Methods and compositions for inhibition of dihydroorotate dehydrogenase

A compound having a formula represented by a structure:

• wherein R1 is selected from hydrogen, halogen, —SF5, —CN, —N3, —OH, —NH2, —CF3, and —CF2CF3;
• wherein one of R5a, R5b, R5c, R5d and R5e is selected from a group having formula represented by a structure:
• —R20, —R30-A1-R40, -A1-R40, -A1-R30-A2-R40, or -A1-R30-A2-R40-A3-R41;
• wherein A1 is selected from —O— and —NR50—;
• wherein R50 is selected from —C1-C10 aminoalkyl, —C1-C10 alkylamino, and —C1-C10 hydroxyalkyl;
• wherein A2 is selected from —O— and —NR6Q—;
• wherein R60 is selected from —C1-C10 aminoalkyl, —C1-C10 alkylamino, and —C1-C10 hydroxyalkyl;
• wherein A3 is selected from —O— and —NR70—;
• wherein R70 is selected from —C1-C10 aminoalkyl, —C1-C10 alkylamino, and —C1-C10 hydroxyalkyl;
• wherein R20 is selected from halogen, —C1-C10 alkylamino and —C1-C10 alkoxy;
• wherein R30 is selected from —C1-C10 alkanediyl, —C1-C10 aminoalkanediyl, and —C1-C10 hydroxyalkanediyl;
• and
• wherein each of R40 and R41 is independently selected from —C1-C10 alkyl, —C1-C10 aminoalkyl, —C1-C10 hydroxyalkyl, and —(CH2)nAr1;
• wherein n is an integer selected from 1, 2, and 3;
• and
• wherein Ar1 is a phenyl group substituted with 1, 2, or 3 groups independently selected from halogen, —SF5, —CN, —N3, —OH, —NH2, from —C1-C3 alkyl, —C1-C3 alkoxy, —C1-C3 haloalkyl, —C1-C3 aminoalkyl, —C1-C3 alkylamino, —C1-C3 haloalkylamino, —C1-C3 hydroxyalkyl, —C1-C3 halohydroxyalkyl, cycloalkyl, and heterocycloalkyl;
• and wherein four of R5a, R5b, R5c, R5d and R5e is independently selected from hydrogen, halogen, —SF5, —CN, —N3, —OH, —NH2, —CF3, and —CF2CF3;
• or a pharmaceutically acceptable salt thereof.