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Paramétrages

Paramétrages

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1. WO2020010197 - DÉRIVÉS DE PYRAZINE FUSIONNÉS EN TANT QU'INHIBITEURS D'A2A/A2B

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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What is claimed is:

1. A compound of Formula (I):


or a pharmaceutically acceptable salt thereof, wherein:

R1 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 akynyl, C1-6 haloalkyl,

C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, C(=NRe1)Rb1, C(=NRe1)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl of R1 are each optionally substituted with 1, 2, 3, or 4 independently selected R1A substituents;

each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl of Ra1, Rb1, Rc1, and Rd1 are each optionally substituted with 1, 2, 3, or 4 independently selected R1A substituents;

each Re1 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each R1A is independently selected from OH, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, and di( C1-3 alkyl)amino;

X3 is N or CR3;

R3 is selected from H, D, halo, OH, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkyl, HO-C1-3 alkyl,

C1-3 alkoxy-C1-3 alkyl, C3-5 cycloalkyl, amino, C1-3 alkylamino, di( C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 alkyl) carbamyl, carboxy, C1-3 alkylcarbonyl, C1-4 alkoxycarbonyl, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylcarbonyloxy, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(C1-3

alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, amino sulfonyl, C1-3 alkylaminosulfonyl, di(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino;

Cy1 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of Cy1 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R7 substituents;

each R7 is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa7, SRa7, NHORa7, C(O)Rb7, C(O)NRc7Rd7, C(O)NRc7(ORa7), C(O)ORa7, O C(O)Rb7, O C(O)NRc7Rd7, NRc7Rd7, NRc7NRc7Rd7, NRc7 C(O)Rb7, NRc7 C(O)ORa7, NRc7 C(O)NRc7Rd7, C(=NRe7)Rb7, C(=NOH)Rb7, C(=NCN)Rb7, C(=NRe7)NRc7Rd7, NRc7C(=NRe7)NRc7Rd7, NRc7C(=NOH)NRc7Rd7, NRc7C(=NCN)NRc7Rd7, NRc7C(=NRe7)Rb7, NRc7S(O)NRc7Rd7, NRc7S(O)Rb7, NRc7S(O)2Rb7, NRc7S(O)(=NRe7)Rb7, NRc7S(O)2NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, S(O)2NRc7Rd7, OS(O)(=NRe7)Rb7, OS(O)2Rb7, SF5, P(O)Rf7Rg7, OP(O)(ORh7)(ORi7), P(O)(ORh7)(ORi7), and BRj7Rk7, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R7 are each optionally substituted with 1, 2, 3, or 4 independently selected R7A substituents;

each Ra7, Rb7, Rc7, and Rd7 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra7, Rb7, Rc7 and Rd7 are each optionally substituted with 1, 2, 3, or 4 independently selected R7A substituents;

or, any Rc7 and Rd7, attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R7A substituents;

each Re7 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf7 and Rg7 is independently selected fromH, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh7 and Ri7 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj7 and Rk7 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj7 and Rk7 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

each R7A is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, cyano-C1-6 alkyl, HO-C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C3-5 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, carboxy, C1-6 alkylcarbonyl, C1-4 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkoxycarbonylamino, C1-6 alkylcarbonyloxy, aminocarbonyloxy, C1-6 alkylaminocarbonyloxy, di(C1-6 alkyl)aminocarbonyloxy, C1-6 alkylsulfonylamino, amino sulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6

alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;

R2 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa2, SRa2, NHORa2, C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, O C(O)Rb2, O C(O)NRc2Rd2, NRc2Rd2, NRc2NRc2Rd2, NRc2 C(O)Rb2, NRc2 C(O)ORa2, NRc2 C(O)NRc2Rd2, C(=NRe2)Rb2, C(=NOH)Rb2, C(=NCN)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2)NRc2Rd2, NRc2C(=NOH)NRc2Rd2, NRc2C(=NCN)NRc2Rd2, NRc2C(=NRe2)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2,

NRc2S (O)(=NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, OS(O)(=NRe2)Rb2, OS(O)2Rb2, SF5, P(O)Ri2Rg2, OP(O)(ORh2)(ORi2), P(O)(ORh2)(ORi2), and BRj2Rk2. wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6- 10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R2 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2A substituents;

R4 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa4, SRa4, NHORa4, C(O)Rb4, C(O)NRc4Rd4, C(O)NRc4(ORa4), C(O)ORa4, O C(O)Rb4, O C(O)NRc4Rd4, NRc4Rd4, NRc4NRc4Rd4, NRc4 C(O)Rb4, NRc4 C(O)ORa4, NRc4 C(O)NRc4Rd4, C(=NRe4)Rb4, C(=NOH)Rb4, C(=NCN)Rb4, C(=NRe4)NRc4Rd4, NRc4C(=NRe4)NRc4Rd4, NRc4C(=NOH)NRc4Rd4, NRc4C(=NCN)NRc4Rd4, NRc4C(=NRe4)Rb4, NRc4S(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)(=NRe4)Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, OS(O)(=NRe4)Rb4, OS(O)2Rb4, SF5, P(O)Rf4Rg4, OP(O)(ORh4)(ORi4), P(O)(ORh4)(ORi4), and BRj4Rk4. wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6- 10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R4A substituents;

provided that:

(a) when R2 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocyclo alkyl, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl of R2 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2A substituents;

then R4 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa4, SRa4, NHORa4, C(O)Rb4,

C(O)NRc4Rd4, C(O)NRc4(ORa4), C(O)ORa4, O C(O)Rb4, O C(O)NRc4Rd4, NRc4Rd4, NRc4NRc4Rd4, NRc4 C(O)Rb4, NRc4 C(O)ORa4, NRc4 C(O)NRc4Rd4, C(=NRe4)Rb4, C(=NOH)Rb4, C(=NCN)Rb4, C(=NRe4)NRc4Rd4, NRc4C(=NRe4)NRc4Rd4, NRc4C(=NOH)NRc4Rd4, NRc4C(=NCN)NRc4Rd4, NRc4C(=NRe4)Rb4, NRc4S(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)(=NRe4)Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, OS(O)(=NRe4)Rb4, OS(O)2Rb4, SF5, P(O)Rf4Rg4.

OP(O)(ORh4)(ORi4), P(O)(ORh4)(ORi4), and BRj4Rk4. wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R4A substituents;

or, alternatively,

(b) when R2 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa2, SRa2, NHORa2, C(O)Rb2, C(O)NRc2Rd2,

C(O)NRc2(ORa2), C(O)ORa2, O C(O)Rb2, O C(O)NRc2Rd2, NRc2Rd2,

NRc2NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2,

C(=NRe2)Rb2, C(=NOH)Rb2, C(=NCN)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2)NRc2Rd2, NRc2C(=NOH)NRc2Rd2, NRc2C(=NCN)NRc2Rd2, NRc2C(=NRe2)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2,

NRc2S(O)(=NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, OS(O)(=NRe2)Rb2, OS(O)2Rb2, SF5, P(O)Rf2Rg2, OP(O)(ORh2)(ORi2), P(O)(ORh2)(ORi2), and BRj2Rk2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5- 10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)- C1-6 alkyl- of R2 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2A substituents;

then R4 is selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa4, SRa4, NHORa4, C(O)Rb4, C(O)NRc4Rd4,

C(O)NRc4(ORa4), C(O)ORa4, O C(O)Rb4, O C(O)NRc4Rd4, NRc4Rd4, NRc4NRc4Rd4, NRc4 C(O)Rb4, NRc4 C(O)ORa4, NRc4 C(O)NRc4Rd4,

C(=NRe4)Rb4, C(=NOH)Rb4, C(=NCN)Rb4, C(=NRe4)NRc4Rd4, NRc4C(=NRe4)NRc4Rd4, NRc4C(=NOH)NRc4Rd4, NRc4C(=NCN)NRc4Rd4, NRc4C(=NRe4)Rb4, NRc4S(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)(=NRe4)Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, OS(O)(=NRe4)Rb4, OS(O)2Rb4, SF5, P(O)Rf4Rg4, OP(O)(ORh4)(ORi4), P(O)(ORh4)(ORi4), and BRj4Rk4, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5- 10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)- C1-6 alkyl- of R4 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R4A substituents;

each Ra2, Rb2, Rc2, and Rd2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra2, Rb2, Rc2 and Rd2 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2A substituents;

or, any Rc2 and Rd2, attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocyclo alkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2A substituents;

each Re2 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf2 and Rg2 is independently selected fromH, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh2 and Ri2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj2 and Rk2 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj2 and Rk2 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

each R2A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb21, C(O)NRc21Rd21, C(O)NRc21(ORa21),

