US2023077268A1PendingUtilityA1
Indazoles and azaindazoles as lrrk2 inhibitors
Est. expiryJul 11, 2039(~13 yrs left)· nominal 20-yr term from priority
Inventors:Albert W. GarofaloStéphane De LombaertJacob Bradley SchwarzDaniele AndreottiFabio Maria SabbatiniElena SerraSilvia BernardiMarco MiglioreFederica BudassiClaudia Beato
A61P 25/00C07D 405/12A61K 31/416C07D 405/14C07D 495/04C07D 413/14A61P 25/16C07D 405/04C07D 401/04C07D 401/12A61P 25/28C07D 487/04C07D 231/56C07D 417/14C07D 403/12C07D 401/14C07D 471/04C07D 409/14A61K 31/4439
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Claims
Abstract
The present invention is directed to indazole and azaindazole compounds which are inhibitors of LRRK2 and are useful in the treatment of CNS disorders.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A is Cy 1 , Cy 1 -C 1-4 alkyl-, Cy 1 -C 2-4 alkenyl-, Cy 1 -C 2-4 alkynyl-, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , S(O) 2 NR c R d , or P(O)R c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl of A are each 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, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , S(O) 2 NR c R d , and P(O)R c R d ;
Ring B is phenyl or 5-10 membered heteroaryl, wherein said 5-10 membered heteroaryl comprises 1, 2, or 3 ring-forming heteroatoms independently selected from N, O, and S;
X 2 is N or CR 2 ;
X 3 is N or CR 3 ;
X 4 is N or CR 4 ; wherein not more than two of X 2 , X 3 , and X 4 are simultaneously N;
Cy 1 is selected from C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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 d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ;
each R 1 is independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R 1 are each 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, 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 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;
or two R 1 groups together with the atoms to which they are attached form a C 5-7 cycloalkyl group which 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, 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 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;
R 2 and R 4 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, CN, NO 2 , OR a2 , SR a , 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)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R 2 and R 4 are each 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, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR e2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ;
R 3 is selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-4 cycloalkyl, 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 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and C 3-4 cycloalkyl of R 3 are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, 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 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;
each R a , R b , R c , R d , R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , R d2 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R a , R b , R c , R d , R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , and R d2 is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , and S(O) 2 NR c3 R d3 ;
each R a3 , R b3 , R c3 , and R d3 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy;
each R e , R e1 , R e2 , and R e3 is independently selected from H, C 1-4 alkyl, and CN; and
n is 0, 1, 2, or 3;
wherein when X 2 is CR 2 ; X 3 is CR 3 ; and X 4 is CR 4 , then A is other than —C(═O)OH or —C(═O)OCH 3 ; and
wherein the compound is other than:
2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is Cy 1 , Cy 1 -C 1-4 alkyl-, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl of A are each 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 3-7 cycloalkyl, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; Ring B is phenyl or 5-10 membered heteroaryl, wherein said 5-10 membered heteroaryl comprises 1, 2, or 3 ring-forming heteroatoms independently selected from N, O, and S; X 2 is N or CR 2 ; X 3 is N or CR 3 ; X 4 is N or CR 4 ; wherein not more than two of X 2 , X 3 , and X 4 are simultaneously N; Cy 1 is selected from C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; each R 1 is independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R 1 are each 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, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R a1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; or two R 1 groups together with the atoms to which they are attached form a C 5-7 cycloalkyl group which 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, 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 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; R 2 and R 4 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, CN, NO 2 , OR a2 , SR a , 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)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R 2 and R 4 are each 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, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR e2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ; R 3 is selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-4 cycloalkyl, 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 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and C 3-4 cycloalkyl of R 3 are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, 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 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; each R a , R b , R c , R d , R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , R d2 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R a , R b , R c , R d , R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , and R d2 is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , and S(O) 2 NR c3 R d3 ; each R a3 , R b3 , R c3 , and R d3 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy; each R e , R e1 , R e2 , and R e3 is independently selected from H, C 1-4 alkyl, and CN; and n is 0, 1, 2, or 3; wherein when X 2 is CR 2 ; X 3 is CR 3 ; and X 4 is CR 4 , then A is other than —C(═O)OH or —C(═O)OCH 3 ; and wherein the compound is other than:
3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is Cy 1 , Cy 1 -C 1-4 alkyl-, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl of A are each 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, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; Ring B is phenyl, 5-membered heteroaryl, or 6-membered heteroaryl, wherein said 5- or 6-membered heteroaryl comprises 1, 2, or 3 ring-forming heteroatoms independently selected from N, O, and S; X 2 is N or CR 2 ; X 3 is N or CR 3 ; X 4 is N or CR 4 ; wherein not more than two of X 2 , X 3 , and X 4 are simultaneously N; Cy 1 is selected from C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; each R 1 is independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R 1 are each 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, 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 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ; R 2 and R 4 are each independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R 2 and R 4 are each 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, 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 e2 C(O)OR a2 , NR 2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ; R 3 is selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-4 cycloalkyl, 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 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and C 3-4 cycloalkyl of R 3 are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, 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 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; each R a , R b , R c , R d , R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , R d2 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R a , R b , R c , R d , R a1 , R b1 , R c1 , R d1 , R a2 , R b2 , R c2 , and R d2 is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , and S(O) 2 NR c3 R d3 ; each R a3 , R b3 , R c3 , and R d3 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy; each R e , R e1 , R e2 , and R e3 is independently selected from H, C 1-4 alkyl, and CN; and n is 0, 1, 2, or 3; wherein when X 2 is CR 2 ; X 3 is CR 3 ; and X 4 is CR 4 , then A is other than —C(═O)OH or —C(═O)OCH 3 ; and wherein the compound is other than:
4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein: X 2 is CR 2 ; X 3 is CR 3 ; and X 4 is CR 4 .
