Imidazopyrimidines and triazolopyrimidines as a2a / a2b inhibitors

Abstract

This application relates to compounds of Formula (I): or pharmaceutically acceptable salts or stereoisomers thereof, which modulate the activity of adenosine receptors, such as subtypes A2A and A2B receptors, and are useful in the treatment of diseases related to the activity of adenosine receptors including, for example, cancer, inflammatory diseases, cardiovascular diseases, and neurodegenerative diseases.

1 . (canceled) 
     
     
         2 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof; wherein:
 X is N; 
 R 1  is selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, and C 1-6  haloalkyl; 
 R 2  is selected from C 1-6  alkyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , and NR c2 R d2 , wherein the C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 independently selected R C  substituents; and 
 wherein the C 1-6  alkyl of R 2  is substituted with 1, 2, 3, 4, or 5 independently selected R C  substituents; 
 Cy 1  is 3-cyanophenyl; 
 Cy 2  is C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R F  substituents; 
 each R a2 , R c2 , and R d2  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R a2 , R c2 , and R d2  are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R G  substituents; 
 or any R c2  and R d2  attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R G  substituents; 
 each R b2  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R b2  are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R G  substituents; 
 each R C , R F , and R G  is independently selected from D, halo, oxo, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-54  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, CN, NO 2 , OR a4 , SR a4 , NHOR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)NR c4 (R a4 ), C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 NR c4 R d4 , NR c4 C(O)R b4 , NR e4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , C(═NR e4 )R b4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )R b4 , NR c4 S(O)R b4 , NR c4 S(O)NR c4 R d4 , NR c4 S(O) 2 R b4 , NR c4 S(O)(═NR e4 )R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , S(O) 2 NR c4 R d4 , OS(O)(═NR e4 )R b4 , OS(O) 2 R b4 , SF 5 , P(O)R f4 R g4 , OP( )(OR h4 )(OR i4 ), P(O)(R h4 )(OR i4 ), and BR j4 R k4 , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R C , R F , and R G  are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H  substituents; 
 each R a4 , R c4  and R d4  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R a4 , R c4 , and R d4  are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H  substituents; 
 or, any R c4  and R d4  attached to the same N atom, together with the N atom to which they are attached, optionally form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R H  substituents; 
 each R b4  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R b4  are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H  substituents; 
 each R e4  is independently selected from H, OH, CN, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R f4  and R g4  is independently selected from H, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R h4  and R i4  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R j4  and R k4  is independently selected from OH, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
 or, any R j4  and R k4  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 C 1-6  alkyl and C 1-6  haloalkyl; 
 each R H  is independently selected from D, halo, oxo, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, CN, NO 2 , OR a5 , SR a5 , NHOR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)NR c5 (OR a5 ), C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , C(═NR e5 )R b5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )R b5 , NR c5 S(O)R b5 , NR c5 S(O)NR c5 R d5 , NR c5 S(O) 2 R b5 , NR c5 S(O)(═NR e5 )R b5 , NR c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , S(O) 2 NR c5 R d5 , OS(O)(═NR e5 )R b5 , OS(O) 2 R b5 , SF 5 , P(O)R f5 R g5 , OP(O)(OR h5 )(OR i5 ), P(O)(OR h5 )(OR i5 ), and BR j5 R k5 , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R H  are each optionally substituted with 1, 2, 3, or 4 independently selected R I  substituents; 
 each R a5 , R c5 , and R d5  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R a5 , R c5 , and R d5  are each optionally substituted with 1, 2, 3, or 4 independently selected R I  substituents; 
