Antimalarial agents

A compound having the structural Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• U is N or CH, wherein when U is N, X, Y and Z are CH;
• X is N or CH, wherein when X is N, U, Y and Z are CH;
• Y is N or CH, wherein when Y is N, X, U and Z are CH;
• Z is N or CH, wherein when Z is N, X, Y and U are CH;
• R1 is selected from the group consisting of
• wherein said group is optionally substituted with-from 1 to 5 substituents independently selected from halogen, CN, OH, alkoxy, C1-C6alkylOC1-C6alkyl, C1-C6alkylCOOH, COOH, oxo, COOC1-C6alkyl, phenyl, C3-C6cycloalkyl, C1-C6alkyl, haloC1-C6alkyl, C1-C6alkylOH, CON(R7)(R8), N(R7)(R8) and C1-C6alkylN(R7)(R8);
• C1-C6alkylCOOH, COOH, oxo;
• R2 is hydrogen, C1-C6alkylCOOH, COOH, C3-C6cycloalkyl, C1-C6alkyl, haloC1-C6alkyl or C1-C6alkylOH;
• R3 is halogen, CN, OH, alkoxy, C1-C6alkylOC1-C6alkyl, C1-C6alkylCOOH, COOH, C3-C6cycloalkyl, C1-C6alkyl, haloC1-C6alkyl, C1-C6alkylOH, CON(R7)(R8), N(R7)(R8) or C1-C6alkylN(R7)(R8);
• R4 is hydrogen, halogen, CN, C1-C6alkylCN, OH, alkoxy, C1-C6alkylOC1-C6alkyl, C1-C6alkylOhaloC1-C6alkyl, C1-C6alkylOC1-C6alkylOC1-C6alkyl, C1-C6alkylCOOH, COOH, C1-C6alkylSO2C1-C6alkyl, C1-C6alkylphenyl, phenyl, heterocycloalkyl, C1-C6alkylheterocycloalkyl, heteroaryl, C1-C6alkylheteroaryl, C3-C6cycloalkyl, C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, haloC1-C6alkyl, C1-C6alkylOH, CON(R7)(R8), N(R7)(R8), C1-C6alkyl (OCH2CH2)mN3, or C1-C6alkylN(R7)(R8), wherein the C1-C6alkylphenyl, phenyl, heterocycloalkyl, C1-C6alkylheterocycloalkyl, heteroaryl, C1-C6alkylheteroaryl, C1-C6alkylOC1-C6alkyl, C1-C6alkylOH or C3-C6cycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of halogen, CN, OH, alkoxy, C1-C6alkylOC1-C6alkyl, C1-C6alkylCOOH, COOH, oxo, COOC1-C6alkyl, C1-C6alkyl, haloC1-C6alkyl, C1-C6alkylOH, SO2C1-C6alkyl, C1-C6alkySO2C1-C6alkyl, OSO2F, CON(R7)(R8), N(R7)(R8) and C1-C6alkylN(R7)(R8);
• R5 is hydrogen, halogen, CN, OH, alkoxy, C1-C6alkylOC1-C6alkyl, C1-C6alkylCOOH, COOH, phenyl, C1-C6alkylC3-C6cycloalkyl, C3-C6cycloalkyl, C1-C8alkyl, haloC1-C6alkyl, C1-C6alkylOH, CON(R7)(R8), N(R7)(R8) or C1-C6alkylN(R7)(R8) or when taken with R6 forms a C3-C6cycloalkyl or C3-C6heterocycloalkyl or when R5 is C1-C8alkyl and R1 is a heterocycloalkyl or C3-C12cycloalkyl, R5 optionally bonds to R1 to form a macrocycle;
• R6 is hydrogen, halogen, CN, OH, alkoxy, C1-C6alkylOC1-C6alkyl, C1-C6alkylCOOH, COOH, phenyl, C1-C6alkylC3-C6cycloalkyl, C3-C6cycloalkyl, C1-C8alkyl, haloC1-C6alkyl, C1-C6alkylOH, CON(R7)(R8), N(R7)(R8) or C1-C6alkylN(R7)(R8) or when taken with R5 forms a C3-C6cycloalkyl or C3-C6heterocycloalkyl;
• R7 is hydrogen, C1-C6alkylCOOH, COOH, C3-C6cycloalkyl, C1-C6alkyl, haloC1-C6alkyl or C1-C6alkylOH;
• R8 is hydrogen, C1-C6alkylCOOH, COOH, C3-C6cycloalkyl, C1-C6alkyl, haloC1-C6alkyl or C1-C6alkylOH;
• R9 is hydrogen, halogen, or C1-C6alkyl;
• m is 1, 2 or 3;
• and
• n is 0, 1, 2 or 3.