Compounds, compositions, and methods for treating fibrosis

A compound of formula (1), or a salt, solvate, enantiomer, diastereomer, or tautomer thereof:

• wherein:
• Y is selected from the group consisting of S and NH;
• A ring is
• R1 is —C(R′)(R″)—C(═O)—R1a, wherein:
• R′ and R″ are independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, and optionally substituted C3-C8 cycloalkyl, or R′ and R″ combine with the carbon atom to which they are bound to form optionally substituted C3-C8 cycloalkyl:
• R1a is selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl, optionally substituted C3-C8 cycloalkyl, and NRR, wherein each occurrence of R is independently selected from the group consisting of H and optionally substituted C1-C6 alkyl;
• R2 is selected from the group consisting of 1H-tetrazol-5-yl
• C(═O)NH—S(═O)2(C1-C6 alkyl or C3-C8 cycloalkyl), and —C(═O)NR2aR2b,
• wherein R2a is methyl and R2b is selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, —S(═O)2(C1-C6 alkyl), and —S(═O)2(C3-C8 cycloalkyl) and
• R3 is C1-C6 thioether.

A compound of formula (1), or a salt, solvate, enantiomer, diastereomer, or tautomer thereof:

• wherein:
• Y is selected from the group consisting of S and NH;
• A ring is
• R1 is —C(R′)(R″)—C(═O)—R1a, wherein:
• R′ and R″ are independently selected from the group consisting of H optionally substituted C1-C6 alkyl, and optionally substituted C3-C8 cycloalkyl, or R′ and R″ combine with the carbon atom to which they are bound to form optionally substituted C3-C8 cycloalkyl;
• R1a is selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl, optionally substituted C3-C8 cycloalkyl, and NRR, wherein each occurrence of R is independently selected from the group consisting of H and optionally substituted C1-C6 alkyl;
• R2 is selected from the group consisting of:
• 1H-tetrazol-5-yl,
• R3 is C1-C6 thioether.

A method of treating or ameliorating a Mitogen-Activated Protein Kinase Phosphatase-5 (MKP5) modulated disease or disorder in a subject,

• the method comprising administering to the subject a therapeutically effective amount of a compound of formula (1), or a salt, solvate, enantiomer, diastereomer, or tautomer thereof:
• wherein:
• Y is selected from the group consisting of S and NH;
• A ring is
• R1 is —C(R′)(R″)—C(═O)—R1a, wherein:
• R′ and R″ are independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, and optionally substituted C3-C8 cycloalkyl, or R′ and R″ combine with the carbon atom to which they are bound to form optionally substituted C3-C8 cycloalkyl;
• R1a is selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl, optionally substituted C3-C8 cycloalkyl, and NRR, wherein each occurrence of R is independently selected from the group consisting of H and optionally substituted C1-C6 alkyl;
• R2 is selected from the group consisting of 1H-tetrazol-5-yl
• —C(═O)NH—S(═O)2(C1-C6 alkyl or C3-C8 cycloalkyl), and —C(═O)NR2aR2b,
• wherein R2a and R2b are independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, —S(═O)2(C1-C6 alkyl), and —S(═O)2(C3-C8 cycloalkyl),
• or R2a and R2b combine with the N atom to which they are bound to form optionally substituted 3- to 8-membered heterocyclyl or heteroaryl;
• and
• R3 is C1-C6 thioether.

A method of treating or ameliorating a Mitogen-Activated Protein Kinase Phosphatase-5 (MKP5) modulated disease or disorder in a subject,

• the method comprising administering to the subject a therapeutically effective amount of a compound of formula (1), or a salt, solvate, enantiomer, diastereomer, or tautomer thereof:
• wherein:
• Y is selected from the group consisting of S and NH;
• A ring is
• R1 is —C(R′)(R″)—C(═O)—R1a, wherein:
• R′ and R″ are independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, and optionally substituted C3-C8 cycloalkyl, or R′ and R″ combine with the carbon atom to which they are bound to form optionally substituted C3-C8 cycloalkyl;
• R1a is selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C1-C6 haloalkyl, optionally substituted C3-C8 cycloalkyl, and NRR, wherein each occurrence of R is independently selected from the group consisting of H and optionally substituted C1-C6 alkyl;
• R2 is selected from the group consisting of:
• 1H-tetrazol-5-yl,
• R3 is C1-C6 thioether.