Purinone derivatives as hm74a agonists

Abstract

The present invention relates to purinone derivatives which are agonists of the HM74a receptor. Further provided are compositions and methods of using the compounds herein, and their pharmaceutically acceptable salts for the treatment of disease.

What is claimed is: 
     
         1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt or prodrug thereof, wherein:
 a dashed line indicates an optional bond; 
 X is N, CR 3a , CR 4a R 5a , or NR 6a ; 
 Y is N, CR 3b , CR 4b R 5b , or NR 6b ; 
 L is —(C 1-6  alkylene)-(Q 1 ) m -(C 1-6  alkylene) p -(Q 2 ) q -(C 1-6  alkylene) r -, optionally substituted with 1, 2, 3, 4, or 5 R L1 , wherein if m and q are both 1, then p is 1; 
 R 1  is H, C 1-10  alkyl, C 2-10  alkenyl, C 2-10  alkynyl, or Cy, wherein said C 1-10  alkyl, C 2-10  alkenyl, or C 2-10  alkynyl is optionally substituted with 1, 2, 3, 4, or 5 R L2 ; 
 R 2  is halo, cyano, C 1-3  haloalkyl, Z, SR A , or a moiety having the formula: 
 
       
       
         
           
           
               
               
           
         
         
           R 3a  and R 3b  are independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 1 , CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , NR c S(O) 2 R b , and S(O) 2 NR c R d , wherein said C 1-6  alkyl, C 2-6  alkenyl, or C 2-6  alkynyl is optionally substituted with 1, 2, or 3 substitutents independently selected from Cy 1 , CN, NO 2 , halo, OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , NR c S(O) 2 R b , and S(O) 2 NR c R d ; 
           R 4a , R 4b , R 5a , and R 5b  are independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 2 , CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR c1 S(O) 2 R b1 , and S(O) 2 NR c1 R d1 , wherein said C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl are optionally substituted with 1, 2, or 3 substitutents independently selected from Cy 2 , CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR c1 S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; 
           R 6a  and R 6b  are independently selected from H, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, Cy 2 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR c1 S(O) 2 R b1 , and S(O) 2 NR c1 R d1 , wherein said C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl are optionally substituted with 1, 2, or 3 substitutents independently selected from Cy 2 , CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR a S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; 
           R L1  and R L2  are independently selected from halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)NR c2 R d2 , NR c2 C(O)OR a2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ; 
           R 2a  is H, C 1-6  alkyl, C 2-6  alkenyl, C 2-10  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 4 , CN, NO 2 , C(O)R b6 , C(O)NR c6 R d6 , or C(O)OR a6 ; 
           Cy is aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; 
           Cy 1  and Cy 2  are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, CN, NO 2 , OR a4 , SR 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 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , S(O) 2 NR c4 R d4 , and Cy 3 , wherein said C 1-4  alkyl, C 2-4  alkenyl, or C 2-4  alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from CN, NO 2 , halo, OR a4 , SR 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 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , S(O) 2 NR c4 R d4 , and Cy 3 ; 
           Cy 3  and Cy 4  are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, CN, NO 2 , OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 ; 
           Z is aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, CN, NO 2 , OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 ; 
           R A  is H or C 1-4  alkyl; 
           Q 1  and Q 2  are independently selected from O, S, NH, CH 2 , CO, CS, SO, SO 2 , OCH 2 , SCH 2 , NHCH 2 , CH 2 CH 2 , COCH 2 , CONH, COO, SOCH 2 , SONH, SO 2 CH 2 , and SO 2 NH; 
           R a  and R a1  are independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, and Cy 2 , wherein said C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, or C 2-6  alkynyl, is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 2 , CN, NO 2 , OR a5 , SR 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)NR c5 R d5 , NR c5 C(O)OR a5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; 
           R a2 , R a3 , R a4 , R a5 , and R a6  are independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, cyano, amino, halo, C 1-6  alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; 
         
