Pyrimidine compounds, compositions, and medicinal applications thereof

A compound of Formula I:

• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
• X is —NH— or —O—;
• R1 is —(C(R4)2)nR5, wherein R5 is substituted with 2 or 3 R5′;
• n is 0, 1, 2, or 3;
• each R4 is independently hydrogen, alkyl, halo, haloalkyl, hydroxy, alkoxy, or heteroalkyl;
• R5 is C4-10cycloalkyl, aryl, or heteroaryl;
• each R5′ is independently deuterium, aryl, heteroaryl, alkyl, C3-C6 cycloalkyl, 3-8 membered heterocycloalkyl, oxo, halo, heteroalkyl, haloalkyl, cyano, hydroxy, amino, —NH2, —NHR6, —N(CH3)R6, —N(R6)2, —C(═O)NH2, —C(═O)NHR6, —C(═O)N(R6)2, —NR6C(═O)R6, —NHC(═O)R6, —S(═O)2alkyl, —S(═O)2aryl, —S(═O)2NH2, —S(═O)2NHR6, —S(═O)2N(R6)2, —S(═O)2heteroaryl, alkoxy, or haloalkoxy;
• or
• two adjacent R5′ groups come together to form a 5- to 10-membered heterocycle, wherein the 5- to 10-membered heterocycle is unsubstituted or substituted with alkyl;
• each R6 is independently alkyl, aminoalkyl, cycloalkyl, aryl, or heteroaryl;
• R2 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is substituted with at least one R7 and 0, 1, or 2 R8;
• each R7 is independently
• Y is —C(═O)—, —S(═O)—, or —S(═O)2—;
• R9, R9′, and R9″ are independently hydrogen, deuterium, halo, alkyl, haloalkyl, cycloalkyl, heteroalkyl, or (alkyl)heterocycloalkyl;
• R10 is hydrogen, alkyl, haloalkyl, or cycloalkyl;
• each R8 is independently aryl, heteroaryl, alkyl, cycloalkyl, heterocycloalkyl, halo, heteroalkyl, haloalkyl, cyano, hydroxy, amino, —N(R11)2, —S(═O)2alkyl, —S(═O)2aryl, —S(═O)2heteroaryl, or alkoxy;
• each R11 is independently alkyl, cycloalkyl, aryl, or heteroaryl;
• R3 is heteroaryl substituted with 0, 1, 2, or 3 R12;
• each R12 is independently aryl, heteroaryl, alkyl, heteroalkyl, haloalkyl, halo, cyano, alkoxy, heterocycloalkyl, —N(R13)2, —S(═O)2NH2, —S(═O)2alkyl, —S(═O)2aryl, —S(═O)2heteroaryl, or cycloalkyl, wherein the aryl, heteroaryl, heterocycloalkyl, or cycloalkyl are each independently unsubstituted or substituted with 0, 1, or 2 R14;
• each R13 is independently hydrogen, alkyl, cycloalkyl, aryl, or heteroaryl;
• each R14 is independently deuterium, aryl, heteroaryl, alkyl, cycloalkyl, heterocycloalkyl, halo, heteroalkyl, haloalkyl, cyano, hydroxy, amino, —N(R11)2, —S(═O)2alkyl, —S(═O)2aryl, —S(═O)2heteroaryl, or alkoxy;
• and
• each R15 is independently alkyl, cycloalkyl, aryl, or heteroaryl.