 or any R c5  and R d5  attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R I  substituents; 
 each R b5  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R b5  are each optionally substituted with 1, 2, 3, or 4 independently selected R I  substituents; 
 each R e5  is independently selected from H, OH, CN, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R f5  and R g5  is independently selected from H, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R h5  and R i5  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R j5  and R k5  is independently selected from OH, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
 or, any R j5  and R k5  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 C 1-6  alkyl and C 1-6  haloalkyl; 
 each R I  is independently selected from D, halo, oxo, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, CN, NO 2 , OR a6 , SR a6 , NHOR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)NR c6 (OR a6 ), C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , C(═NR e6 )R b6 , C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )R b6 , NR c6 S(O)R b6 , NR c6 S(O)NR c6 R d6 , NR c6 S(O) 2 R b6 , NR c6 S(O)(═NR e6 )R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , S(O) 2 NR c6 R d6 , OS(O)(═NR e6 )R b6 , OS(O) 2 R b6 , SF 5 , P(O)R f6 R g6 , OP(O)(OR h6 )(OR i6 ), P(O)(OR h6 )(OR i6 ), and BR j6 R k6 , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R I  are each optionally substituted with 1, 2, 3, or 4 independently selected R J  substituents; 
 each R a6 , R c6 , and R d6  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R a6 , R c6 , and R d6  are each optionally substituted with 1, 2, 3, or 4 independently selected R J  substituents; 
 or any R c6  and R d6  attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R J  substituents; 
 each R b6  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R b6  are each optionally substituted with 1, 2, 3, or 4 independently selected R J  substituents; 
 each R e6  is independently selected from H, OH, CN, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R f6  and R g6  is independently selected from H, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R h6  and R i6  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R j6  and R k6  is independently selected from OH, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
 or, any R j6  and R k6  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 C 1-6  alkyl and C 1-6  haloalkyl; 
 each R J  is independently selected from D, halo, oxo, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, CN, NO 2 , OR a7 , SR a7 , NHOR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)NR c7 (OR a7 ), C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 C(O)NR c7 R d7 , C(═NR e7 )R b7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )R b7 , NR c7 S(O)R b7 , NR c7 S(O)NR c7 R d7 , NR c7 S(O) 2 R b7 , NR c7 S(O)(═NR e7 )R b7 , NR c7 S(O) 2 NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , S(O) 2 NR c7 R d7 , OS(O)(═NR e7 )R b7 , OS(O) 2 R b7 , SF 5 , P(O)R f7 R g7 , OP(O)(OR h7 )(OR i7 ), P(O)(OR h7 )(OR i7 ), and BR j7 R k7 , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R J  are each optionally substituted with 1, 2, 3, or 4 independently selected R K  substituents; 
 each R a7 , R c7 , and R d7  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R a7 , R c7 , and R d7  are each optionally substituted with 1, 2, 3, or 4 independently selected R K  substituents; 
 or any R c7  and R d7  attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R K  substituents; 
 each R b7  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R b7  are each optionally substituted with 1, 2, 3, or 4 independently selected R K  substituents; 
 each R e7  is independently selected from H, OH, CN, C 1-6  alkyl, C 2-6  alkenyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl; 
 each R f7  and R g7  is independently selected from H, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R h7  and R i7  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; 
 each R j7  and R k7  is independently selected from OH, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
 or, any R j7  and R k7  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 C 1-6  alkyl and C 1-6  haloalkyl; 
 each R K  is independently selected from H, D, OH, halo, oxo, CN, C(O)OH, NH 2 , NO 2 , SF 5 , C 1-6  alkyl, C 1-6  alkoxy, C 1-6  haloalkoxy, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-; and 
 wherein any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen. 
 
