N-HYDROXYAMIDINOHETEROCYCLES AS MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE

1 . A compound of Formula I:

or pharmaceutically acceptable salt thereof, wherein:

W is O, S, or NR 1 ;

U is N or CR 3 ;

X is N or CR 4 ;

Q is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, pentahalosulfanyl, Cy 4 , —(C 1-4 alkyl)-Cy 4 , CN, NO 2 , OR a4 , —(C 1-4 alkyl)-OR a4 , SR a4 , —(C 1-4 alkyl)-SR a4 , C(O)R b4 , —(C 1-4 alkyl)-C(O)R b4 , C(O)NR c4 R d4 , —(C 1-4 alkyl)-C(O)NR c4 R d4 , C(O)OR a4 , —(C 1-4 alkyl)-C(O)OR a4 , OC(O)R b4 , —(C 1-4 alkyl)-OC(O)R b4 , OC(O)NR c4 R d4 , —(C 1-4 alkyl)-OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , —(C 1-4 alkyl) NR c4 COR b4 , NR c4 C(O)NR c4 R d4 , —(C 1-4 alkyl)-NR c4 C(O)NR c4 R d4 , NR c4 C(O)OR a4 , —(C 1-4 alkyl)-NR c4 C(O)OR a4 , C(═NR i4 )NR c4 R d4 , NR c4 C(═NR i4 )NR c4 R d4 , P(R f4 ) 2 , P(OR e4 ) 2 , P(O)R e4 R f4 , P(O)OR e4 OR f4 , S(O)R b4 , —(C 1-4 alkyl)-S(O)R b4 , S(O)NR c4 R d4 , —(C 1-4 alkyl)-S(O)NR c4 R d4 , S(O) 2 R b4 , —(C 1-4 alkyl)-S(O) 2 R b4 , NR c4 S(O) 2 R b4 , —(C 1-4 alkyl)-NR c4 S(O) 2 R b4 , S(O) 2 NR c4 R d4 , and —(C 1-4 alkyl)-S(O) 2 NR c4 R d4 ;

R 1 is H, C 1-10 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl;

R 2 is halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, pentahalosulfanyl, Cy 3 , 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR i3 )NR c3 R d3 , NR c3 C(═NR i3 )NR c3 R d3 , P(R f3 ) 2 , P(OR e3 ) 2 , P(O)R e3 R f3 , P(O)OR e3 OR f3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , or S(O) 2 NR c3 R d3 ; 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 substituents independently selected from halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 haloalkyl, C 1-10 hydroxyalkyl, C 1-10 cyanoalkyl, pentahalosulfanyl, Cy 3 , 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR i3 )NR c3 R d3 , NR c3 C(═NR i3 )NR c3 R d3 , P(R f3 ) 2 , P(OR e3 ) 2 , P(O)R e3 R f3 , P(O)OR e3 OR f3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;

R 3 and R 4 are independently selected from H, halo, C 1-4 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl;

R 5 is H, C(O)R 6 , C(O)OR 7 , or C(O)NR 8 NR 9 ;

R 6 and R 7 are independently selected from H, C 1-8 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, each optionally substituted by 1, 2, 3 substituents independently selected from halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl;

R 8 and R 9 are independently selected from H, C 1-8 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, each optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl;

or R 1 and R 3 together with the atoms to which they are attached form a heteroaryl or a 4-20 membered heterocycloalkyl ring, wherein said heteroaryl or 4-20 membered heterocycloalkyl ring 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, CN, NO 2 , OR a3 , 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 , C(═NR i )NR c R d , NR c C(═NR i )NR c R d , P(R f ) 2 , P(OR e ) 2 , P(O)R e R f , P(O)OR e OR f , 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 substituents independently selected from Cy, 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 , C(═NR i )NR c R d , NR c C(═NR i )NR c R d , P(R f ) 2 , P(OR e ) 2 , P(O)R e R f , P(O)OR e OR f , 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 ;

or R 2 and R 3 together with the atoms to which they are attached form an aryl, cycloalkyl, heteroaryl, or 4-20 membered heterocycloalkyl ring, wherein said aryl, cycloalkyl, heteroaryl, or 4-20 membered heterocycloalkyl ring 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 1 , 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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, C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 1 , 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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 ;

