Pyrimidine based modulators and uses thereof

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof wherein:
• B is selected from a 7-to 15-membered heterocycle and C7-C15 carbocycle, wherein the 7-to 15-membered heterocycle and C7-Cis carbocycle are each optionally substituted with one or more substituents independently selected from halogen, —CN, —NO2, ═O, —N(R21)2, —B(OR21)2, —OR21, —SR21, —S(O)2(R21), —S(O)2N(R21)2, —NR21S(O)2R21, —C(O)N(R21)2, —C(O)NR21OR21, —N(R21)C(O)R21, —N(R21)C(O)N(R21)2, —N(R21)C(O)OR21, —C(O)R21, C(O)OR21, —OC(O)R21, —OC(O)N(R21)2, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbocycle and 5-to 12-membered heterocycle;
• R1 is selected from hydrogen and 5-to 15-membered heterocycle, wherein the 5-to 15-membered heterocycle is optionally substituted with one or more substituents independently selected from halogen, —B(OR20)2, —OR20, —SR20, —S(O)2(R20), —S(O)2N(R20)2, —S(O)N(R20)2, —S(O)R20(═NR20), —NR20S(O)2R20, —C(O)N(R20)2, —C(═NR20)N(R20)2, —C1-6 alkyl(═NOR20), —C(O)NR20OR20, —N(R20)C(O)R20, —N(R20)C(O)N(R20)2, —N(R20)C(O)OR20, —N(R20)2, —C(O)R20, —C(O)OR20, —OC(O)R20, —OC(O)N(R20)2, —NO2, ═O, ═N(R20), ═NO(R20), —CN, —NHCN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl-SO2R20, C1-6 alkoxyalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbocycle and 5-to 12-membered heterocycle, wherein the C3-C12 carbocycle and 5-to 12-membered heterocycle are each optionally substituted independently with one or more R1*;
• each R1* is independently selected from halogen, —B(OR20)2, —OR20, —SR20, —S(O)2(R20), —S(O)2N(R20)2, —S(O)N(R20)2, —S(O)R20(═NR20), —NR20S(O)2R20, —C(O)N(R20)2, —C(O)NR20OR20, —N(R20)C(O)R20, —N(R20)C(O)N(R20)2, —N(R20)C(O)OR20, —N(R20)2, —C(O)R20, —C(O)OR20, —OC(O)R20, —OC(O)N(R20)2, —NO2, ═O, ═N(R20), ═NO(R20), —CN, —NHCN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-C12 carbocycle;
• Y is —O—;
• R2 is selected from heterocycle, -L-heterocycle, -L-N(R23)2, and -L-aryl, wherein the heterocycle, and the heterocycle portion of -L-heterocycle are each optionally substituted with one or more R6, and wherein the aryl of the -L-aryl is optionally substituted with one or more R7;
• R3 is selected from hydrogen, halogen, —CN, —NO2, —N(R20)2, —OR20, —SR20, —S(O)2(R20), —S(O)2N(R20)2, —S(O)N(R20)2, —S(O)R20(═NR20), —NR20S(O)2R20, —C(O)N(R20)2, —N(R20)C(O)R20, —N(R20)C(O)N(R20)2, —N(R20)C(O)OR20, —C(O)R20, —C(O)OR20, —OC(O)R20, —OC(O)N(R20)2, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbocycle and 5-to 12-membered heterocycle;
• each R4 is independently selected from halogen, —NO2, ═O, ═S, —CN, C1-6 alkyl, C2-6 alkynyl, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 alkoxy, C1-6 cyanoalkyl, C1-6 hydroxyalkyl, and C1-6 haloalkyl;
• n is selected from 0, 1, 2, 3, and 4;
• each R5 is independently selected from hydrogen and C1-C6 alkyl;