     
     
         3 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein:
 each R J  is independently selected from D, halo, oxo, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, CN, NO 2 , OR a7 , SR a7 , NHOR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)NR c7 (OR a7 ), C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 C(O)NR c7 R d7 , C(═NR e7 )R b7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )R b7 , NR c7 S(O)R b7 , NR c7 S(O)NR c7 R d7 , NR c7 S(O) 2 R b7 , NR c7 S(O)(═NR e7 )R b7 , NR c7 S(O) 2 NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , S(O) 2 NR c7 R d7 , OS(O)(═NR e7 )R b7 , OS(O) 2 R b7 , SF 5 , P(O)R f7 R g7 , OP(O)(OR h7 )(OR i7 ), P(O)(OR h7 )(OR i7 ), and BR j7 R k7 ;   each R a7 , R c7 , and R d7  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-;   or any R c7  and R d7  attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14-membered heterocycloalkyl group; and   each R b7  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-.   
     
     
         4 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein:
 each R I  is independently selected from D, halo, oxo, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, CN, NO 2 , OR a6 , SR a6 , NHOR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)NR c6 (OR a6 ), C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , C(═NR e6 )R b6 , C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )R b6 , NR c6 S(O)R b6 , NR c6 S(O)NR c6 R d6 , NR c6 S(O) 2 R b6 , NR c6 S(O)(═NR e6 )R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , S(O) 2 NR c6 R d6 , OS(O)(═NR e6 )R b6 , OS(O) 2 R b6 , SF 5 , P(O)R f6 R g6 , OP(O)(OR h6 )(OR i6 ), P(O)(OR h6 )(OR i6 ), and BR j6 R k6 ;   each R a6 , R c6 , and R d6  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-;   or any R c6  and R d6  attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14-membered heterocycloalkyl group; and   each R b6  is independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl-.   
     
     
         5 - 13 . (canceled) 
     
     
         14 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein Cy 2  is C 6-14  aryl, wherein the C 6-14  aryl is optionally substituted with 1, 2, 3, or 4 independently selected R F  substituents. 
     
     
         15 . (canceled) 
     
     
         16 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein Cy 2  is 5-14 membered heteroaryl, wherein the 5-14 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 independently selected R F  substituents. 
     
     
         17 . The compound  claim 2 , or a pharmaceutically acceptable salt thereof, wherein Cy 2  is 4-14 membered heterocycloalkyl, wherein the 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R F  substituents. 
     
     
         18 . (canceled) 
     
     
         19 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein Cy 2  is selected from pyridinyl, tetrahydropyridinyl, piperidinyl, pyridine-N-oxide, oxo-dihydropyridinyl, phenyl, pyrazolo[1,5-a]pyridin-3-yl, pyrazolo[1,5-b]pyridazinyl, pyrazolyl, pyrimidinyl, quinolinyl, oxazolyl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-yl, and triazolyl each of which is optionally substituted with 1, 2, or 3 substituents selected from C 1-3  alkyl, C 1-3  alkyl-OH, halo, CN, C 1-3  alkoxy, and C(O)NH 2 . 
     
     
         20 . (canceled) 
     
     
         21 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted Cy 2  is selected from 2,6-dimethylpyridin-4-yl, pyridin-4-yl, 2-methylpyridin-4-yl, 1-carbamoyl-1,2,3,6-tetrahydropyridin-4-yl, 1-carbamoylpiperidin-4-yl, 2-methoxypyridin-4-yl, 2-methoxy-6-methylpyridin-4-yl, 2,6-dimethylpyridin-4-yl-1-oxide, 1-ethyl-6-oxo-1,6-dihydropyridin-3-yl, 3-methylpyridin-4-yl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 3-methoxypyridin-4-yl, 3-cyanopyridin-4-yl, 4-carbamoylphenyl, pyrazolo[1,5-a]pyridin-3-yl, pyrazolo[1,5-b]pyridazin-3-yl, 5-methyl-1H-pyrazol-4-yl, 1-ethyl-1H-pyrazol-5-yl, 1-isopropyl-1H-pyrazol-5-yl, 1-propyl-1H-pyrazol-5-yl, pyrimidin-4-yl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-yl, quinolin-5-yl, 5-fluoropyrimidin-4-yl, oxazol-5-yl, 4-methyloxazol-5-yl, 4-ethyloxazol-5-yl, 4-(hydroxymethyl)-2-methyloxazol-5-yl, 4-(methoxymethyl)-2-methyloxazol-5-yl, 4-(hydroxymethyl)-2-methyloxazol-5-yl, 1-ethyl-1H-1,2,3-triazol-5-yl, and cyclopropyl. 
     
     
         22 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from H and C 1-6  alkyl. 
     
     
         23 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1  is H or C 1-3  alkyl. 
     
     
         24 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1  is H or ethyl. 
     
     
         25 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1  is H. 
     