or R 2 and R 4 together with the atoms to which they are attached form an aryl, cycloalkyl, heteroaryl or 4-20 membered heterocycloalkyl ring, wherein said aryl, cycloalkyl, heteroaryl, or 4-20 membered heterocycloalkyl ring 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 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 , C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , 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 , wherein said C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 2 , 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 , C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , 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 a3 and R a4 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Cy 5 , and Cy 5 —(C 1-6 alkyl)-, wherein said C 1-6 alkyl, 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 5 , 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 , C(═NR i5 )NR c5 R d5 , NR c5 C(═NR i5 )NR c5 R d5 , P(R f5 ) 2 , P(OR e5 ) 2 , P(O)R e5 R f5 , P(O)OR e5 OR f5 , 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 b3 and R b4 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Cy 5 , and Cy 5 —(C 1-6 alkyl)-, wherein said C 1-6 alkyl, 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 5 , 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 , C(═NR i5 )NR c5 R d5 , NR c5 C(═NR i5 )NR c5 R d5 , P(R f5 ) 2 , P(OR e5 ) 2 , P(O)R e5 R f5 P(O)OR e5 OR f5 , S(O) 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 c3 and R c4 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R b5 , C(O)NR c5 R d5 , C(═NR i5 )NR c5 R d5 , Cy 5 , and Cy 5 —(C 1-6 alkyl)-, wherein said C 1-6 alkyl, 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 5 , 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 , C(═NR i5 )NR c5 R d5 , NR c5 C(═NR i5 )NR c5 R d5 , P(R f5 ) 2 , P(OR e5 ) 2 , P(O)R e5 R f5 , P(O)OR e5 OR f5 , 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 d3 and R d4 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R b5 , C(O)NR c5 R d5 , C(═NR i5 )NR c5 R d5 , Cy 5 and Cy 5 —(C 1-6 alkyl)-, wherein said C 1-6 alkyl, 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 5 , 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 , C(═NR i5 )NR c5 R d5 , NR c5 C(═NR i5 )NR c5 R d5 , P(R f5 ) 2 , P(OR e5 ) 2 , P(O)R e5 R f5 , P(O)OR e5 OR f5 , 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 c3 and R d3 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heteroaryl or heterocycloalkyl group, 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 5 , 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 , C(═NR i5 )NR c5 R d5 , NR c5 C(═NR i5 )NR c5 R d5 , P(R f5 ) 2 , P(OR e5 ) 2 , P(O)R e5 R f5 , P(O)OR e5 OR f5 , 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 c4 and R d4 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heteroaryl or heterocycloalkyl group, 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 5 , CN, NO 2 , OR 35 , 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 , C(═NR i5 )NR c5 R d5 , NR c5 C(═NR i5 )NR c5 R d5 , P(R f5 ) 2 , P(OR e5 ) 2 , P(O)R e5 R f5 , P(O)OR e5 OR f5 , S(O)R b5 , S(O)NR c5 R b5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ;

Cy, Cy 1 , Cy 2 , Cy 3 , Cy 4 , Cy 5 are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 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, pentahalosulfanyl, 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 , C(═NR i6 )NR c6 R d6 , NR c6 C(═NR i6 )NR c6 R d6 , P(R f6 ) 2 , P(OR e6 ) 2 , P(O)R e6 R f6 , P(O)OR e6 OR f6 , 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 , R a1 , R a2 , R a5 , and R a6 are independently selected from H, C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;

R b , R b1 , R b2 , R b5 , and R b6 are independently selected from H, C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;

R c , R c1 , R c2 , R c5 , and R c6 are independently selected from H, C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;

R d , R d1 , R d2 , R d5 , and R d6 are independently selected from H, C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;

R e , R e1 , R e2 , R e5 , and R e6 are independently selected from H, C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;

R f , R f1 , R f2 , R f3 , R f4 , R f5 , and R f6 are independently selected from H, C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; and

R i , R i1 , R i2 , R i3 , R i4 , R i5 , and R i6 are independently selected from H, C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-10 haloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;

with the proviso that when the ring containing U, W, and X is oxadiazole, then Q is other than C 1-6 alkyl substituted with NR c4 R d4 .

2 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein W is O.

3 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein U is N.

4 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein X is CR 4 .

5 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein W is S.

6 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein U is CR 3 .

7 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein W is O and U is N.

8 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein W is S and U is CR 3 .

9 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein W is O and U is CR 3 .