C(O)ORa21, O C(O)Rb21, O C(O)NRc21Rd21, NRc21Rd21, NRc21NRc21Rd21,

NRc21C(O)Rb21, NRc21C(O)ORa21, NRc21C(O)NRc21Rd21, C(=NRe21)Rb21, C(=NOH)Rb21, C(=NCN)Rb21, C(=NRe21)NRc21Rd21, NRc21C(=NRe21)NRc21Rd21, NRc21C(=NOH)NRc21Rd21, NRc21C(=NCN)NRc21Rd21, NRc21C(=NRe21)Rb21, NRc21S(O)NRc21Rd21, NRc21S(O)Rb21, NRc21S(O)2Rb21, NRc21S(O)(=NRe21)Rb21, NRc21S(O)2NRc21Rd21, S(O)Rb21, S(O)NRc21Rd21, S(O)2Rb21, S(O)2NRc21Rd21, OS(O)(=NRe21)Rb21, OS(O)2Rb21, SF5, P(O)Rf21Rg21, OP(O)(ORh21)(ORi21), P(O)(ORh21)(ORi21), and BRj21Rk21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R2A are each optionally substituted with 1, 2, 3, or 4 independently selected R2B substituents;

each Ra21, Rb21, Rc21 and Rd21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra21, Rb21, Rc21 and Rd21 are each optionally substituted with 1, 2, 3, or 4 independently selected R2B substituents;

or, any Rc21 and Rd21, atached to the same N atom, together with the N atom to which they are atached, form a 4-10 membered hetero cycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R2B substituents;

each Re21 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf21 and Rg21 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh21 and Ri21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj21 and Rk21 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj21 and Rk21 atached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

each R2B is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa22, SRa22, NHORa22, C(O)Rb22, C(O)NRc22Rd22, C(O)NRc22(ORa22),

C(O)ORa22, O C(O)Rb22, O C(O)NRc22Rd22, NRc22Rd22, NRc22NRc22Rd22,

NRc22 C(O)Rb22, NRc22 C(O)ORa22, NRc22 C(O)NRc22Rd22, C(=NRe22)Rb22, C(=NOH)Rb22, C(=NCN)Rb22, C(=NRe22)NRc22Rd22, NRc22C(=NRe22)NRc22Rd22, NRc22C(=NOH)NRc22Rd22, NRc22C(=NCN)NRc22Rd22, NRc22C(=NRe22)Rb22, NRc22S(O)NRc22Rd22, NRc22S(O)Rb22, NRc22S(O)2Rb22, NRc22S(O)(=NRe22)Rb22, NRc22S(O)2NRc22Rd22, S(O)Rb22, S(O)NRc22Rd22, S(O)2Rb22, S(O)2NRc22Rd22, OS(O)(=NRe22)Rb22, OS(O)2Rb22, SF5, P(O)Rf22Rg22, OP(O)(ORh22)(ORi22), P(O)(ORh22)(ORi22), and BRj22Rk22. wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R2B are each optionally substituted with 1, 2, 3, or 4 independently selected R2C substituents;

each Ra22, Rb22, Rc22 and Rd22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra22, Rb22, Rc22 and Rd22 are each optionally substituted with 1, 2, 3, or 4 independently selected R2C substituents;

or, any Rc22 and Rd22, attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R2C substituents;

each Re22 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf22 and Rg22 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh22 and Ri22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj22 and Rk22 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj22 and Rk22 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

each R2C is independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-C1-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 alkyl) carbamyl, carboxy, C1-3 alkylcarbonyl, C1-4 alkoxycarbonyl, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3

alkylcarbonyloxy, amino carbonyloxy, C1-3 alkylaminocarbonyloxy, di(C1-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino;

each Ra4, Rb4, Rc4, and Rd4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered hetero cycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra4, Rb4, Rc4 and Rd4 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R4A substituents;

or, any Rc4 and Rd4, attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R4A substituents;

each Re4 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf4 and Rg4 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh4 and Ri4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj4 and Rk4 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj4 and Rk4 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

each R4A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa41, SRa41, NHORa41, C(O)Rb41, C(O)NRc41Rd41, C(O)NRc41(ORa41),

C(O)ORa41, O C(O)Rb41, O C(O)NRc41Rd41, NRc41Rd41, NRc41NRc41Rd41, NRc41 C(O)Rb41, NRc41 C(O)ORa41, NRc41 C(O)NRc41Rd41, C(=NRe41)Rb41, C(=NOH)Rb41, C(=NCN)Rb41, C(=NRe41)NRc41Rd41, NRc41C(=NRe41)NRc41Rd41, NRc41C(=NOH)NRc41Rd41, NRc41C(=NCN)NRc41Rd41, NRc41C(=NRe41)Rb41, NRc41S(O)NRc41Rd41, NRc41S(O)Rb41, NRC41S(O)2Rm1, NRc41S(O)(=NRe41)Rb41, NRc41S(O)2NRc41Rd41, S(O)Rb41, S(O)NRc41Rd41, S(O)2Rb41, S(O)2NRc41Rd41, OS(O)(=NRe41)Rb41, OS(O)2Rb41, SF5, P(O)Rf41Rg41, OP(O)(ORh41)(ORi41), P(O)(ORh41)(ORi41), and BRj41Rk41, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4A are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R4B substituents;

each Ra41, Rb41, Rc41 and Rd41 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra41, Rb41, Rc41 and Rd41 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R4B substituents;

or, any Rc41 and Rd41, atached to the same N atom, together with the N atom to which they are atached, form a 4-10 membered hetero cycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R4B substituents;

each Re41 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf41 and Rg41 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh41 and Ri41 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj41 and Rk41 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj41 and Rk41 atached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

each R4B is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa42, SRa42, NHORa42, C(O)Rb42, C(O)NRc42Rd42, C(O)NRc42(ORa42),

C(O)ORa42, O C(O)Rb42, O C(O)NRc42Rd42, NRc42Rd42, NRc42NRc42Rd42,

NRc42 C(O)Rb42, NRc42 C(O)ORa42, NRc42 C(O)NRc42Rd42, C(=NRe42)Rb42, C(=NOH)Rb42, C(=NCN)Rb42, C(=NRe42)NRc42Rd42, NRc42C(=NRe42)NRc42Rd42, NRc42C(=NOH)NRc42Rd42, NRc42C(=NCN)NRc42Rd42, NRc42C(=NRe42)Rb42, NRc42S(O)NRc42Rd42, NRc42S(O)Rb42, NRc42S(O)2Rb42, NRc42S(O)(=NRe42)Rb42, NRc42S(O)2NRc42Rd42, S(O)Rb42, S(O)NRc42Rd42, S(O)2Rb42, S(O)2NRc42Rd42,

OS(O)(=NRe42)Rb42, OS(O)2Rb42, SF5, P(O)Rf42Rg42, OP(O)(ORh42)(ORi42), P(O)(ORh42)(ORi42), and BRj42Rk42. wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4B are each optionally substituted with 1, 2, 3, or 4 independently selected R4C substituents;

each Ra42, Rb42, Rc42 and Rd42 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra42, Rb42, Rc42 and Rd42 are each optionally substituted with 1, 2, 3, or 4 independently selected R4C substituents;

or, any Rc42 and Rd42, atached to the same N atom, together with the N atom to which they are atached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R4C substituents;

each Re42 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf42 and Rg42 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh42 and Ri42 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj42 and Rk42 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj42 and Rk42 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

each R4C is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-1 0 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa43, SRa43, NHORa43, C(O)Rb43, C(O)NRc43Rd43, C(O)NRc43(ORa43),