     
         26 - 31 . (canceled) 
     
     
         32 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted R 2  is selected from pyridinylmethyl, hydroxy(phenyl)methyl, hydroxyethylamino(phenyl)ethyl, cyclohexylmethyl, fluorobenzyl, hydroxy(fluorophenyl)methyl, (methylpyridinyl)methyl, (fluoropyridinyl)methyl, (trifluoromethylpyridinyl)methyl, ((hydroxymethyl)pyridinyl)methyl, (methoxypyridinyl)methyl, (methylpyrazolyl)benzyl, (methylpyrazolyl)methyl, benzoisoxazolylmethyl, (methylindazolyl)methyl, (hydroxyazetidinyl)methyl, benzoyl, phenylcyclopropyl, (cyano(phenyl)methyl)amino, tetrahydrofuranyl, phenyl(pyridinyloxy)methyl, fluoro ((fluorohydroxypyrrolidinyl)methyl)benzyl, ((carboxypiperidinyl)methyl)fluorobenzyl, fluoro((N-methylmethylsulfonamido)methyl)benzyl, ((dioxoimidazolidinyl)methyl)fluorobenzyl, (difluorophenyl)(hydroxy)methyl, (pyridinyl-1H-tetrazolyl)methyl, (pyrazolyl-1H-tetrazolyl)methyl, (thiazolyl-1H-tetrazolyl)methyl, (methyltrifluoromethylpyrazolyl)methyl, ((1,1-dioxidoisothiazolidinyl)methyl)fluorobenzyl, ((methyl-2,5-dioxoimidazolidinyl)methyl)benzyl, and (cyanophenoxy)methyl. 
     
     
         33 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted R 2  is selected from pyridin-2-ylmethyl, hydroxy(phenyl)methyl, (2-hydroxyethylamino)(phenyl)methyl, cyclohexylmethyl, 2-fluorobenzyl, (2-fluorophenyl)(hydroxy)methyl, (6-methylpyridin-2-yl)methyl, (3-fluoropyridin-2-yl)methyl, (3-methoxypyridin-2-yl)methyl, 2-(1-methyl-1H-pyrazol-4-yl)benzyl, benzo[d]isoxazol-3-ylmethyl, (1-methyl-1H-indazol-3-yl)methyl, (3-hydroxyazetidin-1-yl)methyl, benzoyl, 1-phenylcyclopropyl, (cyano(phenyl)methyl)amino, tetrahydrofuran-3-yl, phenyl(pyridin-2-yloxy)methyl, 2-fluoro-6-(((3R,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl)methyl)benzyl, 2-((4-carboxypiperidin-1-yl)methyl)-6-fluorobenzyl, 2-fluoro-6-((N-methylmethylsulfonamido)methyl)benzyl, 2-((2,5-dioxoimidazolidin-1-yl)methyl)-6-fluorobenzyl, (2,6-difluorophenyl)(hydroxy)methyl, (5-(pyridin-2-yl)-1H-tetrazol-1-yl)methyl, (5-(1H-pyrazol-1-yl)-1H-tetrazol-1-yl)methyl, (5-(thiazol-4-yl)-1H-tetrazol-1-yl)methyl, (5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl, (3-methylpyridin-2-yl)methyl, 2-((1,1-dioxidoisothiazolidin-2-yl)methyl)-6-fluorobenzyl, 2-fluoro-6-((3-methyl-2,5-dioxoimidazolidin-1-yl)methyl)benzyl, (6-(trifluoromethyl)pyridin-2-yl)methyl, (3-(hydroxymethyl)pyridin-2-yl)methyl, (1-methyl-1H-pyrazol-3-yl)methyl, and (2-cyanophenoxy)methyl, and ((3-methylpyridin-2-yl)methyl)amino. 
     
     
         34 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein each R C  is independently selected from halo, C 1-6  alkyl, C 6-14  aryl, 5-14 membered heteroaryl, (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, OR a4 , C(O)OR a4 , and NR c4 R d4 , wherein the C 1-6  alkyl, 5-14 membered heteroaryl, and (4-14 membered heterocycloalkyl)-C 1-6  alkyl- are optionally substituted with 1, 2, or 3 independently selected R H  substituents. 
     
     
         35 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein each R H  is independently selected from halo, oxo, C 1-6  alkyl, C 1-6  haloalkyl, OR a5 , C(O)OR a5 , and NR c5 S(O) 2 R b5 . 
     
