Anti-fibrotic pyridinones

A compound having the structure of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is 5-10 membered heteroaryl optionally substituted with one or more R4;
• R2 is selected from the group consisting of halogen, —CN, —OR5, —SR5, —NR6R7, and —C(O)R8;
• R3 is selected from the group consisting of hydrogen, phenyl, —(CH2)n-(5-10 membered heteroaryl), —(CH2)n—(C3-10 carbocyclyl), and —(CH2)n-(3-10 membered heterocyclyl), each optionally substituted with one or more R9;
• each R4 is independently selected from the group consisting of halogen, —CN, —OH, —C(O)R8, —SO2R16, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C1-6 alkoxy, optionally substituted C6-10 aryl optionally substituted with one or more R11, C7-14 aralkyl optionally substituted with one or more R11, 5-10 membered heteroaryl optionally substituted with one or more R11, or independently two geminal R4 together are oxo;
• each R5 is independently selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C2-8 alkoxyalkyl, C6-10 aryl optionally substituted with one or more R11, C7-14 aralkyl optionally substituted with one or more R11, and —(CH2)n-(3-10 membered heterocyclyl) optionally substituted with one or more R10;
• R6 is selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C6-10 aryl optionally substituted with one or more R11, C7-14 aralkyl optionally substituted with one or more R11, (5-10 membered heteroaryl)alkyl optionally substituted with one or more R11, —C(O)R8, and —C(O)OR5;
• R7 is selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C6-10 aryl optionally substituted with one or more R1, C7-14 aralkyl optionally substituted with one or more R11, (5-10 membered heteroaryl)alkyl optionally substituted with one or more R11, —C(O)R8, and —C(O)OR5;
• or R6 and R7 together with the nitrogen to which they are attached form a 3-10 membered heterocyclyl optionally substituted with one or more R10;
• each R8 is independently selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C6-10 aryl optionally substituted with one or more R1, C7-14 aralkyl optionally substituted with one or more R11, —NR12R13, and —OR5;
• each R9 is independently selected from the group consisting of hydroxy, halogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C1-6 alkylthio, optionally substituted C2-8 alkoxyalkyl, optionally substituted C3-10 carbocyclyl, optionally substituted C6-10 aryl, —OR5, —NR14R15, —C(O)R8, —SO2R16, —CN, and —NO2;
• each R10 is independently selected from the group consisting of optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, and optionally substituted C2-6 alkynyl, or independently two geminal R10 together are oxo;
• each R11 is independently selected from the group consisting of halogen, —CN, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, —O—(CH2)n—C1-8 alkoxy, —C(O)R8, and optionally substituted C1-6 alkoxy;
• each R12 is independently selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C6-10 aryl optionally substituted with one or more R11, and C7-14 aralkyl optionally substituted with one or more R11;
• each R13 is independently selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C6-10 aryl optionally substituted with one or more R11, and C7-14 aralkyl optionally substituted with one or more R11;
• R14 is selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C6-10 aryl, and —C(O)R8;
• R15 is selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C6-10 aryl, and —C(O)R8;
• each R16 is independently selected from the group consisting of optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C6-10 aryl optionally substituted with one or more R11, C7-14 aralkyl optionally substituted with one or more R11, —NR12R13, and —OR5;
• Z is selected from oxygen and sulfur;
• each n is independently an integer from 0 to 4;
• and
• the bonds represented by a solid and dashed line are independently selected from the group consisting of a single bond and a double bond, provided that
• when R3 is H, then R1 is selected from C6-10 aryl optionally substituted with one or more R4, or 5-10 membered heteroaryl optionally substituted with one or more R4;
• when R3 is a phenyl;
• R2 is OR5 or NR6R7;
• then R1 is not triazolyl;
• when R3 is 4-methyl phenyl, R2 is morpholinyl, and Z is O;
• then R1 is not methyl;
• and
• when R3 is 4-methyl phenyl, R2 is —N(CH3)2, Z is O;
• then R1 is not methyl.