C(O)ORa43, O C(O)Rb43, O C(O)NRc43Rd43, NRc43Rd43, NRc43NRc43Rd43,

NRc43 C(O)Rb43, NRc43 C(O)ORa43, NRc43 C(O)NRc43Rd43, C(=NRe43)Rb43, C(=NOH)Rb43, C(=NCN)Rb43, C(=NRe43)NRc43Rd43, NRc43C(=NRe43)NRc43Rd43, NRc43C(=NOH)NRc43Rd43, NRc43C(=NCN)NRc43Rd43, NRc43C(=NRe43)Rb43, NRc43S(O)NRc43Rd43, NRc43S(O)Rb43, NRc43S(O)2Rb43, NRc43S(O)(=NRe43)Rb43, NRc43S(O)2NRc43Rd43, S(O)Rb43, S(O)NRc43Rd43, S(O)2Rb43, S(O)2NRc43Rd43, OS(O)(=NRe43)Rb43, OS(O)2Rb43, SF5, P(O)Rf43Rg43, OP(O)(ORh43)(ORi43), P(O)(ORh43)(ORi43), and BRj43Rk43. wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4C are each optionally substituted with 1, 2, 3, or 4 independently selected R4D substituents;

each Ra43, Rb43, Rc43 and Rd43 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra43, Rb43, Rc43 and Rd43 are each optionally substituted with 1, 2, 3, or 4 independently selected R4D substituents;

or, any Rc43 and Rd43, attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R4D substituents;

each Re43 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf43 and Rg43 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh43 and Ri43 is independently selected fromH, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj43 and Rk43 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj43 and Rk43 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

each R4D is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-7 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa44, SRa44, NHORa44, C(O)Rb44, C(O)NRc44Rd44, C(O)NRc44(ORa44),

C(O)ORa44, O C(O)Rb44, O C(O)NRc44Rd44, NRc44Rd44, NRc44NRc44Rd44, NRc44 C(O)Rb44, NRc44 C(O)ORa44, NRc44 C(O)NRc44Rd44, C(=NRe44)Rb44, C(=NOH)Rb44, C(=NCN)Rb44, C(=NRe44)NRc44Rd44, NRc44C(=NRe44)NRc44Rd44, NRc44C(=NOH)NRc44Rd44, NRc44C(=NCN)NRc44Rd44, NRc44C(=NRe44)Rb44,

NRc44S(O)NRc44Rd44, NRc44S(O)Rb44, NRc44S(O)2Rb44, NRc44S(O)(=NRe44)Rb44, NRc44S(O)2NRc44Rd44, S(O)Rb44, S(O)NRc44Rd44, S(O)2Rb44, S(O)2NRc44Rd44, OS(O)(=NRe44)Rb44, OS(O)2Rb44, SF5, P(O)Rf44Rg44, OP(O)(ORh44)(ORi44), P(O)(ORh44)(ORi44), and BRj44Rk44, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-7 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R4D are each optionally substituted with 1, 2, 3, or 4 independently selected R4E substituents;

each Ra44, Rb44, Rc44 and Rd44 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-7 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-7 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra44, Rb44, Rc44 and Rd44 are each optionally substituted with 1, 2, 3, or 4 independently selected R4E substituents;

or, any Rc44 and Rd44, attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group, wherein the 4-, 5-, 6-, or 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R4E substituents;

each Re44 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;

each Rf44 and Rg44 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-7 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-;

each Rh44 and Ri44 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-7 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-;

each Rj44 and Rk44 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

or any Rj44 and Rk44 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl; and

each R4E is independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-C1-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di( C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di( C1-3 alkyl) carbamyl, carboxy, C1-3 alkylcarbonyl, C1-4 alkoxycarbonyl, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylcarbonyloxy, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di( C1-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, amino sulfonyl, C1-3 alkylaminosulfonyl, di( C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di( C1-3 alkyl)aminosulfonylamino, aminocarbonylamino,

C1-3 alkylaminocarbonylamino, and di( C1-3 alkyl)aminocarbonylamino.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein 1, 2, 3, 4, 5, 6, 7, or 8 hydrogen atoms, attached to carbon atoms of any alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl substituents or -C1-6 alkyl-, alkylene, alkenylene, and alkynylene linking groups, are each optionally replaced by a deuterium atom.

3. The compound of claim 1 or 2, which is a compound of Formula (Ila):


or a pharmaceutically acceptable salt thereof.

4. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein R3 is CN or H.

5. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein R3 is H.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered hetero cycloalkyl, wherein the phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl of R2 are each optionally substituted with 1, 2, or 3 independently selected R2A substituents;

each R2A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb21,

C(O)NRc21Rd21, C(O)ORa21, O C(O)Rb21, O C(O)NRc21Rd21, NRc21Rd21, NRc21 C(O)Rb21, NRc21 C(O)ORa21, NRc21 C(O)NRc21Rd21, S(O)Rb21, and S(O)2Rb21, wherein said phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl of R2A are optionally substituted with 1, 2, or 3 independently selected R2B substitutents;

each Ra21, Rb21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

each R2B is independently selected from halo, OH, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkyl, C1-4 haloalkyl, amino, C1-3 alkylamino, and di( C1-3 alkyl)amino.

7. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-6 membered hetero cycloalkyl, wherein the C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-6 membered heterocycloalkyl of R2 are each optionally substituted with 1 or 2 independently selected R2A substituents;

each R2A is independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, and

C(O)NRc21Rd21, wherein said C1-4 alkyl of R2A is optionally substituted with 1, 2, or 3 independently selected R2B substitutents;

each Ra21, Rb21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

each R2B is independently selected from halo and OH.

8. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from cyclopropyl, oxazolyl, triazolyl, pyrazolyl, pyridyl, pyrimidinyl, dihydropyridin-(2H)-yl, and pyridinonyl, each of which is optionally substituted with 1 or 2 independently selected R2A substituents;

each R2A is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb21, C(O)NRc21Rd21,

C(O)ORa21, O C(O)Rb21, O C(O)NRc21Rd21, NRc21Rd21, NRc21 C(O)Rb21, NRc21 C(O)ORa21, NRc21 C(O)NRc21Rd21, and S(O)Rb21, wherein said C1-6 alkyl of R2A is optionally substituted with 1, 2, or 3 independently selected R2B substituents;

each Ra21, Rb21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, C1- 6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; and

each R2B is independently selected from halo and OH.

9. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from 1-(trifluoromethyl)cycloprop-1-yl, 1-ethyl- 1H-pyrazol-5-yl, 1-propyl-1H-pyrazol-5-yl, 1-methyl-6-oxo-1,6-dihydropyridin-3-yl, pyrimidin-4-yl, 3,6-dihydropyridin-4-yl-1(2H)-carboxamide, pyridin-4-yl, 4-(1-hydroxyethyl)-2-methyloxazol-5-yl, 2,2-difluoro-1-hydroxyethyl)-2-methyloxazol-5-yl, 1-ethyl-1H-1,2,3-triazol-5-yl, and 1-methyl-1H-1,2,3-triazol-5-yl.

10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa4, SRa4, NHORa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, O C(O)Rb4, O C(O)NRc4Rd4, NRc4Rd4, NRc4 C(O)Rb4, NRc4 C(O)ORa4, NRc4 C(O)NRc4Rd4, S(O)Rb4, and S(O)2Rb4, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4 are each optionally substituted with 1, 2, 3, or 4 independently selected R4A substituents;

each Ra4, Rb4, Rc4, and Rd4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein said C1-6 alkyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl of Ra4, Rb4, Rc4, and Rd4 are each optionally substituted by 1, 2, or 3 independently selected R4A substituents;

each R4A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa41, SRa41, NHORa41, C(O)Rb41,

C(O)NRc41Rd41, C(O)ORa41, O C(O)Rb41, O C(O)NRc41Rd41, NRc41Rd41, NRc41 C(O)Rb41, NRc41 C(O)ORa41, NRc41 C(O)NRc41Rd41, S(O)Rb41, and S(O)2Rb41, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl of R4A are each optionally substituted by 1 or 2 independently selected R4B substituents;

each Ra41, Rb41, Rc41, and Rd41 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl, wherein said C1-6 alkyl of Ra41, Rb41, Rc41, and Rd41 is optionally substituted by 1, 2, or 3 independently selected R4B substituents; and

each R4B is independently selected from halo, OH, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkyl, C1-4 haloalkyl, amino, C1-3 alkylamino, and di( C1-3 alkyl)amino.

11. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-3 alkyl-, (5-10 membered heteroaryl)-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl-, C(O)Rb4, C(O)NRc4Rd4, and NRc4Rd4, wherein the phenyl, 5-6 membered heteroaryl, 4-7 membered heterocyclo alkyl, phenyl-C1-3 alkyl-, (5-10 membered heteroaryl)-C1-3 alkyl-, and (4-7 membered heterocycloalkyl)-C1-3 alkyl- of R4 are each optionally substituted with 1 or 2 independently selected R4A substituents;

each Ra4, Rb4, Rc4, and Rd4 is independently selected from H, C1-6 alkyl, phenyl, and 4-7 membered heterocycloalkyl, wherein said C1-6 alkyl, phenyl, and 4-7 membered heterocycloalkyl of Ra4, Rb4, Rc4, and Rd4 are optionally substituted with 1, 2, or 3 independently selected R4A substituents;

each R4A is independently selected from halo, 4-7 membered heterocycloalkyl, and OH, wherein said 4-7 membered heterocycloalkyl of R4A is optionally substituted with 1 or 2 independently selected R4B substituents; and

each R4B is independently selected from halo, OH, and C1-4 alkyl.

12. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from C(O)NHC1-6alkyl, C(O)-azetidinyl, C(O)-pyrrolidinyl, C(O)-piperidinyl, C(O)N(CI-6 alkyl)2, NH C(O)OC1-6 alkyl, (azetidinyl)-C1-6 alkyl, (pyridyl)-C1-6 alkyl, (phenyl)-C1-6 alkyl, (fluorophenyl)-C1-6 alkyl, 3,6-dihydro-2H-pyranyl, NH-(phenyl), pyridyl, and (pyrrolo[3,2-b]pyridinyl)-C1-6 alkyl, wherein each C1-6 alkyl and azetidinyl group is optionally substituted by 1 or 2 OH groups; and each pyridyl is optionally substituted by a methylpiperazinyl group.

13. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from C(O)NHCH2CH3, C(O)N(CH3)(CH2CH3),

C(O)N(CH2CH3)2, NH C(O)OCH2CH3, C(O)-azetidinyl, C(O)-hydroxyazetidinyl,

C(O)-pyrrolidinyl, C(O)-piperidinyl, CH2-azetidinyl, CH2-pyridyl, CH2-fluorophenyl, CH(OH)-flurophenyl, NH-phenyl, 3,6-dihydro-2H-pyranyl, (methylpiperazinyl)pyridinyl, and (1H-pyrrolo[3,2-b]pyridin-3-yl)methyl.

14. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, and CN.

15. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, difluoroethyl, bromo, and CN.

16. The compound of any one of claims 14 and 15, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from phenyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and C(O)NRc4Rd4, wherein the phenyl-C1-6 alkyl- and (5-6 membered heteroaryl)-C1-6 alkyl- of R4 are each optionally substituted with 1 or 2 substituents independently selected from OH and halo; and

each Ra4, Rc4, and Rd4 is independently selected from H and C1-6 alkyl.

17. The compound of any one of claims 14 and 15, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from -C(O)NHCH2CH3, -CH2-pyridyl, CH2-fluorophenyl, and CH(OH)-fluorophenyl.

18. The compound of claim 3, or a pharmaceutically acceptable salt thereof, wherein:

R3 is H or CN;

Cy1 is phenyl which is substituted by 1 or 2 independently selected R7 substituents;

each R7 is independently selected from halo and CN;

R2 is selected from phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl, wherein the phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered hetero cycloalkyl of R2 are each optionally substituted with 1, 2, or 3 independently selected R2A substituents;

each R2A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb21,

C(O)NRc21Rd21, C(O)ORa21, O C(O)Rb21, O C(O)NRc21Rd21, NRc21Rd21, NRc21 C(O)Rb21, NRc21 C(O)ORa21, NRc21C(O)NRc21Rd21, S(O)Rb21, and S(O)2Rb21, wherein said phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl of R2A are optionally substituted with 1, 2, or 3 independently selected R2B substitutents;

each Ra21, Rb21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

each R2B is independently selected from halo, OH, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkyl, C1-4 haloalkyl, amino, C1-3 alkylamino, and di( C1-3 alkyl)amino;

R4 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa4, SRa4, NHORa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, O C(O)Rb4, O C(O)NRc4Rd4, NRc4Rd4, NRc4 C(O)Rb4, NRc4 C(O)ORa4, NRc4 C(O)NRc4Rd4, S(O)Rb4, and S(O)2Rb4, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4 are each optionally substituted with 1, 2, 3, or 4 independently selected R4A substituents;

each Ra4, Rb4, Rc4, and Rd4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein said C1-6 alkyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl of Ra4, Rb4, Rc4, and Rd4 are each optionally substituted by 1, 2, or 3 independently selected R4A substituents;

each R4A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa41, SRa41, NHORa41, C(O)Rb41,

C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41 C(O)ORa41, NRc41 C (O)NRc41 Rd41 , S(O)Rb41, and S(O)2Rb41, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl of R4A are each optionally substituted by 1 or 2 independently selected R4B substituents;

each Ra41, Rb41, Rc41, and Rd41 is independently selected from H, C1-6 alkyl, and C1-6haloalkyl, wherein said C1-6 alkyl of Ra41, Rb41, Rc41, and Rd41 is optionally substituted by 1, 2, or 3 independently selected R4B substituents; and

each R4B is independently selected from halo, OH, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkyl, C1-4 haloalkyl, amino, C1-3 alkylamino, and di(C1-3 alkyl)amino,

19. The compound of claim 3, or a pharmaceutically acceptable salt thereof, wherein:

R3 is H or CN;

Cy1 is 3-cyanophenyl or 3-cyano-2-fluorophenyl;

R2 is selected from C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-6 membered heterocycloalkyl, wherein the C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-6 membered heterocycloalkyl of R2 are each optionally substituted with 1 or 2 independently selected R2A substituents;

each R2A is independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, and

C(O)NRc21Rd21, wherein said C1-4 alkyl of R2A is optionally substituted with 1, 2, or 3 independently selected R2B substitutents;

each Ra21, Rb21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

each R2B is independently selected from halo and OH;

R4 is selected from phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-3 alkyl-, (5-10 membered heteroaryl)-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl-, C(O)Rb4, C(O)NRc4Rd4, and NRc4Rd4, wherein the phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-3 alkyl-, (5-10 membered heteroaryl)-C1-3 alkyl-, and (4-7 membered

heterocycloalkyl)-C1-3 alkyl- of R4 are each optionally substituted with 1 or 2 independently selected R4A substituents;

each Ra4, Rb4, Rc4, and Rd4 is independently selected from H, C1-6 alkyl, phenyl, and 4-7 membered heterocycloalkyl, wherein said C1-6 alkyl, phenyl, and 4-7 membered heterocycloalkyl of Ra4, Rb4, Rc4, and Rd4 are optionally substituted with 1, 2, or 3 independently selected R4A substituents;

each R4A is independently selected from halo, 4-7 membered heterocycloalkyl, and OH, wherein said 4-7 membered heterocycloalkyl of R4A is optionally substituted with 1 or 2 independently selected R4B substituents; and

each R4B is independently selected from halo, OH, and C1-4 alkyl.

20. The compound of claim 3, or a pharmaceutically acceptable salt thereof, wherein:

R3 is H or CN;

Cy1 is phenyl which is substituted by 1 or 2 independently selected R7 substituents;

each R7 is independently selected from halo and CN;

R2 is selected from H, halo, C1-6 alkyl, C1-6 haloalkyl, and CN;

R4 is selected from phenyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and C(O)NRc4Rd4, wherein the phenyl-C1-6 alkyl- and (5-6 membered heteroaryl)-C1-6 alkyl- of R4 are each optionally substituted with 1 or 2 substituents independently selected from OH and halo; and

each Ra4, Rc4, and Rd4 is independently selected from H and C1-6 alkyl.

21. The compound of any one of claims 1 to 3, which is a compound of Formula (IIb):


or a pharmaceutically acceptable salt thereof, wherein n is an integer from 0 to 4.

22. The compound of any one of claims 1 to 3, which is a compound of Formula

(IIc):


or a pharmaceutically acceptable salt thereof.

23. The compound of claim 1 or 2, which is a compound of Formula (IIIa):


or a pharmaceutically acceptable salt thereof.

24. The compound of any one of claims 1 to 17 and 23, or a pharmaceutically acceptable salt thereof, wherein Cy1 is phenyl which is substituted by 1 or 2 independently selected R7 substituents; and

each R7 is independently selected from halo and CN.

25. The compound of any one of claims 1 to 17 and 23, or a pharmaceutically acceptable salt thereof, wherein Cy1 is cyanophenyl.

