Compounds having n-arylpyrimidin-2-amine derivatives as therapeutic agents

A compound of Formula I:

• or a pharmaceutically acceptable salt, solvate, enantiomer, stereoisomer, or a tautomer thereof, wherein:
• X is H, halogen, or OH, provided that when R4 is unsubstituted phenyl and X is H then R1 is C(O)OR6;
• R1 is selected from —CN, —NO2, —C(O)NHR6, C(O)N(R6)2, —C(O)OR6, —S(O)2C1-6 alkyl or a monocyclic heteroaryl comprising one or more heteroatoms independently selected from N, S, and O, wherein the heteroaryl is optionally substituted with one or more substituents selected from —OH, oxo, halogen, C1-4 alkoxy, C1-6 alkyl, C2-6 alkenyl, or 4-7 membered monocyclic heterocycloalkyl, wherein the alkyl or alkoxy is further optionally substituted with one or more substituents selected from halogen, —NH2, —N(C1-C6 alkyl)2, —OH, —COOC1-4 alkyl, —COOH, —CONH2 or 4-7 membered monocyclic heterocycloalkyl;
• R2 is H or C1-4 alkyl;
• or
• R2 and R8 together with the atoms to which they are attached and any intervening atoms, form a 5- to-6-membered heterocycle;
• R3 is H;
• or
• R3 and R8 together with the atoms to which they are attached and any intervening atoms, form a 5- to-6-membered cycloalkyl;
• R4 is selected from —(CH2)m-aryl, —(CH2)m-heteroaryl, heterocyclyl, wherein the aryl, heteroaryl, or heteroaryl is optionally substituted with one or more R8;
• each R5 is independently selected from halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 halogenalkyl, oxy C1-6 alkyl, —S(O)2—C1-6 alkyl, —S(O)2—C2-6 alkenyl, —C(O)NH2, —C(O)NH(C1-6 alkyl), —C(O)N(C1-6 alkyl)2, —CH2C(O)NH2, —CH2C(O)NH(C1-6 alkyl), —CH2C(O)N(C1-6 alkyl)2, —NHC(O)CH3, aryl, heteroaryl;
• or
• two R5 together with the atoms to which they are attached and any intervening atoms, form 6-7 membered heterocyclyl, or 5-7 membered heteroaryl, containing at least one heteroatom selected from N, O, S;
• wherein the cycloalkyl or heterocyclyl is optionally substituted with one or more R7;
• each R6 is independently selected from H, OH, C1-6 alkyl, —S(O)2—C1-6 alkyl, C3-8 cycloalkyl, heterocyclyl, or heteroaryl, wherein the alkyl, alkoxy, heteroaryl, or heterocyclyl is optionally substituted with one or more R9;
• or
• two R6 together with the atoms to which they are attached and any intervening atoms, form 4-8-membered heterocycle;
• each R7 is independently selected from OH, halogen, C1-6 alkyl, aryl, oxy C1-6 alkyl, —CH2OC(O)C1-6 alkyl, or —CH2OCH2CH2Si(CH3)3;
• each R8 is independently selected from halogen, OH, NH2, C1-6 alkyl, —OC1-6 alkyl, —NHC1-6 alkyl, —N(C1-6 alkyl)2;
• each R9 is independently selected from halogen, OH, NH2, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• and
• m and n are integers independently selected from 0, 1, 2, 3, 4, 5 and 6;
• wherein:
• aryl is cyclic, aromatic hydrocarbon groups that have 1 to 3 aromatic rings fused or connected each other via single bond;
• heteroaryl is a monovalent monocyclic or polycyclic aromatic radical of 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, O, S, P, Se, or B, the remaining ring atoms being C;
• heterocyclyl is a saturated or partially unsaturated 3-10 membered monocyclic, 7-12 membered bicyclic (fused, bridged, or spiro rings), or 11-14 membered tricyclic ring system (fused, bridged, or spiro rings) having one or more heteroatoms independently selected from O, N, S, P, Se, or B.