     
         36 - 40 . (canceled) 
     
     
         41 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof;
 wherein:   R 1  is selected from H and C 1-6  alkyl;   R 2  is selected from C 6-14  aryl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, (4-14 membered heterocycloalkyl)-C 1-6  alkyl-, NR c2 R d2 , C(O)R b2 , C(O)NR c2 R d2 , and C(O)OR a2 , wherein the C 6-14  aryl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-14  aryl-C 1-6  alkyl-, (5-14 membered heteroaryl)-C 1-6  alkyl-, (4-14 membered heterocycloalkyl)-C 1-6  alkyl- of R 2  are each optionally substituted with 1, 2, 3, or 4 independently selected R C  substituents;   Cy 2  is C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl or 4-14 membered heterocycloalkyl, wherein the C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl and 4-14 membered heterocycloalkyl of Cy 2  are each optionally substituted with 1, 2, 3, or 4 independently selected R F  substituents;   each R a2 , R c2 , and R d2  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 6-14  aryl-C 1-6  alkyl-, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl of R a2 , R c2 , and R d2  are each optionally substituted with 1, 2, 3, or 4 independently selected R G  substituents;   each R b2  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R G  substituents;   each R C , R F , and R G  is independently selected from D, halo, oxo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CN, NO 2 , OR a4 , SR a4 , NHOR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , C(═NR e4 )R b4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , and NR c4 S(O) 2 NR c4 R d4 , wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl of R C , R F , and R G  are each optionally substituted with 1, 2, 3, or 4 independently selected R H  substituents;   each a R a4 , R c4 , and R d4  is independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl of R a4 , R c4 , and R d4  are each optionally substituted with 1, 2, 3, or 4 independently selected R H  substituents;   each R b4  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R H  substituents;   each R H  is independently selected from D, halo, oxo, C 1-6  alkyl, CN, NO 2 , OR a5 , SR a5 , NHOR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , C(═NR e5 )R b5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , NR c5 S(O)R b5 , NR c5 S(O) 2 R b5 , and NR c5 S(O) 2 NR c5 R d5 ; and   each R a5 , R c5 , and R d5  is independently selected from H, and C 1-6  alkyl;   each R b5  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-14  aryl, C 3-14  cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl; and   each R e5  is independently selected from H and C 1-6  alkyl.   
     
     
         42 . (canceled) 
     
     
         43 . The compound of  claim 2 , selected from:
 3-(5-Amino-2-(pyridin-2-ylmethyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(1-ethyl-1H-pyrazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(1-propyl-1H-pyrazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-(pyridin-2-ylmethyl)-8-(quinolin-5-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(5-fluoropyrimidin-4-yl)-2-(hydroxy(phenyl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(5-fluoropyrimidin-4-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((2-hydroxyethylamino)(phenyl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-(cyclohexylmethyl)-8-(1-ethyl-1H-pyrazol-5-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-(2-fluorobenzyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((2-fluorophenyl)(hydroxy)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((6-methylpyridin-2-yl)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(1-ethyl-1H-pyrazol-5-yl)-2-((3-fluoropyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(1-ethyl-1H-pyrazol-5-yl)-2-((3-methoxypyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-(2-(1-methyl-1H-pyrazol-4-yl)benzyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-(benzo[d]isoxazol-3-ylmethyl)-8-(1-ethyl-1H-pyrazol-5-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(1-ethyl-1H-pyrazol-5-yl)-2-((1-methyl-1H-indazol-3-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((3-hydroxyazetidin-1-yl)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(3-methylpyridin-4-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(2-methoxy-6-methylpyridin-4-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(pyrazolo[1,5-b]pyridazin-3-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(4-methyloxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(4-(hydroxymethyl)-2-methyloxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(4-(methoxymethyl)-2-methyloxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   (S)-3-(5-amino-2-(hydroxy(phenyl)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   (R)-3-(5-amino-2-(hydroxy(phenyl)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-benzoyl-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(1-ethyl-1H-pyrazol-5-yl)-2-(1-phenylcyclopropyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((cyano(phenyl)methyl)amino)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(pyridin-4-yl)-2-(tetrahydrofuran-3-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile; and   3-(5-Amino-2-(phenyl(pyridin-2-yloxy)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   or a pharmaceutically acceptable salt thereof.   
     
