Fungal efflux pump inhibitors

A compound having the chemical formula:

• 178
• or a pharmaceutically acceptable salt thereof, wherein:
• A1 is carbon or nitrogen, provided that when A1 is nitrogen, R5 does not exist;
• R2 and R3 are independently selected from the group consisting of hydrogen, halo and —O(1C-4C)alkyl;
• R4 and R6 are independently selected from the group consisting of hydrogen, halo, —O(1C-4C)alkyl, —OCF3, and O—CH2(3C -6C)cycloalkyl;
• R5 is selected from the group consisting of hydrogen and
• 179
• R7 and R8 are independently selected from the group consisting of hydrogen, halo,
• —C≡N, —O(1C -4C)alkyl, —OCHF2, -OCF3 and, taken together, —OCH2O—;
• R1 is selected from the group consisting of -(1C-4C)alkyl, -(3C -6C)cycloalkyl, —CH2(3C -6C)alkyl and
• 180
• wherein:
• A4 is selected from the group consisting of —NH, oxygen and sulfur;
• A2, A3 and A5 are independently selected from the group consisting of carbon and nitrogen provided that no more than two of A2, A3 and A5 are nitrogen at the same time;
• or,
• R1 is —C(O)(CH2)n(R22)R9, wherein,
• n is 0, 1, 2 or3;
• R9 is selected from the group consisting of hydrogen, —OH, -(1C-4C)alkyl, -(3C-6C)cycloalkyl, —CH2(3C -6C)cycloalkyl,
• 181
• wherein:
• A6, A7 and A8 are independently selected from the group consisting of carbon, oxygen, sulfur and NR15;
• A9, A10 and A11 are independently selected from the group consisting of carbon and nitrogen;
• R10 and R11 are independently selected from the group consisting of hydrogen, -(1C-4C)alkyl, —SO2R16, —C(O)R16 and —C(O)OR16, wherein:
• R16 is selected from the group consisting of hydrogen and -(1C-4C)alkyl wherein the alkyl group may be substituted with 1, 2, 3, or 4 fluorines;
• R12 is selected from the group consisting of hydrogen, -(1C-4C)alkyl, -(3C -6C)cycloalkyl, —CH2(3C -6C)cycloalkyl, —C(O)O-(1C-4C)alkyl, —SO2R17 and —SO2NR18R19, wherein,
• R17, R18 and R19 are independently selected from the group consisting of hydrogen and -(1C-4C)alkyl;
• R14 and R15 are independently selected from the group consisting of hydrogen, -(1C-4C)alky and —NR10R11;
• R22 is selected from the group consisting of hydrogen and (1C-4C)alkyl;
• or,
• R9 is —C(R16)(R20)(CH2)pNR10OR11, wherein:
• p is 0, 1 or 2;
• R20 is selected from the group consisting of hydrogen and -(1C-4C)alkyl, the alkyl group being optionally substituted with an entity selected from the group consisting of —OH, —O(1C-4C)alkyl, —C≡N, —SO2(1C-4C)alkyl and
• 182
• and,
• the compound comprises a racemic mixture, a pure enantiomer or a pure atropisomer of either the racemic mixture or the pure enantiomer.