5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein: X 2 is N; X 3 is CR 3 ; and X 4 is CR 4 .
6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein: X 2 is CR 2 ; X 3 is N; and X 4 is CR 4 .
7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein: X 2 is CR 2 ; X 3 is CR 3 ; and X 4 is N.
8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein: X 2 is N; X 3 is CR 3 ; and X 4 is N.
9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein: X 2 is N; X 3 is N; and X 4 is CR 4 .
10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein: X 2 is CR 2 ; X 3 is N; and X 4 is N.
11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3 , and R 4 are each H.
12 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is Cy 1 , Cy 1 -C 2-4 alkenyl-, halo, CN, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 haloalkyl, OR a , SR a , NR c C(O)R b , or S(O) 2 R b , wherein said C 1-6 alkyl 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, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
13 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is Cy 1 , halo, C 1-6 alkyl, or NR c C(O)R b , wherein said C 1-6 alkyl 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, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
14 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is Cy 1 , halo, or C 1-6 alkyl 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, 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 , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
15 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is methyl.
16 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is iodo, bromo, chloro, or fluoro.
17 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is iodo.
18 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is Cy 1 .
19 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is C 6-10 aryl or 5-14 membered heteroaryl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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 d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
20 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is phenyl or 5-, 6-, or 8-membered heteroaryl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
21 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is selected from C 3-10 cycloalkyl and 4-14 membered heterocycloalkyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
22 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is selected from C 3-7 cycloalkyl and 4-6 membered heterocycloalkyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
23 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is phenyl, furanyl, pyridyl, pyrazolyl, isoxazolyl, thienyl, benzoxazolyl, thiazolyl, oxazolyl, imidazolyl, oxodihydropyridinyl, isothiazolyl, pyrrolyl, cyclopropyl, pyrimidinyl, triazolyl, oxooxazolyl, azetidinyl, oxetanyl, piperidinyl, dihydrofuranyl, tetrahydropyranyl, cyclobutyl, thieno[2,3-c]pyridinyl, or pyridazinyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
24 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is phenyl, furanyl, pyridyl, pyrazolyl, isoxazolyl, thienyl, benzoxazolyl, thiazolyl, oxazolyl, imidazolyl, oxodihydropyridinyl, isothiazolyl, pyrrolyl, cyclopropyl, or pyrimidinyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR e 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
25 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is phenyl, furanyl, pyridyl, pyrazolyl, isoxazolyl, thienyl, or benzoxazolyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d .
26 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is phenyl, furanyl, pyridyl, pyrazolyl, isoxazolyl, thienyl, benzoxazolyl, thiazolyl, oxazolyl, imidazolyl, oxodihydropyridinyl, isothiazolyl, pyrrolyl, cyclopropyl, or pyrimidinyl.
27 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is phenyl, furanyl, pyridyl, or oxazolyl.
28 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is phenyl, furanyl, or pyridyl.
29 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is furanyl.
30 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is oxazolyl.
31 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is cyclopropyl.
32 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is 5-membered heteroaryl or 6-membered heteroaryl, wherein said 5- or 6-membered heteroaryl comprises 1, 2, or 3 ring-forming heteroatoms independently selected from N, O, and S.
33 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl, pyridyl, pyrimidinyl, thiazolyl, pyrrolyl, furanyl, pyrazolyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazinyl, pyridazinyl, oxodihydropyridinyl, thienopyridyl, indazolyl, dihydro-5H-cyclopenta[c]pyridinyl, or quinolinyl.
34 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl, pyridyl, pyrimidinyl, thiazolyl, pyrrolyl, furanyl, pyrazolyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazinyl, pyridazinyl, oxodihydropyridinyl, thienopyridyl, or indazolyl.
35 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl, pyridyl, pyrimidinyl, thiazolyl, pyrrolyl, furanyl, pyrazolyl, imidazolyl, isothiazolyl, or isoxazolyl.
36 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl, pyridyl, pyrimidinyl, thiazolyl, pyrrolyl, or furanyl.
37 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is pyridyl.
38 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 haloalkyl, and OR a1 .
39 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from H, halo, and C 1-6 alkyl.
40 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from H, F, Cl, Br, I, CH 3 , CH 2 CH 3 , isopropyl, isopropenyl, —CH═CH 2 , C≡CH, CHF 2 , CF 3 , OH, methoxy, OCF 3 , and cyclopropyl.
41 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from H, F, Cl, Br, I, CH 3 , CH 2 CH 3 , isopropyl, isopropenyl, —CH═CH 2 , C≡CH, CHF 2 , CF 3 , OH, methoxy, and OCF 3 .
42 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from H, F, Cl, Br, I, CH 3 , —CH═CH 2 , CHF 2 , CF 3 , OH, and methoxy.
43 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from H, F, Cl, Br, I, and CH 3 .
44 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2.