10 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Q is aryl or 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 4 , —(C 1-4 alkyl)-Cy 4 , CN, NO 2 , OR a4 , —(C 1-4 alkyl)-OR a4 , SR a4 , —(C 1-4 alkyl)-SR a4 , C(O)R b4 , —(C 1-4 alkyl)-C(O)R b4 , C(O)NR c4 R d4 , —(C 1-4 alkyl)-C(O)NR c4 R d4 , C(O)OR a4 , —(C 1-4 alkyl)-C(O)OR a4 , OC(O)R b4 , —(C 1-4 alkyl)-OC(O)R b4 , OC(O)NR c4 R d4 , —(C 1-4 alkyl)-OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , —(C 1-4 alkyl)-NR c4 COR b4 , NR c4 C(O)NR c4 R d4 , —(C 1-4 alkyl)-NR c4 C(O)NR c4 R d4 , NR c4 C(O)OR a4 , —(C 1-4 alkyl)-NR c4 C(O)OR a4 , C(═NR i4 )NR c4 R d4 , NR c4 C(═NR i4 )NR c4 R d4 , P(R f4 ) 2 , P(OR e4 ) 2 , P(O)R e4 R f4 , P(O)OR e4 R f4 , S(O)R b4 , —(C 1-4 alkyl)-S(O)R b4 , S(O)NR c4 R d4 , —(C 1-4 alkyl)-S(O)NR c4 R d4 , S(O) 2 R b4 , —(C 1-4 alkyl)-S(O) 2 R b4 , NR c4 S(O) 2 R b4 , —(C 1-4 alkyl)-NR c4 S(O) 2 R b4 , S(O) 2 NR c4 R d4 , and —(C 1-4 alkyl)-S(O) 2 NR c4 R d4 .

11 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Q is aryl 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 4 , —(C 1-4 alkyl)-Cy 4 , CN, NO 2 , OR a4 , —(C 1-4 alkyl)-OR a4 , SR a4 , —(C 1-4 alkyl)-SR a4 , C(O)R b4 , —(C 1-4 alkyl)-C(O)R b4 , C(O)NR c4 R d4 , —(C 1-4 alkyl)-C(O)NR c4 R d4 , C(O)OR a4 , —(C 1-4 alkyl)-C(O)OR a4 , OC(O)R b4 , —(C 1-4 alkyl)-OC(O)R b4 , OC(O)NR c4 R d4 , —(C 1-4 alkyl)-OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , —(C 1-4 alkyl)-NR c4 COR b4 , NR c4 C(O)NR c4 R d4 , —(C 1-4 alkyl)-NR c4 C(O)NR c4 R d4 , NR c4 C(O)OR a4 , —(C 1-4 alkyl)-NR c4 C(O)OR a4 , C(═NR i4 )NR c4 R d4 , NR c4 C(═NR i4 )NR c4 R d4 , P(R f4 ) 2 , P(OR e4 ) 2 , P(O)R e4 R f4 , P(O)OR e4 OR f4 , S(O)R b4 , —(C 1-4 alkyl)-S(O)R b4 , S(O)NR c4 R d4 , (C 1-4 alkyl)-S(O)NR c4 R d4 , S(O) 2 R b4 , —(C 1-4 alkyl)-S(O) 2 R b4 , NR c4 S(O) 2 R b4 , —(C 1-4 alkyl)-NR c4 S(O) 2 R b4 , S(O) 2 NR c4 R d4 , and —(C 1-4 alkyl)-S(O) 2 NR c4 R d4 .

12 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Q is phenyl 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, 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)NR c4 R d4 , NR c4 C(O)OR a4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , NR c4 S(O) 2 R b4 , and S(O) 2 NR c4 R d4 .

13 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Q is phenyl optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, and CN.

14 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Q is phenyl optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo and CN.

15 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Q is C 1-6 alkyl 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, pentahalosulfanyl, Cy 4 , —(C 1-4 alkyl)-Cy 4 , CN, NO 2 , OR a4 , —(C 1-4 alkyl)-OR a4 , SR a4 , —(C 1-4 alkyl)-SR a4 , C(O)R b4 , —(C 1-4 alkyl)-C(O)R b4 , C(O)NR c4 R d4 , —(C 1-4 alkyl)-C(O)NR c4 R d4 , C(O)OR a4 , —(C 1-4 alkyl)-C(O)OR a4 , OC(O)R b4 , —(C 1-4 alkyl)-OC(O)R b4 , OC(O)NR c4 R d4 , —(C 1-4 alkyl)-OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , —(C 1-4 alkyl)-NR c4 COR b4 , NR c4 C(O)NR c4 R d4 , —(C 1-4 alkyl)-NR c4 C(O)NR c4 R d4 , NR c4 C(O)OR b4 , —(C 1-4 alkyl)-NR c4 C(O)OR a4 , C(═NR i4 )NR c4 R d4 , NR c4 C(═NR i4 )NR c4 R d4 , P(R f4 ) 2 , P(OR e4 ) 2 , P(O)R e4 R f4 , P(O)OR f4 , S(O)R b4 , —(C 1-14 alkyl)-S(O)R b4 , S(O)NR c4 R d4 , —(C 1-14 alkyl)-S(O)NR c4 R d4 , S(O) 2 R e4 , —(C 1-4 alkyl)-S(O) 2 R b4 , NR c4 S(O) 2 R b4 , —(C 1-4 alkyl)-NR c4 S(O) 2 R b4 , S(O) 2 NR c4 R d4 , and —(C 1-4 alkyl)-S(O) 2 NR c4 R d4 .