         R b  and R b1  are independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, and Cy 2 , wherein said C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, or C 2-6  alkynyl, is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 2 , CN, NO 2 , OR a5 , SR 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)NR c5 R d5 , NR c5 C(O)OR a5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ;
 R b2 , R b3 , R b4 , R b5 , and R b6  are independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, cyano, amino, halo, C 1-6  alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; 
 R c  and R d  are independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, and Cy 2 , wherein said C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, or C 2-6  alkynyl, is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 2 , CN, NO 2 , OR a5 , SR 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)NR c5 R d5 , NR c5 C(O)OR a5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; 
 or R c  and R d  together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 2 , CN, NO 2 , OR a5 , SR 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)NR c5 R d5 , NR c5 C(O)OR a5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; 
 R c1  and R d1  are independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, and Cy 2 , wherein said C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, or C 2-6  alkynyl, is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 2 , CN, NO 2 , OR a5 , SR 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)NR c5 R d5 , NR c5 C(O)OR a5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; 
 or R c1  and R d1  together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  cyanoalkyl, Cy 2 , CN, NO 2 , OR a5 , SR 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)NR c5 R d5 , NR c5 C(O)OR a5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; 
 R c2  and R d2  are independently selected from H, C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6  alkyl, C 1-6  haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; 
 or R c2  and R d2  together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; 
 R c3  and R d3  are independently selected from H, C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6  alkyl, C 1-6  haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; 
 or R c3  and R d3  together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; 
 R c4  and R d4  are independently selected from H, C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6  alkyl, C 1-6  haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; 
 or R c4  and R d4  together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; 
 R c5  and R d5  are independently selected from H, C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6  alkyl, C 1-6  haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; 
 or R c5  and R d5  together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; and 
 
         R c6  and R d6  are independently selected from H, C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6  alkyl, C 1-6  haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl;
 or R c6  and R d6  together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; and 
 m, p, q, and r are independently selected from 0 and 1, 
 
         with the provisos:
 (a) when X Y is CR 4a R 5a —CR 4b R 5b , then R 2  is other than halo, C 1-3  haloalkyl, Z or SR A ; 
 (b) when X Y is CR 3a ═N, then R 2  is other than Z; 
 (c) when X Y is N═CR 3b  and R 3b  is H or unsubstituted aryl, then R 2  is other than unsubstituted aryl; 
 (d) when X Y is N═N, then R 2  is other than aryl; and 
 (e) when X Y is CR 3a ═CR 3b , then -L-R1 is other than methyl. 
 
       
     
     
         2 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein X is N. 
     
     
         3 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein X is CH. 
     
     
         4 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein Y is CR 3b . 
     
     
         5 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein Y is CH. 
     
     
         6 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein Y is C-Me. 
     
     
         7 . (canceled) 
     
     
         8 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3a  and R 3b  are independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, Cy 1 , OR a , SR a , S(O)R b , S(O) 2 R b , and NR c R d , wherein said C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl are optionally substituted with 1, 2, or 3 substitutents independently selected from Cy 1 , CN, NO 2 , halo, OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , NR c S(O) 2 R b , and S(O) 2 NR c R d . 
     
     
         9 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3a  and R 3b  are independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, Cy 1 , OR a , SR a , and NR c R d , wherein said C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl are optionally substituted with 1, 2, or 3 substitutents independently selected from Cy 1 , CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , NR c S(O) 2 R b , and S(O) 2 NR c R d . 
     
     
         10 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3a  and R 3b  are independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, Cy 1 , OR a , SR a , and NR c R d , wherein said C 1-6  alkyl, C 2-6  alkenyl, and C 2-6  alkynyl are optionally substituted with 1, 2, or 3 substitutents independently selected from Cy 1 , C(O)NR c R d , C(O)OR a , and NR c C(O)R b . 
     
     
         11 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3a  and R 3b  are independently selected from H, C 1-6  alkyl, C 1-6  haloalkyl, Cy 1 , halo, OR a , SR a , S(O)R b , S(O) 2 R b , and NR c R d , wherein said C 1-6  alkyl is optionally substituted with 1, 2, or 3 substitutents independently selected from Cy 1 , C(O)NR c R d , C(O)OR a , halo, OR a , NR c R d , NR c C(O)NR c R d , and NR c C(O)R b . 
     
     
         12 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein:
 at least one of R 3a  and R 3b  is selected from Cy 1 ;   Cy 1  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , and Cy 3 , wherein said C 1-4  alkyl, C 2-4  alkenyl, and C 2-4  alkynyl are optionally substituted with 1, 2, or 3 substituents independently selected from halo, OR a4  and Cy 3 ; and   Cy 3  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, aryl, heteroaryl, CN, NO 2 , NR c6 R d6 , OR a6 , and SR a6 .   
     
     
         13 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein at least one of R 3a  and R 3b  is selected from C 1-6  alkyl and C 1-6  haloalkyl, wherein said C 1-6  alkyl is optionally substituted with 1, 2, or 3 substitutents independently selected from C(O)NR c R d , C(O)OR a , NR c R d , NR c C(O)NR c R d , and NR c C(O)R b . 
     