45 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is Cy 1 ; Ring B is phenyl, pyridyl, pyrimidinyl, thiazolyl, pyrrolyl, furanyl, pyrazolyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazinyl, pyridazinyl, oxodihydropyridinyl, thienopyridyl, indazolyl, dihydro-5H-cyclopenta[c]pyridinyl, or quinolinyl; X 2 is N or CR 2 ; X 3 is CR 3 ; X 4 is CR 4 ; Cy 1 is phenyl, furanyl, pyridyl, pyrazolyl, isoxazolyl, thienyl, benzoxazolyl, thiazolyl, oxazolyl, imidazolyl, oxodihydropyridinyl, isothiazolyl, pyrrolyl, cyclopropyl, pyrimidinyl, triazolyl, oxooxazolyl, azetidinyl, oxetanyl, piperidinyl, dihydrofuranyl, tetrahydropyranyl, cyclobutyl, thieno[2,3-c]pyridinyl, or pyridazinyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; each R 1 is independently selected from H, F, Cl, Br, I, CH 3 , CH 2 CH 3 , isopropyl, isopropenyl, —CH═CH 2 , C≡CH, CHF 2 , CF 3 , OH, methoxy, OCF 3 , and cyclopropyl; R 2 , R 3 , and R 4 are each H; each R a , R b , R c , and R d is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R a , R b , R c , R d , and R a1 is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , and S(O) 2 NR c3 R d3 ; each R a3 , R b3 , R c3 , and R d3 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy; each R e and R e3 is independently selected from H, C 1-4 alkyl, and CN; and n is 0, 1, 2, or 3.
46 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is Cy 1 ; Ring B is phenyl, pyridyl, pyrimidinyl, thiazolyl, pyrrolyl, furanyl, pyrazolyl, imidazolyl, isothiazolyl, or isoxazolyl; X 2 is N or CR 2 ; X 3 is CR 3 ; X 4 is CR 4 ; Cy 1 is phenyl, furanyl, pyridyl, pyrazolyl, isoxazolyl, thienyl, or benzoxazolyl, each optionally substituted by 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 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said substituents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 further substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, 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)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; each R 1 is independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 haloalkyl, and OR a1 ; R 2 , R 3 , and R 4 are each H; each R a , R b , R c , R d , and R a1 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl, C 3-7 cycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl of R a , R b , R c , R d , and R a1 is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , and S(O) 2 NR c3 R d3 ; each R a3 , R b3 , R c3 , and R d3 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy; each R e and R e3 is independently selected from H, C 1-4 alkyl, and CN; and n is 0, 1, 2, or 3.
47 . The compound of claim 1 , selected from:
5-Cyano-3-fluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (1); 2-Bromo-4-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (2); 4-Cyano-2-fluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (3); 4-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-iodobenzamide (4); 2-Chloro-4-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (5); 4-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-(trifluoromethyl)benzamide (6); 4-Cyano-2,6-difluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (7); 6-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-methylnicotinamide (8); 6-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)nicotinamide (9); 4-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2,6-dimethylbenzamide (10); 4-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (11); 4-Cyano-2-methyl-N-(3-methyl-1H-indazol-5-yl)benzamide (12); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-6-methylpicolinamide (13); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (14); 4-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-methoxybenzamide (15); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (16); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-methylbenzamide (17); 4-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-methylbenzamide (18); 3-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-methylbenzamide (19); 2-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)thiazole-5-carboxamide (20); 3-Cyano-N-(3-(pyridin-4-yl)-1H-indazol-5-yl)benzamide (21); 2-Cyano-N-(3-(pyridin-4-yl)-1H-indazol-5-yl)isonicotinamide (22); 4-Cyano-N-(3-(pyridin-4-yl)-1H-indazol-5-yl)picolinamide (23); 5-Cyano-N-(3-(pyridin-4-yl)-1H-indazol-5-yl)nicotinamide (24); 2-Cyano-N-(3-(pyridin-4-yl)-1H-indazol-5-yl)pyrimidine-5-carboxamide (25); 5-Cyano-1,2-dimethyl-N-(3-phenyl-1H-indazol-5-yl)-1H-pyrrole-3-carboxamide (26); 5-Cyano-2-methyl-N-(3-phenyl-1H-indazol-5-yl)furan-3-carboxamide (27); 5-Cyano-N-(3-(3,4-dimethylphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (28); 5-Cyano-N-(3-(furan-2-yl)-1H-indazol-5-yl)-3-methylpicolinamide (29); 5-Cyano-N-(3-(3-(dimethylamino)phenyl)-1H-indazol-5-yl)-3-methylpicolinamide (30); 5-Cyano-3-methyl-N-(3-(pyridin-4-yl)-1H-indazol-5-yl)picolinamide (31); 5-Cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (32); 5-Cyano-3-methyl-N-(3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)picolinamide (33); 5-Cyano-3-methyl-N-(3-(3-(methylsulfonyl)phenyl)-1H-indazol-5-yl)picolinamide (34); 5-Cyano-3-methyl-N-(3-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)picolinamide (35); 5-Cyano-3-methyl-N-(3-(5-methylisoxazol-4-yl)-1H-indazol-5-yl)picolinamide (36); 5-Cyano-3-methyl-N-(3-(5-morpholinopyridin-3-yl)-1H-indazol-5-yl)picolinamide (37); 5-Cyano-N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (38); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-4-hydroxypicolinamide (39); 5-Cyano-3-methyl-N-(3-phenyl-1H-indazol-5-yl)picolinamide (40); 5-Cyano-N-(3-(3-cyanophenyl)-1H-indazol-5-yl)-3-methylpicolinamide (41); 5-Cyano-N-(3-(5-cyanopyridin-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (42); 2-Cyano-1,4-dimethyl-N-(3-phenyl-1H-indazol-5-yl)-1H-imidazole-5-carboxamide (43); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3,6-dimethylpicolinamide (44); 5-Cyano-3-methyl-N-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-indazol-5-yl)picolinamide (45); 5-Cyano-N-(3-(3-fluoro-5-methoxyphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (46); 5-Cyano-N-(3-(4-methoxyphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (47); 5-Cyano-N-(3-(2-methoxypyridin-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (48); 6-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-4-methylnicotinamide (49); 5-Cyano-3-methyl-N-(3-(pyridin-3-yl)-1H-indazol-5-yl)picolinamide (50); 5-Cyano-N-(3-(4-fluoro-3-methylphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (51); 5-Cyano-N-(3-(6-methoxypyridin-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (52); 5-Cyano-N-(3-(3-methoxyphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (53); 5-Cyano-3-methyl-N-(3-(3-(trifluoromethoxy)phenyl)-1H-indazol-5-yl)picolinamide (54); 5-Cyano-3-methyl-N-(3-(6-methylpyridin-3-yl)-1H-indazol-5-yl)picolinamide (55); 5-Cyano-3-methyl-N-(3-(p-tolyl)-1H-indazol-5-yl)picolinamide (56); 5-Cyano-3-methyl-N-(3-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)picolinamide (57); 5-Cyano-3-methyl-N-(3-(m-tolyl)-1H-indazol-5-yl)picolinamide (58); 5-Cyano-3-methyl-N-(3-(3-(trifluoromethyl)phenyl)-1H-indazol-5-yl)picolinamide (59); 5-Cyano-3-methyl-N-(3-(6-(trifluoromethyl)pyridin-3-yl)-1H-indazol-5-yl)picolinamide (60); 5-Cyano-N-(3-(3-fluoro-5-methylphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (61); 5-Cyano-N-(3-(3-cyclopropylphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (62); 5-Cyano-N-(3-(3-fluoro-4-methylphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (63); 5-Cyano-3-(difluoromethyl)-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (64); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)thiazole-2-carboxamide (65); 4-Chloro-5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (66); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (67); 5-Cyano-N-(3-(5-methoxypyridin-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (68); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3-methoxypicolinamide (69); 5-Cyano-3-methyl-N-(3-(4-morpholinophenyl)-1H-indazol-5-yl)picolinamide (70); N-(3-(benzo[d]oxazol-5-yl)-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (71); 3-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-methoxybenzamide (72); 5-Cyano-3-methyl-N-(3-(thiophen-3-yl)-1H-indazol-5-yl)picolinamide (73); 5-Cyano-3-methyl-N-(3-(2-methylpyridin-4-yl)-1H-indazol-5-yl)picolinamide (74); 3-Cyano-2-ethyl-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (75); 5-Cyano-N-(3-(5-cyanofuran-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (76); 3-Cyano-2-fluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (77); 4-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-6-methylpicolinamide (78); 4-Cyano-3-fluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (79); 5-Cyano-N-(3-(furan-3-yl)-7-methyl-1H-indazol-5-yl)-3-methylpicolinamide (80); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-1,3-dimethyl-1H-pyrazole-4-carboxamide (81); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)isoxazole-3-carboxamide (82); 5-Cyano-3-ethyl-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (83); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3-vinylpicolinamide (84); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-4,6-dimethylpicolinamide (85); 2-Chloro-3-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (86); 5-Cyano-N-(3-iodo-1H-indazol-5-yl)-3-methylpicolinamide (87); 3-Cyano-N-(3-(furan-3-yl)-7-methyl-1H-indazol-5-yl)-2-methylbenzamide (88); 2-Bromo-3-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (89); 3-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-1,5-dimethyl-1H-pyrazole-4-carboxamide (90); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)isothiazole-3-carboxamide (91); 3-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-1,4-dimethyl-1H-pyrazole-5-carboxamide (92); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-1,4-dimethyl-1H-pyrazole-3-carboxamide (93); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-4-methylpicolinamide (94); 3-Chloro-5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (95); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-1-methyl-1H-imidazole-2-carboxamide (96); 5-Cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-1-methyl-1H-pyrazole-3-carboxamide (97); 5-Cyano-3-methyl-N-(3-(o-tolyl)-1H-indazol-5-yl)picolinamide (98); 5-Cyano-N-(3-(2-methoxyphenyl)-1H-indazol-5-yl)-3-methylpicolinamide (99); 5-Cyano-N-(3-(furan-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-methylpicolinamide (100), or a pharmaceutically acceptable salt of any of the aforementioned.
