4-substituted-2-thiazole amides as antiviral agents

A compound having a structure represented by a formula:

• wherein n is selected from 0 and 1;
• wherein A, when present, is selected from O, NH, N(C1-C4 alkyl), and N(Ar3);
• wherein Ar3, when present, is phenyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
• wherein each of Z1, Z2, Z3, and Z4 is independently selected from N and CR10, provided that at least two of Z1, Z2, Z3, and Z4 are CR∘;
• wherein each occurrence of R10, when present, is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, —C(O)R20, —CO2R21, —C(O)NR22, —SO2R23, and Cy1;
• wherein each occurrence of R20, R21, R22, and R23, when present, is independently selected from hydrogen and C1-C4 alkyl;
• wherein Cy1, when present, is selected from 5-membered heterocycle and 6-membered heterocycle, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 thioalkyl, C1-C4 thiohaloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
• and either:
• (a) wherein Ar1 is selected from pyridinyl, piperazinyl, and 6-membered aryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, —C(O)R1, —CO2R12, —C(O)NR13, and —SO2R14;
• wherein each occurrence of R11, R12, R13, and R14, when present, is independently selected from hydrogen and C1-C4 alkyl;
• and
• wherein Ar2 is selected from 5-membered heterocycle, 6-membered heterocycle, 5-membered heteroaryl, and 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 thioalkyl, C1-C4 thiohaloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, —C(O)R15, —CO2R16, —C(O)NR17, and —SO2R18;
• and
• wherein each occurrence of R15, R16, R17, and R18, when present, is independently selected from hydrogen and C1-C4 alkyl;
• or
• (b) wherein Ar1 is a structure represented by a formula:
• wherein each of R31a, R31b, R31c, and R31d is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, —C(O)R11, —CO2R12, —C(O)NR13, and —SO2R14;
• wherein R32 is selected from —CN and —CH2NH2;
• and
• wherein Ar2 is selected from 5-membered heterocycle, 6-membered heterocycle, 5-membered heteroaryl, 6-membered heteroaryl, 6-membered aryl, and bicyclo[1.1.1]pentanyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 thioalkyl, C1-C4 thiohaloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, —C(O)R15, —CO2R16, —C(O)NR17, and —SO2R18,
• or a pharmaceutically acceptable salt thereof.