• each R6 is independently selected from halogen, hydroxy, C1-C3 hydroxyalkyl, C1-C3 alkyl, oxo, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, ═CH2, ═NO—C1-C3 alkyl, C1-C3 aminoalkyl, —N(R5)S(O)2(R5), -Q-phenyl, -Q-phenylSO2F, —NHC(O)phenyl, —NHC(O)phenylSO2F, C1-C3 alkyl substituted pyrazolyl, —C1-C3 alkyl-N(R5)2, —C(O)N(R5)2, —C1-C3 alkyl-N(R5)2, —C(O)N(R5)2, tert-butyldimethylsilyloxyCH2—, —N(R5)2, (C1-C3 alkoxy)C1-C3 alkyl-, (C1-C3 alkyl)C(═O), oxo, (C1-C3 haloalkyl)C(═O)—, —SO2F, (C1-C3 alkoxy)C1-C3 alkoxy, —CH2OC(O)N(R5)2, —CH2NHC(O)OC1-C6 alkyl, —CH2NHC(O)N(R5)2, —CH2NHC(O)C1-C6 alkyl, —CH2(pyrazolyl), —CH2NHSO2C1-C6 alkyl, —CH2OC(O)heterocycle, —OC(O)N(R5)2, —OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl), —OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl)phenyl(C1-C3 alkyl)N(CH3)2, —OC(O)NH(C1-C3 alkyl)O(C1-C3 alkyl)phenyl, —OC(O)heterocycle, —O—C1-C3 alkyl, —S(O)2(R20), —S(O)2N(R20)2, —S(O)N(R20)2, —S(O)R20(═NR20), —NR20S(O)2R20, and —CH2 heterocycle, wherein the phenyl of —NHC(O)phenyl and —OC(O)NH(C1-C3 alkyl)(C1-C3 alkyl)phenyl are optionally substituted with one or more substituents selected from —C(O)H and OH, and wherein the alkyl of —O—C1-C3 alkyl is optionally substituted with substituents selected from heterocycle, oxo and hydroxy;
• and wherein the heterocycle of —CH2 heterocyclyl is optionally substituted with oxo;
• each Q is selected from a bond, S, and O;
• each R7 is independently selected from halogen, hydroxy, HC(═O)—, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, —C1-C3 alkyl-N(R5)2, —C(O)N(R5)2, and —N(R5)2;
• each L is independently selected from a C1-C4 alkylene optionally substituted with one or more substituents independently selected from halogen, hydroxy, C1-6 alkoxy, C1-C4 hydroxyalkyl, C1-C4 alkyl, C3-C6 carbocycle, and 3-to 8-membered heterocycle, wherein the C3-C6 carbocycle and 3-to 8-membered heterocycle are each optionally substituted with one or more substituents independently selected from halogen, —OH, —NO2, ═O, ═S, —CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 haloalkyl;
• and wherein optionally two substituents on the same carbon atom of L come together to form a C3-C6 carbocycle or 3-to 8-membered heterocycle, wherein the C3-C6 carbocycle and 3-to 8-membered heterocycle are each optionally substituted with one or more substituents independently selected from halogen, —OH, —NO2, ═O, ═S, —CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, and C1-6 haloalkyl;
• each R20 is independently selected from hydrogen;
• and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3-to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OH, —CN, —NO2, —NH2, —N(C1-6 alkyl)2, C1-10 alkyl, —C1-10 haloalkyl, —O—C1-10 alkyl, oxo, C3-12 carbocycle, and 3-to 12-membered heterocycle;
• each R21 is independently selected from hydrogen;
• and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3-to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OH, —CN, —NO2, —NH2, —N(C1-6 alkyl)2, C1-10 alkyl, —C1-10 haloalkyl, —O—C1-10 alkyl, oxo, C3-12 carbocycle, and 3-to 12-membered heterocycle;
• and
• each R23 is independently selected from hydrogen;
• and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3-to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OH, —CN, —NO2, —NH2, —N(C1-6 alkyl)2, C1-10 alkyl, —C1-10 haloalkyl, —O—C1-10 alkyl, oxo, C3-12 carbocycle, and 3-to 12-membered heterocycle.