48 . The compound of claim 1 , selected from:
5-cyano-N-(3-(isoxazol-5-yl)-1H-indazol-5-yl)-3-methylpicolinamide (101); 5-cyano-3-methyl-N-(3-(5-(morpholinomethyl)thiophen-2-yl)-1H-indazol-5-yl)picolinamide (102); N-(3-(2-bromopyridin-4-yl)-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (103); 2-cyano-1,5-dimethyl-N-(3-phenyl-1H-indazol-5-yl)-1H-imidazole-4-carboxamide (104); 5-cyano-N-(3-(furan-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-methylpicolinamide (105); N-(3-bromo-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (106); 4-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-hydroxybenzamide (107); 5-cyano-3-methyl-N-(3-(4-(morpholine-4-carbonyl)phenyl)-1H-indazol-5-yl)picolinamide (108); 5-cyano-N-(3-(5-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (109); 5-cyano-3-methyl-N-(3-(thiazol-5-yl)-1H-indazol-5-yl)picolinamide (110); 5-cyano-3-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (111); 5-cyano-3-methyl-N-(3-(6-methylpyridin-2-yl)-1H-indazol-5-yl)picolinamide (112); 5-cyano-N-(3-(2-cyanopyridin-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (113); 5-cyano-3-methyl-N-(3-(pyridin-2-yl)-1H-indazol-5-yl)picolinamide (114); 5-cyano-N-(3-(2-((2S,6S)-2,6-dimethylmorpholino)pyridin-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (115); 4-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)thieno[2,3-c]pyridine-7-carboxamide (116); 5-cyano-N-(3-(2-((3R,5S)-3,5-dimethylpiperidin-1-yl)pyridin-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (117); 5-cyano-N-(3-(2-((2S,6R)-2,6-dimethylmorpholino)pyridin-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (118); 5-cyano-N-(3-(3-((2S,6R)-2,6-dimethylmorpholino)phenyl)-1H-indazol-5-yl)-3-methylpicolinamide (119); 3-cyano-2,6-difluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (120); N-(3-(5-chloropyridin-3-yl)-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (121); 5-cyano-2-fluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)benzamide (122); 5-cyano-N-(3-(1,5-dimethyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (123); 4-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-1-methyl-1H-imidazole-2-carboxamide (124); 5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-hydroxybenzamide (125); N-(3-(1H-imidazol-1-yl)-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (126); 6-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (127); 3-cyano-2-fluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)-6-methylbenzamide (128); 5-cyano-3-methyl-N-(3-(2-methyloxazol-5-yl)-1H-indazol-5-yl)picolinamide (129); 5-cyano-N-(3-(4-cyanothiophen-2-yl)-1H-indazol-5-yl)-3-methylpicolinamide (130); 5-cyano-N-(3-(5-cyanothiophen-2-yl)-1H-indazol-5-yl)-3-methylpicolinamide (131); 4-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)pyrimidine-2-carboxamide (132); 5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-4-methyl-1H-pyrazole-3-carboxamide (133); 3-cyano-6-fluoro-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-methylbenzamide (134); N-(3-benzamido-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (135); N-(3-(1H-pyrazol-1-yl)-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (136); 5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3-methyl-1H-pyrazole-4-carboxamide (137); 3-bromo-5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (138); N-(3-(5-chlorothiophen-2-yl)-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (139); 5-cyano-3-methyl-N-(3-(2-methylthiazol-5-yl)-1H-indazol-5-yl)picolinamide (140); 5-cyano-3-methyl-N-(3-(5-methylfuran-2-yl)-1H-indazol-5-yl)picolinamide (141); 5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)quinoline-8-carboxamide (142); 5-cyano-N-(7-fluoro-3-(furan-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (143); 3-chloro-4-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (144); 5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3-methylpyrazine-2-carboxamide (145); 5-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (146); 6-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3-methylpyrazine-2-carboxamide (147); 6-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3-methylpicolinamide (148); 4-cyano-3-ethyl-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (149); 5-cyano-3-ethynyl-N-(3-(furan-3-yl)-1H-indazol-5-yl)picolinamide (150); 5-cyano-3-methyl-N-(3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-indazol-5-yl)picolinamide (151); 5-cyano-3-methyl-N-(3-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-1H-indazol-5-yl)picolinamide (152); 5-cyano-3-methyl-N-(3-(1-methyl-1H-pyrazol-3-yl)-1H-indazol-5-yl)picolinamide (153); 5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-3-hydroxypicolinamide (154); 5-cyano-N-(3-(furan-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-3-methylpicolinamide (155); 5-cyano-3-methyl-N-(3-(thiazol-4-yl)-1H-indazol-5-yl)picolinamide (156); 5-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (157); 5-cyano-3,4-dimethyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (158); 5-cyano-N-(3-(2-methoxypyridin-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (159); 5-cyano-N-(3-(isothiazol-4-yl)-1H-indazol-5-yl)-3-methylpicolinamide (160); 5-cyano-N-(3-(furan-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-3-methylpicolinamide (161); 6-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-4-methylpyridazine-3-carboxamide (162); 3-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2,6-difluorobenzamide (163); 3-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-methoxybenzamide (164); 4-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-fluoro-6-methylbenzamide (165); 2-chloro-3-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)benzamide (166); 3-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-fluorobenzamide (167); 5-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (168); 5-cyano-3,4-dimethyl-N-(3-(1-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)picolinamide (169); 2-cyano-3-fluoro-N-(3-(2-methoxypyridin-4-yl)-1H-indazol-5-yl)isonicotinamide (170); N-(3-(5-chloropyridin-3-yl)-1H-indazol-5-yl)-5-cyano-3,4-dimethylpicolinamide (171); 5-cyano-N-(3-(1-(fluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (172); 3-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-2-(trifluoromethyl)benzamide (173); 5-cyano-3,4-dimethyl-N-(3-(2-methyloxazol-5-yl)-1H-indazol-5-yl)picolinamide (174); 6-chloro-5-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (175); 3-cyano-2-methoxy-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (176); 3-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-fluoro-6-methylbenzamide (177); 5-cyano-N-(3-(2-methoxypyridin-4-yl)-1H-indazol-5-yl)-3-(trifluoromethyl)picolinamide (178); 5-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-4-methylisoxazole-3-carboxamide (179); 3-cyano-N-(3-(furan-3-yl)-1H-indazol-5-yl)-4-methylisoxazole-5-carboxamide (180); 5-cyano-N-(3-(2-isopropyloxazol-5-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (181); 5-cyano-3,4-dimethyl-N-(3-(6-methylpyridin-2-yl)-1H-indazol-5-yl)picolinamide (182); N-(3-(1H-pyrazol-4-yl)-1H-indazol-5-yl)-5-cyano-3,4-dimethylpicolinamide (183); 6-chloro-5-cyano-3,4-dimethyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (184); 5-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3,4,6-trimethylpicolinamide (185); 5-cyano-3,4-dimethyl-N-(3-(1-methyl-1H-pyrrol-3-yl)-1H-indazol-5-yl)picolinamide (186); 5-cyano-3,4-dimethyl-N-(3-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)picolinamide (187); 3-cyano-2,6-difluoro-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (188); 4-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-methoxybenzamide (189); 4-cyano-2-fluoro-6-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (190); 5-cyano-N-(3-(2,6-dimethylpyridin-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (191); 3-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-(trifluoromethyl)benzamide (192); 3-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2,6-dimethylbenzamide (193); 3-cyano-N-(3-(2-methoxypyridin-4-yl)-1H-indazol-5-yl)-1,4-dimethyl-1H-pyrazole-5-carboxamide (194); 3-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-1,4-dimethyl-1H-pyrazole-5-carboxamide (195); 3-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-1,4-dimethyl-1H-pyrazole-5-carboxamide (196); 5-cyano-3,4-dimethyl-N-(3-(4-methyloxazol-2-yl)-1H-indazol-5-yl)picolinamide (197); 5-cyano-3,4-dimethyl-N-(3-(oxazol-2-yl)-1H-indazol-5-yl)picolinamide (198); 3-cyano-2-fluoro-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (199); 4-cyano-2-methoxy-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (200); 4-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-methoxy-6-methylbenzamide (201); 5-cyano-3,4,6-trimethyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (202); 3-cyano-2-fluoro-6-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (203); 5-cyano-N-(3-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (204); 5-cyano-N-(3-(2-ethoxypyridin-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (205); 4-cyano-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-6,7-dihydro-5H-cyclopenta[c]pyridine-1-carboxamide (206); 5-cyano-3,4-dimethyl-N-(3-(5-methyloxazol-2-yl)-1H-indazol-5-yl)picolinamide (207); 4-cyano-2-methoxy-6-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (208); 2-chloro-3-cyano-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (209); 5-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-3,4,6-trimethylpicolinamide (210); 5-cyano-4-methoxy-3-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (211); 3-cyano-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-2-(trifluoromethoxy)benzamide (212); 5-cyano-1,2-dimethyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-6-oxo-1,6-dihydropyridine-3-carboxamide (213); 3-cyano-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-2-(prop-1-en-2-yl)benzamide (214); 5-cyano-3,4-dimethyl-N-(3-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)picolinamide (215); 6-chloro-5-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (216); 5-cyano-N-(3-(1-isopropyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (217); 4-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-6,7-dihydro-5H-cyclopenta[c]pyridine-1-carboxamide (218); 5-cyano-N-(3-(2-methoxy-6-methylpyridin-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (219); 2-chloro-3-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)benzamide (220); 5-cyano-3,4-dimethyl-N-(3-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)picolinamide (221); 5-cyano-3,4,6-trimethyl-N-(3-(thiazol-5-yl)-1H-indazol-5-yl)picolinamide (222); 5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-3,4-dimethylpicolinamide (223); 5-cyano-1-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-6-oxo-1,6-dihydropyridine-3-carboxamide (224); 3-cyano-2-isopropyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (225); 5-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-4-methoxy-3-methylpicolinamide (226); 5-cyano-3,4-dimethyl-N-(3-(thiazol-5-yl)-1H-indazol-5-yl)picolinamide (227); 4-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-3-methoxypicolinamide (228); 5-cyano-3,4-dimethyl-N-(3-(3-methylisoxazol-5-yl)-1H-indazol-5-yl)picolinamide (229); 5-cyano-3,4-dimethyl-N-(3-(pyrimidin-4-yl)-1H-indazol-5-yl)picolinamide (230); 3-cyano-2-ethyl-6-fluoro-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (231); 2-cyano-3-ethyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)isonicotinamide (232); (E)-5-cyano-N-(3-(2-cyclopropylvinyl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (233); 3-cyano-2-methoxy-6-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)benzamide (234); 5-cyano-3-methyl-N-(3-(3-methylisoxazol-5-yl)-1H-indazol-5-yl)picolinamide (235); 3-cyano-2-fluoro-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-6-methylbenzamide (236); 5-cyano-3,4-dimethyl-N-(3-(2-methylpyrimidin-4-yl)-1H-indazol-5-yl)picolinamide (237); 5-cyano-3,4-dimethyl-N-(3-(oxazol-5-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)picolinamide (238); and 3-cyano-1,4-dimethyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-1H-pyrazole-5-carboxamide (239), or a pharmaceutically acceptable salt of any of the aforementioned.
