Substituted pyrimidinones and pyrimidinthiones

A compound of Formula I,

• 75
• a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a prodrug thereof, or a pharmaceutically acceptable salt of a prodrug thereof, wherein:
• X is selected from NR3R4, OR3, CR3R5R5, C(O)R3, S(O)mR3, NR3C(O)R4, NR3S(O)mR4;
• Z is selected from —O, —S, and —NR2;
• mis 0, 1, or 2;
• Ar is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl;
• and G;
• G is selected from
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• wherein each G group may have from 0-4 substituents independently selected from halogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, —OR5, SR5, —NR5R5, —C(O)R5, —C(S)R5, —CN, —C(O)NR5R5, —C(S)NR5R5, —NR5C(O)R5, —NR5C(S)R5, —S(O)2NR5R5, —NR5S(O)2R5, NO2, aryl, substituted aryl, substituted heteroaryl;
• n is 0, 1, 2, or 3;
• R1 and R5 are independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa —S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —NRaC(S)ORa, —OC(O)NRaRa, —OC(S)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
• R2 is selected from —Ra, —S(O)mRa, —C(O)NRaRa, —C(S)NRaRa —S(O)mNRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
• R3 and R4 are independently selected from Ra, heterocycloalkyl, substituted heterocycloalkyl, substituted heteroaryl, substituted aryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, or substituted heteroaryl heterocycloalkyl provided that when Ar is not G at least one of R3 or R4 are heteroaryl, substituted heteroaryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, substituted heteroaryl heterocycloalkyl, heterocycloalkyl or substituted heterocycloalkyl;
• Raeach is selected from H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, or heterocycloalkyl optionally substituted with 1 to 5 of Rt, —ORt, —S(O)mRt, NRtRt, oxo (═O), thione (═S), phenyl, heteroaryl, or heterocycloalkyl where phenyl, heteroaryl, and heterocycloalkyl are optionally substituted with 1 to 5 independently taken from Rt;
• and
• Rt each is selected from H, halogen, —NO2, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)-NHalkyl, —C(O)Nalkylalkyl, —Oalkyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, alkyl, cycloalkyl, haloalkyl, phenyl, benzyl, heteroaryl, or heterocycloalkyl where phenyl, benzyl heteroaryl and heterocycloalkyl may be optionally substituted with alkyl or halogen.