themes plus pharmaceutically acceptable salts.
NRG-containing 4-10 membered monocyclic or bicyclic heterocycle scaffold
R1a and R2 are joined together to form, together with the carbon to which they are attached, a 4-10 membered monocyclic or bicyclic heterocycle having a ring nitrogen NRG, optionally substituted on a free carbon by one, two or three substituents each selected from RA.
Defined substituent set for the heterocycle scaffold
RG is C(=O)-C1-6 alkyl optionally substituted by halo, cyano, —NRmRm, —NRm(C(=O)Rm), phenyl, cycloalkyl, heterocycle, and C1-C6 alkoxy; RA is selected from halogen, C1 alkyl and C3 cycloalkyl; Rm is H or C1 alkyl optionally substituted by halo, phenyl optionally substituted by halo, C3-6 cycloalkyl, and 5-6 membered heteroaryl; and R3 is H or methyl, with Rt H or methyl or forming C3-C6 cycloalkyl.
Halogen-substituted —NH—C(O)—C1 alkyl motif
RB is C1-C8 alkyl substituted by —NH—C(O)—C1 alkyl, wherein the C1 alkyl of —NH(O)C1 alkyl is substituted by three halogens, with coverage extending to pharmaceutically acceptable salts.
Overall, the claim set covers compounds defined by a ring-nitrogen-containing 4-10 membered monocyclic or bicyclic heterocycle with specified optional substitution patterns and a separate halogenated —NH—C(O)—C1 alkyl structural motif, both including pharmaceutically acceptable salts.
Stated Advantages
Documented Applications
No documented applications found
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