49 . The compound of claim 1 , selected from:
5-cyano-3,4-dimethyl-N-(3-(1-methyl-1H-1,2,3-triazol-4-yl)-1H-indazol-5-yl)picolinamide (240); 5-cyano-3-methyl-N-(3-(1-methyl-1H-1,2,3-triazol-4-yl)-1H-indazol-5-yl)picolinamide (241); 5-cyano-3-methyl-N-(3-(2-oxooxazol-3(2H)-yl)-1H-indazol-5-yl)picolinamide (242); 5-cyano-3,4-dimethyl-N-(3-(2-methylprop-1-en-1-yl)-1H-indazol-5-yl)picolinamide (243); (E)-5-cyano-3,4-dimethyl-N-(3-styryl-1H-indazol-5-yl)picolinamide (244); (E)-5-cyano-3,4-dimethyl-N-(3-(prop-1-en-1-yl)-1H-indazol-5-yl)picolinamide (245); 4-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-1,3-dimethyl-1H-pyrrole-2-carboxamide (246); 4-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)-1-methyl-1H-pyrrole-2-carboxamide (247); (E)-5-cyano-3,4-dimethyl-N-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-5-yl)picolinamide (248); 5-cyano-4-methoxy-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (249); 5-cyano-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-3-(prop-1-en-2-yl)picolinamide (250); 5-cyano-3-isopropyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (251); 5-cyano-3,4-dimethyl-N-(3-((1R)-2-phenylcyclopropyl)-1H-indazol-5-yl)picolinamide (252); N-(3-(azetidin-1-yl)-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (253); 5-cyano-N-(3-(3,3-difluoroazetidin-1-yl)-1H-indazol-5-yl)-3-methylpicolinamide (254); N-(3-(benzyloxy)-1H-indazol-5-yl)-5-cyano-3-methylpicolinamide (255); 5-cyano-3-methyl-N-(3-(oxetan-3-yl)-1H-indazol-5-yl)picolinamide (256); 5-cyano-N-(3-(2,2-dimethylcyclopropyl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (257); 5-cyano-4-methoxy-6-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (258); tert-butyl 4-((5-(5-cyano-3,4-dimethylpicolinamido)-1H-indazol-3-yl)methylene)piperidine-1-carboxylate (259); 5-cyano-3,4-dimethyl-N-(3-(piperidin-4-ylidenemethyl)-1H-indazol-5-yl)picolinamide (260); (Z)-5-cyano-N-(3-((dihydrofuran-3(2H)-ylidene)methyl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (261); 5-cyano-3,4-dimethyl-N-(3-((tetrahydro-4H-pyran-4-ylidene)methyl)-1H-indazol-5-yl)picolinamide (262); 5-cyano-3,4-dimethyl-N-(3-(oxetan-3-ylidenemethyl)-1H-indazol-5-yl)picolinamide (263); 5-cyano-N-(3-(methoxymethyl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (264); 5-cyano-3,4-dimethyl-N-(3-(2-(trifluoromethyl)cyclopropyl)-1H-indazol-5-yl)picolinamide (265); (E)-5-cyano-3,4-dimethyl-N-(3-(3,3,3-trifluoroprop-1-en-1-yl)-1H-indazol-5-yl)picolinamide (266); 5-cyano-3,4-dimethyl-N-(3-(prop-1-en-2-yl)-1H-indazol-5-yl)picolinamide (267); 5-cyano-3,4-dimethyl-N-(3-(1-methylcyclopropyl)-1H-indazol-5-yl)picolinamide (268); 5-cyano-N-(3-(1-methoxyethyl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (269); 6-chloro-5-cyano-N-(3-isopropyl-1H-indazol-5-yl)-3,4-dimethylpicolinamide (270); 6-chloro-5-cyano-N-(3-ethyl-1H-indazol-5-yl)-3,4-dimethylpicolinamide (271); 5-cyano-3-methyl-N-(3-(pyridazin-4-yl)-1H-indazol-5-yl)picolinamide (272); 5-cyano-3-methyl-N-(3-(6-methylpyridazin-4-yl)-1H-indazol-5-yl)picolinamide (273); 3-cyano-N-(3-methyl-1H-indazol-5-yl)-2-(prop-1-en-2-yl)benzamide (274); 3-chloro-5-cyano-4,6-dimethyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (275); 5-cyano-N-(3-(cyclobutylidenemethyl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (276); 5-cyano-3,4-dimethyl-N-(3-(2-morpholinopyridin-4-yl)-1H-indazol-5-yl)picolinamide (277); 6-chloro-5-cyano-3,4-dimethyl-N-(3-(2-morpholinopyridin-4-yl)-1H-indazol-5-yl)picolinamide (278); 5-cyano-N-(3-(2-ethylpyridin-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (279); 5-cyano-3,4-dimethyl-N-(3-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)-1H-indazol-5-yl)picolinamide (280); (E)-5-cyano-3,4-dimethyl-N-(3-(2-(pyridin-4-yl)vinyl)-1H-indazol-5-yl)picolinamide (281); (E)-6-chloro-5-cyano-3,4-dimethyl-N-(3-(prop-1-en-1-yl)-1H-indazol-5-yl)picolinamide (282); 3-chloro-5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-4,6-dimethylpicolinamide (283); 5-cyano-N-(3-ethyl-1H-indazol-5-yl)-3-methyl-4-(trifluoromethyl)picolinamide (284); 5-cyano-N-(3-methoxy-1H-indazol-5-yl)-3-methyl-4-(trifluoromethyl)picolinamide (285); 5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-3-methyl-4-(trifluoromethyl)picolinamide (286); 5-cyano-N-(3-methoxy-1H-indazol-5-yl)-3,4,6-trimethylpicolinamide (287); 5-cyano-3-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-6-(trifluoromethyl)picolinamide (288); 5-cyano-3-methyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)-4-(trifluoromethyl)picolinamide (289); 6-chloro-5-cyano-N-(3-cyano-1H-indazol-5-yl)-3,4-dimethylpicolinamide (290); 6-chloro-5-cyano-N-(3-(difluoromethyl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (291); 5-cyano-N-(3-(difluoromethyl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (292); 6-chloro-5-cyano-3,4-dimethyl-N-(3-(trifluoromethyl)-1H-indazol-5-yl)picolinamide (293); 5-cyano-3-isopropyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (294); 3-cyano-2-isopropyl-N-(3-methyl-1H-indazol-5-yl)benzamide (295); 6-chloro-5-cyano-3,4-dimethyl-N-(3-(methylsulfonyl)-1H-indazol-5-yl)picolinamide (296); 5-cyano-3,4-dimethyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (297); 6-chloro-5-cyano-3,4-dimethyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (298); 3-cyano-2-methoxy-6-methyl-N-(3-methyl-1H-indazol-5-yl)benzamide (299); N-(3-bromo-1H-indazol-5-yl)-5-cyano-3,4-dimethylpicolinamide (300); N-(3-chloro-1H-indazol-5-yl)-5-cyano-3,4-dimethylpicolinamide (301); 6-bromo-5-cyano-3,4-dimethyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (302); 6-chloro-5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-3,4-dimethylpicolinamide (303); 5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-6-methoxy-3,4-dimethylpicolinamide (304); 5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-3,4,6-trimethylpicolinamide (305); 4-chloro-5-cyano-3-methyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (306); 6-chloro-5-cyano-3-methyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (307); 6-chloro-5-cyano-N-(3-methoxy-1H-indazol-5-yl)-3,4-dimethylpicolinamide (308); 3-chloro-5-cyano-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)picolinamide (309); 5-cyano-3-cyclopropyl-N-(3-(isoxazol-4-yl)-1H-indazol-5-yl)picolinamide (310); 5-cyano-3-cyclopropyl-N-(3-(3-methoxyphenyl)-1H-indazol-5-yl)picolinamide (311); 5-cyano-3-cyclopropyl-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (312); 5-cyano-N-(3-methyl-1H-indazol-5-yl)-3-(prop-1-en-2-yl)picolinamide (313); 5-cyano-N-(7-fluoro-1H-indazol-5-yl)-3,4-dimethylpicolinamide (314); 5-cyano-N-(3-fluoro-1H-indazol-5-yl)-3,4-dimethylpicolinamide (315); 3-cyano-6-fluoro-2-methyl-N-(3-methyl-1H-indazol-5-yl)benzamide (316); 6-chloro-5-cyano-3,4-dimethyl-N-(3-(methylthio)-1H-indazol-5-yl)picolinamide (317); 3-chloro-5-cyano-N-(3-(oxazol-5-yl)-1H-indazol-5-yl)picolinamide (318); 5-cyano-N-(3-(3-(dimethylphosphoryl)phenyl)-1H-indazol-5-yl)-3-methylpicolinamide (319); 6-chloro-N-(3-chloro-1H-indazol-5-yl)-5-cyano-3,4-dimethylpicolinamide (320); N-(3-chloro-1H-indazol-5-yl)-5-cyano-6-methoxy-3,4-dimethylpicolinamide (321); 5-cyano-6-methoxy-3,4-dimethyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (322); 5-cyano-3-methyl-N-(3-(3-(piperidin-1-yl)propyl)-1H-indazol-5-yl)picolinamide (323); N-(3-bromo-1H-indazol-5-yl)-6-chloro-5-cyano-3,4-dimethylpicolinamide (324); 5-cyano-3,4,6-trimethyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (325); 3-chloro-5-cyano-4-methyl-N-(3-methyl-1H-indazol-5-yl)picolinamide (326); 5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-6-(difluoromethyl)-3,4-dimethylpicolinamide (327); 5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-3,4-dimethyl-6-(trifluoromethyl)picolinamide (328); 6-bromo-5-cyano-N-(3-methoxy-1H-indazol-5-yl)-3,4-dimethylpicolinamide (329); 6-bromo-5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-3,4-dimethylpicolinamide (330); 3,6-dichloro-5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-4-methylpicolinamide (331); 5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-3,4-dimethyl-6-vinylpicolinamide (332); 5-cyano-N-(3-cyclopropyl-1H-indazol-5-yl)-6-ethyl-3,4-dimethylpicolinamide (333); 5-cyano-6-cyclopropyl-N-(3-cyclopropyl-1H-indazol-5-yl)-3,4-dimethylpicolinamide (334); and 5-cyano-N-(3-(1-cyclopropyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)-3,4-dimethylpicolinamide (335); or a pharmaceutically acceptable salt of any of the aforementioned.
50 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
51 . A method of inhibiting LRRK2 activity, said method comprising contacting a compound of claim 1 or a pharmaceutically acceptable salt thereof with LRRK2.
52 . The method of claim 51 , wherein the LRRK2 is characterized by a G2019S mutation.
53 . The method of claim 51 , wherein the contacting comprises administering the compound to a patient.
54 . A method of treating a disease or disorder associated with elevated expression or activity of LRRK2, or a functional variant thereof, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
55 . The method of claim 54 , wherein the LRRK2 is characterized by a G2019S mutation.
56 . A method for treating a neurodegenerative disease in a patient, said method comprising: administering to the patient a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.
57 . The method of claim 56 , wherein said neurodegenerative disease is selected from Parkinson's disease, Parkinson disease with dementia, Parkinson's associated risksyndrome, dementia with Lewy bodies, Lewy body variant of Alzheimer's disease, combined Parkinson's disease and Alzheimer's disease, multiple system atrophy, striatonigral degeneration, olivopontocerebellar atrophy, and Shy-Drager syndrome.
58 . The method of claim 56 , wherein said neurodegenerative disease is Parkinson's disease.
59 . The method of claim 58 , wherein the Parkinson's disease is characterized by a G2019S mutation in LRRK2.Join the waitlist — get patent alerts
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