26. The compound of any one of claims 1 to 17 and 23, or a pharmaceutically acceptable salt thereof, wherein Cy1 is 3-cyanophenyl or 3-cyano-2-fluorophenyl.

27. The compound of any one of claims 1, 2, and 23-26, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocyclo alkyl, wherein the C6-10 aryl, C3- 10 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl of R2 are each optionally substituted with 1, 2, 3, or 4 independently selected R2A substituents;

each R2A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, ORa21, SR321, NHORa21, C(O)Rb21,

C(O)NRc21Rd21, C(O)ORa21, O C(O)Rb21, O C(O)NRc21Rd21, NRc21Rd21, NRc21 C(O)Rb21, NRc21 C(O)ORa21, NRc21 C(O)NRc21Rd21, S(O)Rb21, and S(O)2Rb21, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of R2A are each optionally substituted by 1, 2, or 3 independently selected R2B substitutents;

each Ra21, R241, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl, wherein said C1-6 alkyl of Ra21, R241, Rc21, and Rd21 is optionally substituted by 1, 2, or 3 independently selected R2A substituents; and

each R2B is independently selected from D, halo, OH, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkyl, C1-4 haloalkyl, amino, C1-3 alkylamino, and di( C1-3

alkyl)amino.

28. The compound of any one of claims 1, 2, and 23-26, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl, wherein the 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl of R2 are each optionally substituted with 1, 2, or 3 independently selected R2A substituents;

each R2A is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, and OH, wherein said C1-6 alkyl of R2A is optionally substituted by 1, 2, or 3 independently selected R2B substitutents; and

each R2B is independently selected from D, halo, and OH.

29. The compound of any one of claims 1, 2, and 23-26, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from 6-oxo-1,6-dihydropyridin-3-yl, pyrimidin-4-yl, 1-methyl-6-oxo-1,6-dihydropyridin-3-yl, 1-methyl-6-oxo-1,6-dihydropyridazin-3-yl, 4-methyloxazol-5-yl, 4-ethyloxazol-5-yl, 3-methylpyridin-4-yl, 4-(2,2-difluoro-1-hydroxyethyl)-2-methyloxazol-5-yl, 2-methyl-4-(2,2,2-trifluoro-1-hydroxyethyl)oxazol-5-yl, 1-ethyl-1H-pyrazol-5-yl, 6-hydroxypyridin-3-yl, 2,6-dimethylpyridin-4-yl, 3-methyl-1H-pyrazol-4-yl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, oxazol-5-yl, imidazo[1,2-a]pyridine-6-yl, 3-fluoropyridin-4-yl, and 1-(methyl-d3)-6-oxo-1,6-dihydropyridazin-3-yl.

30. The compound of any one of claims 1, 2, and 23-26, or a pharmaceutically acceptable salt thereof, wherein R2 is H.

31. The compound of any one of claims 1, 2, and 23 to 26, or a pharmaceutically acceptable salt thereof, wherein R2 is 6-oxo-1,6-dihydropyridin-3-yl or imidazo[1,2-a]pyridin-6-yl; and R4 is H.

32. The compound of any one of claims 1 , 2, and 23 to 26, or a pharmaceutically acceptable salt thereof, wherein R2 is H; and R4 is -NH C(O)OC1-6 alkyl.

33. The compound of any one of claims 1, 2, and 23-30, or a pharmaceutically acceptable salt thereof, wherein:

R4 is selected from C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-,

ORa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, NRc4Rd4, S(O)2NRc4Rd4, and S(O)2Rb4, wherein the C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4 are each optionally substituted with 1, 2, or 3 independently selected R4A substituents; each Ra4, Rb4, Rc4, and Rd4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra4, Rb4, Rc4 and Rd4 are each optionally substituted with 1, 2, or 3 independently selected R4A substituents;

each R4A is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered hetero aryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, ORa41, C(O)Rb41,

C(O)NRc41Rd41, C(O)ORa41, NRc41Rd41, S(O)2NRc41Rd41, and S(O)2Rb41, wherein the C1-6 alkyl, 5 C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4A are each optionally substituted with 1, 2, or 3 independently selected R4B substituents; each Ra41, Rb41, Rc41 and Rd41 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of Ra41, Rb41, Rc41 and Rd41 are each optionally substituted with 1, 2, or 3 independently selected R4B substituents;

each R4B is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C1-3 alkyl-, (C3-6 cycloalkyl)-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl-, (5-6 membered heteroaryl)-C1-3 alkyl-, CN, ORa42, C(O)Rb42, C(O)NRc42Rd42,

C(O)ORa42, NRc42Rd42, S(O)2NRc42Rd42, and S(O)2Rb42, wherein the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C1- 3 alkyl-, (C3-6 cycloalkyl)-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl-, (5-6 membered heteroaryl)-C1-3 alkyl- of R4B are each optionally substituted with 1, 2, or 3 independently selected R4C substituents;

each Ra42, Rb42, Rc42 and Rd42 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of Ra42, Rb42, Rc42 and Rd42 are each optionally substituted with 1, 2, or 3 independently selected R4C substituents;

each R4C is independently selected from C1-6 alkyl, C1-6 haloalkyl, CN, ORa43,

C(O)Rb43, C(O)NRc43Rd43, C(O)ORa43, NRc43Rd43, S(O)2NRc43Rd43, and S(O)2Rb43, wherein the C1-6 alkyl of R4C is optionally substituted with 1 or 2 independently selected R4D substituents;

each Ra43, Rb43, Rc43 and Rd43 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl, wherein the C1-6 alkyl of Ra43, Rb43, Rc43 and Rd43 are each optionally substituted with 1 or 2 independently selected R4D substituents;

or, any Rc43 and Rd43, attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, or 6-membered heterocycloalkyl group, wherein the 4-, 5-, or 6-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R4D substituents; and

each R4D is independently selected from C1-3 alkyl and OH.

34. The compound of any one of claims 1, 2, and 23 to 30, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from phenyl-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl-, (5-10 membered heteroaryl)-C1-3 alkyl-, ORa4, C(O)Rb4, and S(O)2Rb4, wherein the phenyl-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl- and (5-10 membered heteroaryl)-C1-3 alkyl- of R4 are each optionally substituted with 1, 2, or 3 independently selected R4A substituents;

each Ra4, Rb4, Rc4, and Rd4 is independently selected from phenyl, 4-7 membered heterocycloalkyl, and (5-6 membered heteroaryl)-C1-3 alkyl-, wherein the

phenyl, 4-7 membered heterocycloalkyl, and (5-6 membered heteroaryl)-C1-3 alkyl- of Ra4, Rb4, Rc4 and Rd4 are each optionally substituted with 1, 2, or 3 independently selected R4A substituents;

each R4A is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, 5-6 membered heteroaryl, (4-10 membered heterocycloalkyl)-C1-3 alkyl-, ORa41, S(O)2Rb41, and NRc41Rd41, wherein the C1-6 alkyl, 5-6 membered heteroaryl, and (4-10 membered heterocycloalkyl)-C1-3 alkyl- of R4A are each optionally substituted with 1, 2, or 3 independently selected R4B substituents;

each Ra41, Rb41, Rc41 and Rd41 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, and 5-6 membered heteroaryl, wherein the C1-6 alkyl and 5-6 membered heteroaryl of Ra41, Rb41, Rc41 and Rd41 are each optionally substituted with 1, 2, or 3 independently selected R4B substituents;

each R4B is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 4-7 membered hetero cycloalkyl, (5-6 membered heteroaryl)-C1-3 alkyl-, CN, ORa42, C(O)Rb42, C(O)ORa42, and NRc42Rd42, wherein the C1-6 alkyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, and (5-6 membered heteroaryl)-C1-3 alkyl- of R4B are each optionally substituted with 1, 2, or 3 independently selected R4C substituents;

each Ra42, Rb42, Rc42 and Rd42 is independently selected from H, C1-6 alkyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 5-7 membered heterocycloalkyl, wherein the C1-6 alkyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 5-7 membered heterocycloalkyl of Ra42, Rb42, Rc42 and Rd42 are each optionally substituted with 1, 2, or 3 independently selected R4C substituents;

each R4C is independently selected from C1-6 alkyl, CN, C(O)NRc43Rd43,

C(O)ORa43, NRc43Rd43, and S(O)2Rb43, wherein the C1-6 alkyl of R4C is optionally substituted with 1 or 2 independently selected R4D substituents;

each Ra43, Rb43, Rc43 and Rd43 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl, wherein the C1-6 alkyl of Ra43, Rb43, Rc43 and Rd43 are each optionally substituted with 1 or 2 independently selected R4D substituents;

or, any Rc43 and Rd43, attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, or 6-membered heterocycloalkyl group,

wherein the 4-, 5-, or 6-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R4D substituents;

each R4D is independently selected from C1-3 alkyl and OH.