     
         14 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein:
 at least one of R 3a  and R 3b  is selected from C 1-3  alkyl, wherein said C 1-3  alkyl is substituted with Cy 1  and optionally substituted with 1 or 2 substitutents independently selected from halo, OR a , and SR a ;   Cy 1  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, CN, NO 2 , OR a4 , SR 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 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , S(O) 2 NR c4 R d4 , and Cy 3 , wherein said C 1-4  alkyl, C 2-4  alkenyl, and C 2-4  alkynyl are optionally substituted with 1, 2, or 3 substituents independently selected from OR a4  and Cy 3 ; and   Cy 3  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, CN, NO 2 , OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 .   
     
     
         15 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein:
 at least one of R 3a  and R 3b  is selected from C 1-3  alkyl, wherein said C 1-3  alkyl is substituted with Cy 1  and optionally substituted with 1 or 2 substitutents independently selected from halo, OR a , and SR a ;   Cy 1  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , and Cy 3 , wherein said C 1-4  alkyl, C 2-4  alkenyl, and C 2-4  alkynyl are optionally substituted with 1, 2, or 3 substituents independently selected from OR a4  and Cy 3 ; and   Cy 3  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, aryl, heteroaryl, CN, NO 2 , NR c6 R d6 , OR a6 , and SR a6 .   
     
     
         16 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein:
 at least one of R 3a  and R 3b  is independently selected from C 1-3  alkyl, wherein said C 1-3  alkyl is substituted with Cy 1  and optionally substituted with 1 or 2 substitutents independently selected from halo, OR a , and SR a ;   Cy 1  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each substituted with 1 or 2 R 7  and optionally substituted by 1, 2, or 3 R 8 ;   R 7  is, at each occurrence, independently selected from Cy 3  and C 1-4  alkyl, wherein said C 1-4  alkyl is substituted with 1 or 2 Cy 3  and optionally substituted with 1 or 2 substituents independently selected from halo and OR a4 ;   R 8  is, at each occurrence, independently selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , and C(O)OR a4 ; and   Cy 3  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, aryl, heteroaryl, CN, NO 2 , NR c6 R d6 , OR a6 , and SR a6 .   
     
     
         17 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3a  and R 3b  are independently selected from H, halo, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, and C 1-6  haloalkyl. 
     
     
         18 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3a  and R 3b  are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl. 
     
     
         19 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3b  is heteroaryl optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from aryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, CN, NO 2 , OR a6 , and SR a6 . 
     
     
         20 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 3b  is thiazolyl that is optionally substituted with phenyl, wherein said phenyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH and halo. 
     
     
         21 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein Cy 1  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, CN, NO 2 , OR a4 , SR 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 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , S(O) 2 NR c4 R d4 , and Cy 3 , wherein said C 1-4  alkyl, C 2-4  alkenyl, and C 2-4  alkynyl are optionally substituted with 1, 2, or 3 substituents independently selected from OR a4  and Cy 3 . 
     
     
         22 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein m and q are 0. 
     
     
         23 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 1  is H or C 1-10  alkyl. 
     
     
         24 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein -L-R 1  is C 1-10  alkyl. 
     
     
         25 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein -L-R 1  is C 4-7  alkyl optionally substituted with 1, 2, 3, 4 or 5 substitutents each independent selected from halo, OH, and CN. 
     
     
         26 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein -L-R 1  is butyl or pentyl. 
     
     
         27 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is halo, cyano, C 1  haloalkyl, Z, SR A , or a moiety having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         28 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is halo, cyano, C 1  haloalkyl, Z, or, SR A . 
     
     
         29 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is halo, cyano, or C 1  haloalkyl. 
     
     
         30 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is halo or C 1  haloalkyl. 
     
     
         31 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is Cl, Br, or CF 3 . 
     
     
         32 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is Cl or Br. 
     
     
         33 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is Br. 
     
     
         34 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  a moiety having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         35 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is S-Me. 
     
     
         36 . The compound of  claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2  is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halo, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, and OR a4 . 
     
     
         37 - 59 . (canceled) 
     
     
         60 . A composition comprising a compound of  claim 1 , or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. 
     
     
         61 . A composition comprising a compound of  claim 31 , or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. 
     
     
         62 . A composition comprising a compound of  claim 32 , or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. 
     
     
         63 - 80 . (canceled)