16 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Q is C 1-6 alkyl substituted by Cy 4 .

17 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Q is C 1-6 alkyl substituted by phenyl, wherein said phenyl is substituted by 1, 2, or 3 substituents independently selected from halo and C 1-4 alkyl.

18 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 3 , 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)NR c3 R d3 , NR c3 C(O)OR a3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , or S(O) 2 NR c3 R d3 ; 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 substituents independently selected from halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 haloalkyl, C 1-10 hydroxyalkyl, C 1-10 cyanoalkyl, Cy 3 , CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR c3 C(O)R b3 , C(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 i3 )NR c3 R d3 , NR c3 C(═NR i3 )NR c3 R d3 , P(R f3 ) 2 , P(OR e3 ) 2 , P(O)R e3 R f3 , P(O)OR e3 OR f3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , and S(O) 2 NR c3 R d3 .

19 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 3 , 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)NR c3 R d3 , NR c3 C(O)OR a3 ; 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 substituents independently selected from halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 haloalkyl, C 1-10 hydroxyalkyl, C 1-10 cyanoalkyl, Cy 3 , 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR i3 )NR c3 R d3 , NR c3 C(═NR i3 )NR c3 R d3 , P(R f3 ) 2 , P(OR e3 ) 2 , P(O)R e3 R f3 , P(O)OR e3 OR f3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , NR c3 S(O) 2 R b3 , and S(O) 2 NR c3 R d3 .

20 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 3 , 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 ; 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 substituents independently selected from halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 haloalkyl, C 1-10 hydroxyalkyl, C 1-10 cyanoalkyl, Cy 3 , 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)NR b3 , NR c3 C(O)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR i3 )NR c3 R d3 , NR c3 C(═NR i3 )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 , and S(O) 2 NR c3 R d3 .

21 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is halo, C 1-10 alkyl, Cy 3 , OR a3 , wherein said C 1-10 alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 haloalkyl, C 1-10 hydroxyalkyl, C 1-10 cyanoalkyl, Cy 3 , 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)NR c3 R d3 , NR c3 C(O)OR a3 , C(═NR i3 )NR c3 R d3 , NR c3 C(═NR i3 )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 , and S(O) 2 NR c3 R d3 .

22 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is halo, C 1-10 alkyl, OR a3 , aryl, heteroaryl, or heterocycloalkyl, wherein said C 1-10 alkyl, aryl, heteroaryl, or heterocycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-10 alkyl, C 1-6 haloalkyl, OR a3 , and NR c3 R d3 .

23 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is halo.

24 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is C 1-10 alkyl.

25 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is NR c3 R d3 .

26 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 is NH 2 .

27 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 3 together with the atoms to which they are attached form an aryl, heteroaryl, or 4-20 membered heterocycloalkyl ring, 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 1 , 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 1 , 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 , C(NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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 .

28 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 3 together with the atoms to which they are attached form an aryl or heteroaryl, 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 1 , 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 1 , 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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 .

29 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 3 together with the atoms to which they are attached form an aryl 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 1 , 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 1 , 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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 .

30 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 3 together with the atoms to which they are attached form an aryl 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 1 , 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 P(R f1 ) 2 , P(OR e1 ) 2 , P(O)R e1 R f1 , P(O)OR e1 OR f1 , 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 .

31 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 3 together with the atoms to which they are attached form an aryl 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, 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , 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 .

32 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 3 together with the atoms to which they are attached form an aryl 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, CN, NO 2 , OR a1 , and SR a1 .

33 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 3 together with the atoms to which they are attached form a phenyl group.

34 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 4 together with the atoms to which they are attached form an aryl, heteroaryl or 4-20 membered heterocycloalkyl ring, 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 2 , 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 C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , 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 , wherein said C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 2 , CN, NO 2 , OR a2 , SR 2 , 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 , C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , P(R f2 ), P(OR e1 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , 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 .

