Compounds and compositions for the treatment of parasitic diseases

A compound of Formula I:

• or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof;
• wherein
• X1 is N or O, or NR5;
• X2 is N or NR7, provided that one of X1 and X2 is N;
• W is CR6 or N;
• L1 is a bond, —C(O)— or —S(O)2—,
• L2 is selected from a bond, —CR9a,R9b—, —NR10—, and —O—, wherein R9a is hydrogen, halo or C1-4alkyl, R9b is selected from hydrogen, halo, hydroxyl, C1-4alkyl, and C1-4alkoxy;
• and R10 is hydrogen or C1-4alkyl;
• R1 is selected from hydrogen, C1-6alkyl, C1-4alkoxy, C6-10aryl, C5-10heteroaryl, C3-7cycloalkyl, C5-6heterocycloalkyl, and C9-10heterocyclyl, wherein
• the C1-6alkyl or C1-4alkoxy is unsubstituted or substituted with 1 to 2 substituents independently selected from halo, hydroxy, C1-4alkoxy, C5-6aryloxy, hydroxycarbonyl, C1-4alkoxycarbonyl, amino, C1-4alkyamino, C1-4alkoxycarbonylamino, C5-6aryl, and C5-6heterocycloalkyl;
• and
• the C6-10aryl and C5-10heteroaryl, C3-7cycloalkyl, C5-6heterocycloalkyl or C9-10heterocyclyl is unsubstituted or substituted with 1 to 3 substituents independently selected from halo, cyano, hydroxyl, oxo, C1-4alkyl, benzyl, haloC1-4alkyl, C1-4alkoxyC1-4alkyl, C1-4alkylaminoC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, amino, C1-4alkylamino, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4alkylsulfonyl, C5-6heteroaryl, haloC5-6heteroaryl, C3-6cycloalkyl, and C5-6heterocycloalkyl;
• or —N(R2)-L1-L2-R1 together forms a nitro group;
• R2 is hydrogen, C1-4alkyl or —C(O)C5-6heteroaryl;
• R3 is hydrogen, halo or C1-4alkyl;
• R4 is selected from hydrogen, halo, C1-4alkyl, haloC1-4alkyl, C1-4alkylsulfonyl, C5-6heteroaryl, and C5-6heterocycloalkyl;
• R5 is selected from hydrogen, C1-4alkyl, —C(O)OC1-4alkyl, wherein the C1-4alkyl portion of C1-4alkyl or —C(O)OC1-4alkyl is unsubstituted or substituted by amino, C1-4alkylamino, or C5-6heterocycloalkyl;
• R6 is selected from halo, cyano, C1-4alkyl, C1-4alkenyl, C1-4alkoxy, C1-4alkylsulfonyl, C3-6cycloalkylsulfonyl, C1-4alkylphosphinyl oxide, C1-4alkylcarbonylamino, phenyl, C5-6heteroaryl, C5-6heteraryl, C4-6heterocycloalkyl, and C6-10heterocyclyl, wherein
• the C1-6alkyl, C1-4alkenyl or C1-4alkoxy of R6 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, amino, C1-4alkylamino, and hydroxyl-substituted C1-4alkylamino;
• the pheny or C5-6heteroaryl of R6 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkylaminoC1-4alkyl, aminoC1-4alkyl, C4-6heterocycloalkyC1-4alkyl, C1-4alkylsilanylC1-4alkoxyC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkoxyC1-4alkoxy, aminoC1-4alkoxy, phenylC1-4alkoxy, C5-6heteroarylC1-4alkoxy, C3-6cycloalkyC1-4alkoxy, C3-6heterocycloalkyC1-4alkoxy, C1-4alkylcarbonyl, aminocarbonyl, C1-4alkylaminocarbonyl, C1-4alkoxycarbonyl, amino, C1-4alkylamino, C4-6heterocycloalkyC1-4alkylamino, C4-6heterocycloalkyC1-4alkylamino, —NHC(O)R14 S(O)2R15, phenyl, C5-6heteraryl, C5-6heterocycloalkyl, and C9-10heterocyclyl,
• the C3-6heterocycloalkyl or C6-10heterocyclyl of R6 is unsubstituted or substituted by 1 to 2 substituents independently selected from C1-4alkyl, oxo, and C1-4alkoxycarbonyl, wherein
• R14 is selected from C1-4alkyl, aminoC1-4alkyl, amino, C1-4alkylamino, cyclopropylamino, C1-4alkoxy, C1-4alkylsulfonyl, and C1-4alkylaminosulfonyl
• R15 is selected from C1-4alkyl, amino, C3-6cycloalkyl, and C5-6heterocycloalkyl;
• and
• the phenyl, C5-6heteraryl, C5-6heterocycloalkyl or C9-10heterocyclyl substituent of the phenyl or C5-6heteroaryl of R6 is unsubstituted or substituted by 1 to 3 substituents independently selected from C1-4alkyl and oxo;
• R7 is selected from hydrogen, C1-4alkyl and —C(O)C5-6heteroaryl;
• and
• R8 is hydrogen or halo.