Anti-fungals targeting the synthesis of fungal shingolipids

A method of (a) inhibiting the growth of a fungus;

• (b) inhibiting fungal shingolipid synthesis in a fungus;
• or
• (c) inhibiting fungal shingolipid synthesis in a fungus in a mammal without substantially inhibiting mammalian shingolipid synthesis comprising contacting the fungus with an effective amount of a compound having the structure:
• wherein
• R1 is H, alkyl, alkenyl, or alkynyl;
• R2 is H, alkyl, alkenyl, or alkynyl;
• R3, R4, R5, R6, and R7 are each independently —H, halogen, CN, —CF3, —OCF3, —NO2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OH, —OAc, —OR13, —COR13, —SH, —SR13, —SO2R13, —NH2, —NHR13, —NR14R15, —NHCOR12, or —CONR14R15;
• R8 and R9 are each independently —H, halogen, —CN, —CF3, —OCF3, —NO2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OH, —OAc, —OR13, —COR13, —SH, —SR13, —SO2R13, —SO2NR14R15, —NH2, —NHR13, NR14R15, —NHCOR12, or —CONR14R15;
• R10 is —H, halogen, —CN, —CF3, —OCF3, —NO2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OH, —OAc, —OR13, —COR13, —SH, —SR13, —SO2R13, —SO2NR14R15, —NH2, —NHR13, —NHCOR12, or —CONR14R15;
• and
• R11 and R12 are each independently —H, halogen, —CN, —CF3, —OCF3, —NO2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OH, —OAc, —OR13, —COR13, —SH, —SR13, —SO2R13, —SO2NR14R15, —NH2, —NHR13, NR14R15, —NHCOR12, or —CONR14R15,
• wherein each occurrence of R13 is independently alkyl, alkenyl, alkynyl, aryl, or heteroaryl,
• wherein each occurrence of R14 is independently —H, alkyl, alkenyl, alkynyl, aryl, or heteroaryl,
• wherein each occurrence of R15 is independently —H, alkyl, alkenyl, alkynyl, aryl, or heteroaryl,
• when R1, R2, R3, R4, R5, R6, R8, R11, R12 are each —H, R9 is —Br, and —R10 is —OH or —OCH3, then R7 is other than —CH3;
• and
• when R1, R2, R3, R4, R5, R8, R9, R11, and R12 are each —H, and —R10 is OH, then R6 and R7 are other than —H and —CH3 or —Br and H, respectively,
• or a pharmaceutically acceptable salt or ester thereof, so as to thereby inhibit the growth of the fungus.

A method of inhibiting the growth of or killing a fungus in a subject afflicted with a fungal infection comprising administering to the subject an effective amount of a compound having the structure:

• wherein
• R1 is H, alkyl, alkenyl, or alkynyl;
• R2 is H, alkyl, alkenyl, or alkynyl;
• R3, R4, R5, R6, and R7 are each independently —H, halogen, CN, —CF3, —OCF3, —NO2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OH, —OAc, —OR13, —COR13, —SH, —SR13, —SO2R13, —NH2, —NHR13, —NR14R15, —NHCOR12, or —CONR14R15;
• R8 and R9 are each independently —H, halogen, —CN, —CF3, —OCF3, —NO2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OH, —OAc, —OR13, —COR13, —SH, —SR13, —SO2R13, —SO2NR14R15, —NH2, —NHR13, NR14R15, —NHCOR12, or —CONR14R15;
• R10 is —H, halogen, —CN, —CF3, —OCF3, —NO2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OH, —OAc, —OR13, —COR13, —SH, —SR13, —SO2R13, —SO2NR14R15, —NH2, —NHR13, —NHCOR12, or —CONR14R15;
• and
• R11 and R12 are each independently —H, halogen, —CN, —CF3, —OCF3, —NO2, alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OH, —OAc, —OR13, —COR13, —SH, —SR13, —SO2R13, —SO2NR14R15, —NH2, —NHR13, NR14R15, —NHCOR12, or —CONR14R15,
• wherein each occurrence of R13 is independently alkyl, alkenyl, alkynyl, aryl, or heteroaryl,
• wherein each occurrence of R14 is independently —H, alkyl, alkenyl, alkynyl, aryl, or heteroaryl,
• wherein each occurrence of R15 is independently —H, alkyl, alkenyl, alkynyl, aryl, or heteroaryl,
• when R1, R2, R3, R4, R5, R6, R8, R11, R12 are each —H, R9 is —Br, and —R10 is —OCH3, then R7 is other than —CH3;
• and
• when R1, R2, R3, R4, R5, R8, R9, R11, and R12 are each —H, and —R10 is OH, then R6 and R7 are other than —H and —CH3 or —Br and H, respectively,
• or a pharmaceutically acceptable salt or ester thereof, so as to thereby inhibiting the growth of or kill the fungus in the subject afflicted with the fungal infection.