35. The compound of any one of claims 1, 2, and 23-30, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from pyridin-2-ylmethyl, 1H-Pyrrolo[2,3-b]pyridin-1-yl, 7H-pyrrolo[2,3-b]pyridin-7-yl, 2-fluorophenoxy, hydroxy(pyridin-2-yl)methyl, 2-(1-methyl-1H-pyrazol-4-yl)benzyl, (imidazo[1,2-a]pyridin-8-yl)methyl, (pyrazolo[1,5-a]pyridin-7-yl)methyl, (2H-indazol-2-yl)methyl, (1H-indazol-1-yl)methyl, (2,6-difluorophenyl)(hydroxy)methyl, (2,5-difluorophenyl)(hydroxy)methyl, (2,3-difluorophenyl)(hydroxy)methyl, (2-fluorophenyl)(hydroxy)methyl, (2-chlorophenyl)(hydroxy)methyl, hydroxy(phenyl)methyl, phenylsulfonyl, azetidine-1-carbonyl, benzo[d]oxazol-4-ylmethyl, 2-fluoro-6-(1-methyl-1H-pyrazol-5-yl)benzyl, 2-fluoro-6-((6-methyl-5-oxo-2,6-diazaspiro[3.4]octan-2-yl)methyl)benzyl, 2-fluoro-6-((6-oxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)methyl)benzyl, 2-fluoro-6-(((2-oxopyrrolidin-3-yl)amino)methyl)benzyl, 2-fluoro-6-((3-oxopiperazin-1-yl)methyl)benzyl, 2-fluoro-6-(((1-methyl-2-oxopyrrolidin-3-yl)amino)methyl)benzyl, 2-fhioro-6-(((2-methyl-2H-1,2,3-triazol-4-yl)amino)methyl)benzyl, 2-(((2-oxopyrrolidin-3-yl)amino)methyl)benzyl, amino(2,6-difluorophenyl)methyl, (2,6-difluorophenyl)(methylamino)methyl, (2,6-difluorophenyl)((2-hydroxyethyl)amino)methyl, amino(2-fluorophenyl)methyl, amino(2,6-difluorophenyl)methyl, (3-(oxazol-5-yl)pyridin-2-yl)methyl, 2-fluoro-6-(1-methyl-1H-pyrazol-4-yl)benzyl, (1-((1-methyl-1H-imidazol-4-yl)sulfonyl)pyrrolidin-2-yl)methyl, 2-((1-acetylpiperidin-4-yl)methyl)-6-fluorobenzyl, (2-(difluoromethoxy)-6-fluorophenyl)(hydroxy)methyl, 2-fluoro-6-(1-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrazol-4-yl)benzyl, (2-((dimethylamino)methyl)-6-fluorophenyl)(hydroxy)methyl, 2-fluoro-6-(1-(pyridin-2-ylmethyl)-1H-pyrazol-4-yl)benzyl, (2-fluoro-6-(pyrrolidin-1-ylmethyl)phenyl)(hydroxy)methyl, 2-fluoro-6-(1-(2-(methylsulfonyl)ethyl)-1H-pyrazol-4-yl)benzyl, 2-fluoro-6-((6-oxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)methyl)phenyl)(hydroxy)methyl, 2-fluoro-6-(1-((trans)-3-(methylamino)cyclobutyl)-1H-pyrazol-4-yl)benzyl, 2-(1-(2- cyanoethyl)-1H-pyrazol-4-yl)-6-fluorobenzyl, 2-fluoro-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)-1H-pyrazol-4-yl)benzyl, (3-methylpyridin-2-yl)methoxy, (3-((1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl)amino)pyridin-2-yl)methyl, (3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)pyridin-2-yl)methyl, (3-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl, 2-((3-hydroxypyrrolidin-1-yl)methyl)benzyl, and (6-methoxypyridin-2-yl)methyl.

36. The compound of claim 23, or a pharmaceutically acceptable salt thereof, wherein:

Cy1 is phenyl which is substituted by 1 or 2 independently selected R7 substituents;

each R7 is independently selected from halo and CN;

R2 is selected from H, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of R2 are each optionally substituted with 1, 2, 3, or 4 independently selected R2A substituents;

each R2A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2- 6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb21,

C(O)NRc21Rd21, C(O)ORa21, O C(O)Rb21, O C(O)NRc21Rd21, NRc21Rd21, NRc21 C(O)Rb21, NRc21 C(O)ORa21, NRc21C(O)NRc21Rd21, S(O)Rb21, and S(O)2Rb21, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of R2A are each optionally substituted by 1, 2, or 3 independently selected R2B substitutents;

each Ra21, R241, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl, wherein said C1-6 alkyl of Ra21, R241, Rc21, and Rd21 is optionally substituted by 1, 2, or 3 independently selected R2A substituents;

each R2B is independently selected from D, halo, OH, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkyl, C1-4 haloalkyl, amino, C1-3 alkylamino, and di(C1-3 alkyl)amino;

R4 is selected from C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-,

ORa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, NRc4Rd4, S(O)2NRc4Rd4, and S(O)2Rb4, wherein the C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4 are each optionally substituted with 1, 2, or 3 independently selected R4A substituents; each Ra4, Rb4, Rc4, and Rd4 is independently selected fromH, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra4, Rb4, Rc4 and Rd4 are each optionally substituted with 1, 2, or 3 independently selected R4A substituents;

each R4A is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, ORa41, C(O)Rb41,

C(O)NRc41Rd41, C(O)ORa41, NRc41Rd41, S(O)2NRc41Rd41, and S(O)2Rb41, wherein the C1-6 alkyl, 5 C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4A are each optionally substituted with 1, 2, or 3 independently selected R4B substituents; each Ra41, Rb41, Rc41 and Rd41 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of Ra41, Rb41, Rc41 and Rd41 are each optionally substituted with 1, 2, or 3 independently selected R4B substituents;

each R4B is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C1-3 alkyl-, (C3-6 cycloalkyl)-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl-, (5-6 membered heteroaryl)-C1-3 alkyl-, CN, ORa42, C(O)Rb42, C(O)NRc42Rd42,

C(O)ORa42, NRc42Rd42, S(O)2NRc42Rd42, and S(O)2Rb42, wherein the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C1- 3 alkyl-, (C3-6 cycloalkyl)-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl-, (5-6 membered heteroaryl)-C1-3 alkyl- of R4B are each optionally substituted with 1, 2, or 3 independently selected R4C substituents;

each Ra42, Rb42, Rc42 and Rd42 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of Ra42, Rb42, Rc42 and Rd42 are each optionally substituted with 1, 2, or 3 independently selected R4C substituents;

each R4C is independently selected from C1-6 alkyl, C1-6 haloalkyl, CN, ORa43,

C(O)Rb43, C(O)NRc43Rd43, C(O)ORa43, NRc43Rd43, S(O)2NRc43Rd43, and S(O)2Rb43, wherein the C1-6 alkyl, 4-7 membered heterocycloalkyl, and (5-6 membered heteroaryl)-C1-3 alkyl- of R4C are each optionally substituted with 1 or 2 independently selected R4D substituents;

each Ra43, Rb43, Rc43 and Rd43 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl, wherein the C1-6 alkyl of Ra43, Rb43, Rc43 and Rd43 are each optionally substituted with 1 or 2 independently selected R4D substituents;

or, any Rc43 and Rd43, attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, or 6-membered heterocycloalkyl group, wherein the 4-, 5-, or 6-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R4D substituents; and

each R4D is independently selected from C1-3 alkyl and OH.

