Compounds and methods for the treatment of malaria

A pharmaceutical composition comprising a therapeutically effective amount of a compound having the structure:

• wherein the dotted line represents an optional double bond;
• m is 0 or 1;
• n is 0, 1, or 2;
• A is CH or N;
• X is absent or —C≡C—;
• R1 is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C6-C10 aryl, or C2-C9 heteroaryl;
• Y is C1-C6 alkylene;
• R2 is C1-C6 perfluoroalkyl, C6-C10 aryl, C6-C10 aryl C1-C6 alkyl, C3-C10 carbocyclyl, or C2-C9 heteroaryl, wherein R2 is not 2-methoxyphenyl;
• Z is absent, C1-C6 alkylene, or C1-C6 heteroalkylene;
• R3 is hydrogen, hydroxyl, —NR5R6, —C(O)R7, or C2-C9 heterocyclyl;
• R4 is hydrogen or C1-C6 alkyl;
• R5 and R6 are independently hydrogen, C1-C6 alkyl, or C1-C6 acyl;
• and
• R7 is hydroxyl, C1-C6 heteroalkyl, or C2-C9 heterocyclyl;
• or a pharmaceutically acceptable salt thereof;
• and
• a pharmaceutically acceptable excipient.

A method of preventing or treating malaria in a subject, comprising the step of administering to the subject an effective amount of a compound having the structure:

• wherein the dotted line represents an optional double bond;
• m is 0 or 1;
• n is 0, 1, or 2;
• A is CH or N;
• X is absent or —C≡C—;
• R1 is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C6-C10 aryl, or C2-C9 heteroaryl;
• Y is C1-C6 alkylene;
• R2 is C1-C6 perfluoroalkyl, C6-C10 aryl, C6-C10 aryl C1-C6 alkyl, C3-C10 carbocyclyl, or C2-C9 heteroaryl, wherein R2 is not 2-methoxyphenyl;
• Z is absent, C1-C6 alkylene, or C1-C6 heteroalkylene;
• R3 is hydrogen, hydroxyl, —NR5R6, —C(O)R7, or C2-C9 heterocyclyl;
• R4 is hydrogen or C1-C6 alkyl;
• R5 and R6 are independently hydrogen, C1-C6 alkyl, or C1-C6 acyl;
• and
• R7 is hydroxyl, C1-C6 heteroalkyl, or C2-C9 heterocyclyl;
• or a pharmaceutically acceptable salt thereof.