35 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 4 together with the atoms to which they are attached form an aryl or heteroaryl, 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 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 2 , 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 , C(═NR i2 )NR c2 R d2 NR c2 C(═NR i2 )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , 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 , wherein said C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 2 , 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 , C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , 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 .

36 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 4 together with the atoms to which they are attached form an aryl 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 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 , C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , 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 , wherein said C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 2 , 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 , C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , 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 .

37 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 4 together with the atoms to which they are attached form an aryl 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 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 , C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , 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 , wherein said C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 2 , CN, NO 2 , OR a2 , SR 2 , 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 , C(═NR i2 )NR c2 R d2 , NR c2 C(═NR i2 )NR c2 R d2 , 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 .

38 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 4 together with the atoms to which they are attached form an aryl 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 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 , wherein said C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 2 , 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 .

39 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 4 together with the atoms to which they are attached form an aryl 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, 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 , C(═NR i1 )NR c1 R d1 , NR c1 C(═NR i1 )NR c1 R d1 , 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 .

40 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 4 together with the atoms to which they are attached form an aryl optionally substituted 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, CN, NO 2 , OR a1 , and SR a1 .

41 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 2 and R 4 together with the atoms to which they are attached form a phenyl group.

42 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 5 is H.

43 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, having Formula II:

44 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, having Formula III:

45 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, having Formula IV:

46 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, having Formula V:

47 . The compound of claim 1 selected from:

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-(3-morpholin-1-ylpropoxy)isoxazole-5-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-(3-(pyrrolidin-1-yl)propoxy)isoxazole-5-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-morpholin-1-ylisoxazole-5-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-phenylisoxazole-5-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-(4-methoxyphenyl)isoxazole-5-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-methoxyisoxazole-5-carboximidamide;

3-bromo-N-(3-bromophenyl)-N′-hydroxyisoxazole-5-carboximidamide;

3-bromo-N-(3-chloro-4-fluorophenyl)-N′-hydroxyisoxazole-5-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-(3-(4-methylpiperazin-1-yl)propoxy)isoxazole-5-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-methylisoxazole-5-carboximidamide;

4-chloro-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-3-methylisoxazole-5-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4,5-dimethylfuran-2-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-2,1-benzisoxazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1-benzothiophene-2-carboximidamide;

3-bromo-N-(3-chlorobenzyl)-N′-hydroxyisoxazole-5-carboximidamide;

3-bromo-N-(3-chloro-2-methylbenzyl)-N′-hydroxyisoxazole-5-carboximidamide;

3-bromo-N-(5-chloro-2-methylbenzyl)-N′-hydroxyisoxazole-5-carboximidamide;

3-bromo-N′-hydroxy-N-(2-methylbenzyl)isoxazole-5-carboximidamide;

N′-hydroxy-3-methyl-N-(2-methylbenzyl)isoxazole-5-carboximidamide;

N′-hydroxy-N-(2-methylbenzyl)-2,1-benzisoxazole-3-carboximidamide;

3-Amino-N-(5-chloro-2-methylbenzyl)-N′-hydroxyisoxazole-5-carboximidamide;

N-[5-[(5-chloro-2-methylbenzyl)amino](hydroxyimino)methyl]isoxazol-3-ylacetamide;

N-(5-chloro-2-methylbenzyl)-N′-hydroxy-3-[(2-methoxyethyl)amino] isoxazole-5-carboximidamide; and

3-amino-N-(3-bromo-4-fluorophenyl)-N′-hydroxyisoxazole-5-carboximidamide,

or pharmaceutically acceptable salt thereof.

48 . A composition comprising a compound of claim 1 , or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

49 . A method of modulating activity of indoleamine 2,3-dioxygenase comprising contacting said indoleamine 2,3-dioxygenase with a compound of claim 1 , or pharmaceutically acceptable salt thereof.

50 . The method of claim 49 wherein said modulating is inhibiting.

51 . A method of inhibiting immunosuppression in a patient comprising administering to said patient an effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof.

52 . A method of treating cancer, viral infections, depression, a neurodegenerative disorder, trauma, age-related cataracts, organ transplant rejection, or an autoimmune disease in a patient comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof.

53 . The method of claim 52 further comprising administering an anti-viral agent, a chemotherapeutic, an immunosuppressant, radiation, an anti-tumor vaccine, an antiviral vaccine, cytokine therapy, or a tyrosine kinase inhibitor.