37. The compound of claim 23, or a pharmaceutically acceptable salt thereof, wherein:

Cy1 is 3-cyanophenyl or 3-cyano-2-fluorophenyl;

R2 is selected from H, 5-10 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein the 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl of R2 are each optionally substituted with 1, 2, or 3 independently selected R2A substituents;

each R2A is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, and OH, wherein said C1-6 alkyl of R2A is optionally substituted by 1, 2, or 3 independently selected R2B substitutents;

each R2B is independently selected from D, halo, and OH;

R4 is selected from phenyl-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl-, (5-10 membered heteroaryl)-C1-3 alkyl-, ORa4, C(O)Rb4, and S(O)2Rb4, wherein the phenyl-C1-3 alkyl-, (4-7 membered heterocycloalkyl)-C1-3 alkyl- and (5-10 membered heteroaryl)-C1-3 alkyl- of R4 are each optionally substituted with 1, 2, or 3 independently selected R4A substituents;

each Ra4, Rb4, Rc4, and Rd4 is independently selected from phenyl, 4-7 membered heterocycloalkyl, and (5-6 membered heteroaryl)-C1-3 alkyl-, wherein the phenyl, 4-7 membered heterocycloalkyl, and (5-6 membered heteroaryl)-C1-3 alkyl- of Ra4, Rb4, Rc4 and Rd4 are each optionally substituted with 1, 2, or 3 independently selected R4A substituents;

each R4A is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, 5-6 membered heteroaryl, (4-10 membered heterocycloalkyl)-C1-3 alkyl-, ORa41, S(O)2Rb41, and NRc41Rd41, wherein the C1-6 alkyl, 5-6 membered heteroaryl, and (4-10 membered heterocycloalkyl)-C1-3 alkyl- of R4A are each optionally substituted with 1, 2, or 3 independently selected R4B substituents;

each Ra41, Rb41, Rc41 and Rd41 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, and 5-6 membered heteroaryl, wherein the C1-6 alkyl and 5-6 membered heteroaryl of Ra41, Rb41, Rc41 and Rd41 are each optionally substituted with 1, 2, or 3 independently selected R4B substituents;

each R4B is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 4-7 membered heterocycloalkyl, (5-6 membered heteroaryl)-C1-3 alkyl-, CN, ORa42, C(O)Rb42, C(O)ORa42, and NRc42Rd42, wherein the C1-6 alkyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, and (5-6 membered heteroaryl)-C1-3 alkyl- of R4B are each optionally substituted with 1, 2, or 3 independently selected R4C substituents;

each Ra42, Rb42, Rc42 and Rd42 is independently selected from H, C1-6 alkyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 5-7 membered heterocycloalkyl, wherein the C1-6 alkyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 5-7 membered

heterocycloalkyl of Ra42, Rb42, Rc42 and Rd42 are each optionally substituted with 1, 2, or 3 independently selected R4C substituents;

each R4C is independently selected from C1-6 alkyl, CN, C(O)NRc43Rd43,

C(O)ORa43, NRc43Rd43, and S(O)2Rb43, wherein the C1-6 alkyl, 4-7 membered heterocycloalkyl, and (5-6 membered heteroaryl)-C1-3 alkyl- of R4C are each optionally substituted with 1 or 2 independently selected R4D substituents;

each Ra43, Rb43, Rc43 and Rd43 is independently selected from H, C1-6 alkyl, and C1-6haloalkyl, wherein the C1-6 alkyl of Ra43, Rb43, Rc43 and Rd43 are each optionally substituted with 1 or 2 independently selected R4D substituents;

or, any Rc43 and Rd43, attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, or 6-membered heterocycloalkyl group, wherein the 4-, 5-, or 6-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R4D substituents; and

each R4D is independently selected from C1-3 alkyl and OH.

38. The compound of any one of claims 1, 2, and 23, or a pharmaceutically acceptable salt thereof, wherein:

R2 is selected from 5-6 membered heteroaryl and 4-6 membered heterocycloalkyl, wherein the 5-6 membered heteroaryl and 4-6 membered heterocyclo alkyl are each optionally substituted with 1 or 2 C1-3 alkyl groups;

R4 is phenyl-C1-3 alkyl- or pyridyl-C1-3 alkyl-, wherein the phenyl-C1-3 alkyl-and pyridyl-C1-3 alkyl- are each optionally substituted with 1, 2, or 3 substituents independently selected from OH and halo; and

Cy1 is cyanophenyl.

39. The compound of any one of claims 1, 2, and 23, which is a compound of

Formula (Illb):


or a pharmaceutically acceptable salt thereof, wherein n is an integer from 0 to 4.

40. The compound of any one of claims 1, 2, and 23, which is a compound of Formula (IIIc):


or a pharmaceutically acceptable salt thereof.

41. The compound of claim 1 or 2, selected from:

4-Amino-6-(3-cyanophenyl)-N-ethyl-7-(1-ethyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrazine-2-carboxamide;

4-Amino-6-(3-cyanophenyl)-N-ethyl-7-(1-propyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrazine-2-carboxamide;

4-Amino-6-(3-cyanophenyl)-N-ethyl-7-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyrazolo[1,5-a]pyrazine-2-carboxamide;

4-Amino-6-(3-cyanophenyl)-N-ethyl-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazine-2-carboxamide;

4-Amino-6-(3-cyanophenyl)-7-(l,1-difluoroethyl)-N-ethylpyrazolo[1,5-a]pyrazine-2-carboxamide;

4-Amino-6-(3-cyanophenyl)-N-ethyl-7-(1-(trifluoromethyl)cyclopropyl)pyrazolo[1,5-a]pyrazine-2-carboxamide;

3-(4-Amino-2-(azetidine-1-carbonyl)-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-7-(pyrimidin-4-yl)-2-(pyrrolidine-1-carbonyl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-2-(piperidine-1-carbonyl)-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

4-Amino-6-(3-cyanophenyl)-N,N-diethyl-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazine-2-carboxamide;

4-Amino-6-(3-cyanophenyl)-N-ethyl-N-methyl-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazine-2-carboxamide;

3-(4-Amino-2-(3-hydroxyazetidine-1-carbonyl)-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-2-(azetidin-1-ylmethyl)-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

Ethyl (8-amino-6-(3-cyanophenyl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)carbamate;

3-(8-Amino-5-(6-oxo-1,6-dihydropyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin- 6-yl)benzonitrile;

3-(4-Amino-2-(pyridin-2-ylmethyl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-2-(pyridin-2-ylmethyl)-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin- 6-yl)benzonitrile;

3-(4-Amino-7-(1-ethyl-1H-pyrazol-5-yl)-2-(pyridin-2-ylmethyl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

4-(4-Amino-6-(3-cyanophenyl)-2-(2-fluorobenzyl)pyrazolo[1,5-a]pyrazin-7-yl)-5,6-dihydropyridine-1(2H)-carboxamide;

4-Amino-6-(3-cyanophenyl)-2-(2-fluorobenzyl)pyrazolo[1,5-a]pyrazine-7-carbonitrile;

4-Amino-6-(3-cyanophenyl)-2-(2-fluorobenzyl)pyrazolo[1,5-a]pyrazine-3-carbonitrile;

3-(4-Amino-7-bromo-2-((2-fluorophenyl)(hydroxy)methyl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-2-((2-fluorophenyl)(hydroxy)methyl)-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-2-(3,6-dihydro-2H-pyran-4-yl)-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-2-(phenylamino)-7-(pyridin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-2-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-7-(pyridin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(pyridin-2-ylmethyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-5-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

(5)-1-(2-((8-Amino-6-(3-cyanophenyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorobenzyl)pyrrolidine-3-carboxylic acid;

1-(2-((8-Amino-6-(3-cyanophenyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorobenzyl)azetidine-3-carboxylic acid;

3-(2-((1H-Pyrrolo[2,3-b]pyridin-1-yl)methyl)-8-amino-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(2-((7H-pyrrolo[2,3-b]pyridin-7-yl)methyl)-8-amino-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-7-(4-(1-hydroxyethyl)-2-methyloxazol-5-yl)-2-(pyridin-2-ylmethyl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-7-(4-(2,2-difluoro-1-hydroxyethyl)-2-methyloxazol-5-yl)-2-(pyridin-2-ylmethyl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-7-(1-ethyl-1H-1,2,3-triazol-5-yl)-2-(pyridin-2-ylmethyl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-7-(1-methyl-1H-1,2,3-triazol-5-yl)-2-(pyridin-2-ylmethyl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(4-Amino-2-((2-fluorophenyl)(hydroxy)methyl)-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(2-fluorophenoxy)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(hydroxy(pyridin-2-yl)methyl)-5-(4-methyloxazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(2-(1-methyl-1H-pyrazol-4-yl)benzyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-5-(4-methyloxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-5-(4-ethyloxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-5-(3-methylpyridin-4-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(imidazo[1,2-a]pyridin-8-ylmethyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(pyrazolo[1,5-a]pyridin-7-ylmethyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(2-((2H-Indazol-2-yl)methyl)-8-amino-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(2-((1H-Indazol-1-yl)methyl)-8-amino-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-((2,5-difluorophenyl)(hydroxy)methyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-((2,3-difluorophenyl)(hydroxy)methyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-((2-fluorophenyl)(hydroxy)methyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-((2-chlorophenyl)(hydroxy)methyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(hydroxy(phenyl)methyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(phenylsulfonyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-(azetidine-1-carbonyl)-5-(4-methyloxazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-5-(6-hydroxypyridin-3-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(benzo[d]oxazol-4-ylmethyl)-5-(pyrimidin-4-yl)- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(2-fluoro-6-(1-methyl-1H-pyrazol-5-yl)benzyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