     
         44 . The compound of  claim 2 , selected from:
 3-(5-Amino-2-(2-fluoro-6-(((3R,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl)methyl)benzyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   1-(2-((5-Amino-7-(3-cyanophenyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)methyl)-3-fluorobenzyl)piperidine-4-carboxylic acid;   N-(2-((5-Amino-7-(3-cyanophenyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)methyl)-3-fluorobenzyl)-N-methylmethanesulfonamide;   3-(5-Amino-2-(2-((2,5-dioxoimidazolidin-1-yl)methyl)-6-fluorobenzyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile; and   3-(5-Amino-2-((2,6-difluorophenyl)(hydroxy)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   or a pharmaceutically acceptable salt thereof.   
     
     
         45 . The compound of  claim 2 , selected from:
 3-(5-Amino-2-((5-(pyridin-2-yl)-1H-tetrazol-1-yl)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(2-((5-(1H-Pyrazol-1-yl)-1H-tetrazol-1-yl)methyl)-5-amino-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(pyrimidin-4-yl)-2-((5-(thiazol-4-yl)-1H-tetrazol-1-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(4-ethyloxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(1-ethyl-1H-1,2,3-triazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(4-methyloxazol-5-yl)-2-((3-methylpyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((3-fluoropyridin-2-yl)methyl)-8-(4-(hydroxymethyl)-2-methyloxazol-5-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-(2-((1,1-dioxidoisothiazolidin-2-yl)methyl)-6-fluorobenzyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-(2-fluoro-6-((3-methyl-2,5-dioxoimidazolidin-1-yl)methyl)benzyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((3-fluoropyridin-2-yl)methyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(4-methyloxazol-5-yl)-2-((6-(trifluoromethyl)pyridin-2-yl)methyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-8-(4-methyloxazol-5-yl)-2-(pyridin-2-ylmethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)-2-fluorobenzonitrile;   3-(5-Amino-2-((3-(hydroxymethyl)pyridin-2-yl)methyl)-8-(4-methyloxazol-5-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((1-methyl-1H-pyrazol-3-yl)methyl)-8-(4-methyloxazol-5-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   3-(5-Amino-2-((1-methyl-1H-pyrazol-3-yl)methyl)-8-(oxazol-5-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   2-((5-Amino-7-(3-cyanophenyl)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)methoxy)benzonitrile; and   3-(5-Amino-2-(((3-methylpyridin-2-yl)methyl)amino)-8-(pyrimidin-4-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl)benzonitrile;   or a pharmaceutically acceptable salt thereof.   
     
     
         46 . A pharmaceutical composition comprising a compound of  claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier. 
     
     
         47 . A method of inhibiting an activity of an adenosine receptor, comprising contacting the receptor with a compound of  claim 2 , or a pharmaceutically acceptable salt thereof. 
     
     
         48 . 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  claim 2 , or a pharmaceutically acceptable salt thereof. 
     
     
         49 . The method of  claim 48 , wherein the disease or disorder is cancer, an inflammatory disease, a cardiovascular disease, or a neurodegenerative disease. 
     
     
         50 . The method of  claim 49 , 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, or renal cell carcinoma. 
     
     
         51 . The method of  claim 49 , wherein the inflammatory disease is pulmonary inflammation. 
     
     
         52 . The method of  claim 51 , wherein the pulmonary inflammation is bleomycin-induced pulmonary fibrosis. 
     
     
         53 . The method of  claim 49 , wherein the inflammatory disease is an adenosine receptor dependent allergic reaction or adenosine receptor immune reaction. 
     
     
         54 . The method of  claim 53 , wherein the adenosine receptor dependent allergic reaction is A2B receptor dependent. 
     
     
         55 . The method of  claim 49 , wherein the inflammatory disease is a respiratory disorder, sepsis, reperfusion injury, or thrombosis. 
     
     
         56 . The method of  claim 49 , wherein the cardiovascular disease is coronary artery disease, cerebrovascular disease, peripheral artery disease, aortic atherosclerosis, or aneurysm. 
     
     
         57 . The method of  claim 56 , wherein the coronary artery disease is myocardial infarction, angina pectoris, or heart failure. 
     
     
         58 . The method of  claim 56 , wherein the cerebrovascular disease is stroke or transient ischemic attack. 
     
     
         59 . The method of  claim 49 , wherein the neurodegenerative disease is Parkinson's disease. 
     
     
         60 . The method of  claim 48 , wherein the disease or disorder is diabetes or insulin resistance. 
     
     
         61 . 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  claim 2 , or a pharmaceutically acceptable salt thereof.