Anti-fungals compounds targeting the synthesis of fungal sphingolipids

A method of inhibiting fungal sphingolipid synthesis in a fungus comprising contacting the fungus with an effective amount of the compound having the structure:

• wherein
• R1 is —H, alkyl, alkenyl, or alkynyl;
• R2 is —H, alkyl, alkenyl, or alkynyl;
• R3, R4, R5, and R6 are each independently —H, halogen, C1-C6 alkyl, —OH, —O—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2 or —OCF3, or
• R3 and R4 are each independently —H, halogen, C1-C6 alkyl, —OH, —O—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2 or —OCF3, and R5 and R6 combine to form a fused aryl or fused heteroaryl, which are each unsubstituted or substituted, or
• R3 and R6 are each independently —H, halogen, C1-C6 alkyl, —OH, —O—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2 or —OCF3, and R4 and R5 combine to form a fused aryl or fused heteroaryl, which are each unsubstituted or substitute, or
• R5 and R6 are each independently —H, halogen, C1-C6 alkyl, —OH, —O—(C4-C6 alkyl), —CHF2, —CF3, —OCHF2 or —OCF3, and R3 and R4 combine to form a fused aryl or fused heteroaryl, which are each unsubstituted or substituted;
• and
• A is an aryl or heteroaryl, which are each unsubstituted or substituted,
• wherein when R3, R4, and R6 are each —H and R5 is —OH or —OCH3, or R3, R5, and R6 are each —H and R4 is —Br, then A is other than ortho-tolyl or meta-bromophenyl, or a pharmaceutically acceptable salt or ester thereof, so as to thereby inhibit sphingolipid synthesis in the fungus.

A method of inhibiting fungal sphingolipid synthesis in a fungus in a mammal without substantially inhibiting mammalian sphingolipid synthesis comprising administering to the mammal an effective amount of the compound of having the structure:

• wherein
• R4 is —H, alkyl, alkenyl, or alkynyl;
• R2 is —H, alkyl, alkenyl, or alkynyl;
• R3, R4, R5, and R6 are each independently —H, halogen, C1-C6 alkyl, —OH, —O—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2 or —OCF3, or
• R3 and R4 are each independently —H, halogen, C1-C6 alkyl, —OH, —O—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2 or —OCF3, and R5 and R6 combine to form a fused aryl or fused heteroaryl, which are each unsubstituted or substituted, or
• R3 and R6 are each independently —H, halogen, C1-C6 alkyl, —OH, —O—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2 or —OCF3, and R4 and R5 combine to form a fused aryl or fused heteroaryl, which are each unsubstituted or substitute, or
• R5 and R6 are each independently —H, halogen, C1-C6 alkyl, —OH, —O—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2 or —OCF3, and R3 and R4 combine to form a fused aryl or fused heteroaryl, which are each unsubstituted or substituted;
• and
• A is an aryl or heteroaryl, which are each unsubstituted or substituted,
• wherein when R3, R4, and R6 are each —H and R5 is —OH or —OCH3, or R3, R5, and R6 are each —H and R4 is —Br, then A is other than ortho-tolyl or meta-bromophenyl, or a pharmaceutically acceptable salt or ester thereof, so as to thereby inhibit fungal sphingolipid synthesis in the fungus in the mammal without substantially inhibiting mammalian sphingolipid synthesis.