(R)-1-(2-((8-amino-6-(3-cyanophenyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorobenzyl)-3-methylpyrrolidine-3-carboxylic acid;

3-(8-amino-2-(2-fluoro-6-((6-methyl-5-oxo-2,6-diazaspiro[3.4]octan-2-yl)methyl)benzyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(2-fluoro-6-((6-oxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)methyl)benzyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

(S)-3-(8-amino-2-(2-fluoro-6-(((2-oxopyrrolidin-3-yl)amino)methyl)benzyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

2-((2-((8-amino-6-(3-cyanophenyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorobenzyl)amino)acetamide;

3-(8-amino-2-(2-fluoro-6-((3-oxopiperazin-1-yl)methyl)benzyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

(1S,3S)-3-((2-((8-amino-6-(3-cyanophenyl)-5-(pyrimidin-4-yl)- [1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorobenzyl)amino)cyclobutane-1-carboxylic acid

3-(8-amino-2-(2-fluoro-6-(((1-methyl-2-oxopyrrolidin-3-yl)amino)methyl)benzyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(2-fluoro-6-(((2-methyl-2H-1,2,3-triazol-4-yl)amino)methyl)benzyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

(S)-3-(8-amino-2-(2-(((2-oxopyrrolidin-3-yl)amino)methyl)benzyl)-5- (pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

(R)-1-(2-((8-amino-6-(3-cyanophenyl)-5-(4-methyloxazol-5-yl)- [1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorobenzyl)-3-methylpyrrolidine-3-carboxylic acid;

3-(8-amino-2-(amino(2,6-difluorophenyl)methyl)-5-(4-methyloxazol-5-yl)- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((2,6-difluorophenyl)(methylamino)methyl)-5-(4-methyloxazol-5 -yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((2,6-difluorophenyl)((2-hydroxyethyl)amino)methyl)-5-(4-methyloxazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(amino(2-fluorophenyl)methyl)-5-(4-methyloxazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(amino(2,6-difluorophenyl)methyl)-5-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((3-(oxazol-5-yl)pyridin-2-yl)methyl)-5-(pyrimidin-4-yl)- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(2-fluoro-6-(1-methyl-1H-pyrazol-4-yl)benzyl)- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

(S)-3-(8-amino-2-(2-fluoro-6-(((1-methyl-2-oxopyrrolidin-3-yl)amino)methyl)benzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-(2-fluoro-6-((6-methyl-5-oxo-2,6-diazaspiro[3.4]octan-2-yl)methyl)benzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-5-(4-methyloxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-5-(4-(2,2-difluoro-1-hydroxyethyl)-2-methyloxazol-5-yl)-2- (pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-5-(2-methyl-4-(2,2,2-trifluoro-1-hydroxyethyl)oxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile; 3-(8-amino-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-((1-((1-methyl-1H-imidazol-4-yl)sulfonyl)pyrrolidin-2-yl)methyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(2-(2-((1-acetylpiperidin-4-yl)methyl)-6-fluorobenzyl)-8-amino- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-5-(1-ethyl-1H-pyrazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-5-(2,6-dimethylpyridin- 4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(2-((1H-pyrrolo[3,2-b]pyridin-3-yl)methyl)-4-amino-7-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((2-(difluoromethoxy)-6-fluorophenyl)(hydroxy)methyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(2-fluoro-6-(1-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrazol- 4-yl)benzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-((2-((dimethylamino)methyl)-6-fluorophenyl)(hydroxy)methyl)- 5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-5-(3-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(5-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-8-amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-5-(oxazol-5-yl)- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(2-fluoro-6-(1-(pyridin-2-ylmethyl)-1H-pyrazol-4-yl)benzyl)- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-5-(3-methylpyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((2-fluoro-6-(pyrrolidin-1-ylmethyl)phenyl)(hydroxy)methyl)-5-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(2-fluoro-6-(1-(2-(methylsulfonyl)ethyl)-1H-pyrazol-4-yl)benzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-((2-fluoro-6-((6-oxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)methyl)phenyl)(hydroxy)methyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

2-(4-(2-((8-amino-6-(3-cyano-2-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorophenyl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide;

2-(4-(2-((8-amino-6-(3-cyano-2-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)-3-fluorophenyl)-1H-pyrazol-1-yl)acetamide;

3-(8-amino-2-(2-fluoro-6-(1-((trans)-3-(methylamino)cyclobutyl)-1H-pyrazol-4-yl)benzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-(2-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-6-fluorobenzyl)- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-(2-fluoro-6-(1-(2-(3-hydro\yazetidin-1-yl)-2-oxoethyl)-1H-pyrazol-4-yl)benzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-((3-methylpyridin-2-yl)methoxy)-5-(pyrimidin-4-yl)- [1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-2-((3-((1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl)amino)pyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-2-((3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)pyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-Amino-2-((3-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)-5- (pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

(S)-3-(8-Amino-2-(2-((3-hydroxypyrrolidin-1-yl)methyl)benzyl)-5- (pyrimidin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-Amino-5-(imidazo[1,2-a]pyridin-6-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-(azetidine-1-carbonyl)-5-(3-fluoropyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile;

3-(8-amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-5-(2,6-dimethylpyridin- 4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-2-fluorobenzonitrile;

3-(8-amino-5-(1-(methyl-d3)-6-oxo-1,6-dihydropyridazin-3-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile; and

3-(8-amino-2-((6-methoxypyridin-2-yl)methyl)-5-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile,

or a pharmaceutically acceptable salt thereof.

42. A pharmaceutical composition comprising a compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

43. A method of inhibiting an activity of an adenosine receptor, comprising contacting the receptor with a compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof.

44. A method of treating a disease or disorder in a patient, wherein the disease or disorder is associated with abnormal expression of A2A or A2B receptors, comprising administering to said patient a therapeutically effective amount of a compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof.

45. The method of claim 44, wherein the disease or disorder is cancer, an inflammatory disease, a cardiovascular disease, or a neurodegenerative disease.

46. The method of claim 45, wherein the cancer is bladder cancer, lung cancer, melanoma, breast cancer, cervical cancer, ovarian cancer, colorectal cancer, pancreatic cancer, esophageal cancer, prostate cancer, kidney cancer, skin cancer, thyroid cancer, liver cancer, uterine cancer, head and neck cancer, or renal cell carcinoma.

47. The method of claim 45, wherein the cancer is non-small cell lung cancer (NSCLC), metastatic castrate-resistant prostate carcinoma (mCRPC), or colorectal carcinoma (CRC).

48. The method of claim 45, wherein the inflammatory disease is pulmonary inflammation.

49. The method of claim 48, wherein the pulmonary inflammation is bleomycin-induced pulmonary fibrosis.

50. The method of claim 45, wherein the inflammatory disease is an adenosine receptor dependent allergic reaction or adenosine receptor immune reaction.

51. The method of claim 50, wherein the adenosine receptor dependent allergic reaction is A2B receptor dependent.

52. The method of claim 45, wherein the inflammatory disease is a respiratory disorder, sepsis, reperfusion injury, or thrombosis.

53. The method of claim 45, wherein the cardiovascular disease is coronary artery disease, cerebrovascular disease, peripheral artery disease, aortic atherosclerosis, or aneurysm.

54. The method of claim 53, wherein the coronary artery disease is myocardial infarction, angina pectoris, or heart failure.

55. The method of claim 53, wherein the cerebrovascular disease is stroke or transient ischemic attack.

56. The method of claim 45, wherein the neurodegenerative disease is Parkinson’s disease.

57. The method of claim 44, wherein the disease or disorder is diabetes or insulin resistance.

58. A method of treating or preventing atherosclerotic plaque formation in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof.