N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase

A compound of Formula I:

• or pharmaceutically acceptable salt thereof, wherein:
• Q is C1-6 alkyl substituted by phenyl, wherein said phenyl is substituted by 1, 2, or 3 substituents independently selected from halo and C1-4 alkyl;
• or
• Q is aryl optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy4, —(C1-4 alkyl)-Cy4, CN, NO2, ORa4—(C1-4 alkyl)-ORa4, SRa4, —(C1-4 alkyl)-SRa4, C(O)Rb4, —(C1-4 alkyl)-C(O)Rb4, C(O)NRc4Rd4, —(C1-4 alkyl)-C(O)NRc4Rd4, C(O)ORa4, —(C1-4 alkyl)-C(O)ORa4, OC(O)Rb4, —(C1-4 alkyl)-OC(O)Rb4, OC(O)NRc4Rd4, —(C1-4 alkyl)-OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, —(C1-4alkyl)-NRc4CORb4, NRc4C(O)NRc4Rd4, —(C1-4alkyl)-NRc4,C(O)NRc4Rd4, NRc4C(O)ORa4, —(C1-4 alkyl)-NRc4C(O)ORa4, C(═NRi4)NRc4Rd4, NRc4C(═NRi4)NRc4Rd4, P(Rf4)2, P(O)Re4Rf4, P(O)ORe4ORf4, S(O)Rb4, —(C1-4alkyl)-S(O)Rb4, S(O)NRc4Rd4, —(C1-4 alkyl)-S(O)NRc4Rd4, S(O)2Rb4, —(C1-4 alkyl)-S(O)2Rb4, NRc4S(O)2Rb4, —(C1-4 alkyl)-NR(O)c4S(O)2Rb4, S(O)2NRc4Rd4, and —(C1-4 alkyl)-S(O)2NRc4Rd4;
• R2 is halo, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, pentahalosulfanyl, Cy3, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)NRc3Rd3, NRc3C(O)ORa3, C(═NRi3)NRc3Rd3, NRc3C(═NRi3)NRc3Rd3, P(Rf3)2, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, NRc3S(O)2Rb3, or S(O)2NRc3Rd3;
• wherein said C1-10 alkyl, C2-10 alkenyl, or C2-10 alkynyl, is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-10 cyanoalkyl, pentahalosulfanyl, Cy3, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)NRc3Rd3, NRc3C(O)ORa3, C(═NRi3)NRc3Rd3, NRc3C(═NRi3)NRc3Rd3, P(Rf3)2, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, NRc3S(O)2Rb3, and S(O)2NRc3Rd3;
• R4 is selected from H, halo, C1-4 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
• R5 is H;
• or R2 and R4 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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy2, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, C(═NRi2)NRc2Rd2, NRc2C(═NRi2)NRc2Rd2, P(Rf2)2, P(ORe2)2, P(O)Re2Rf2, P(O)ORe2ORf2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy2, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, C(═NRi2)NRc2Rd2NRc2C(═NRi2)NRc2Rd2, P(Rf2)2, P(ORe2)2, P(O)Re2Rf2, P(O)ORe2ORf2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2S(O)2Rb2, and S(O)2NRc2Rd2;
• Ra3 and Ra4 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cy5, and Cy5—(C1-6 alkyl)-, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy5, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi5)NRc5Rd5, NRc5C(═NRi5)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
• Rb3 and Rb4 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cy5, and Cy5—(C1-6 alkyl)-, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy5, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi5)NRc5Rd5, NRc5C(═NRi5)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
• Rc3 and Rc4 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)Rb5, C(O)NRc5Rd5, C(═NRi5)NRc5Rd5, Cy5, and Cy5—(C1-6 alkyl)-, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy5, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi5)NRc5Rd5, NRc5C(═NRi5)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
• Rd3 and Rd4 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)Rb5, C(O)NRc5Rd5, C(═NRi5)NRc5Rd5, Cy5, and Cy5-(C1-6 alkyl)-, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy5, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi5)NRc5Rd5, NRc5(═NRi5)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
• or Rc3 and Rd3 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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy5, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi5)NRc5Rd5, NRc5C(═NRi5)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
• or Rc4 and Rd4 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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy5, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi5)NRc5Rd5, NRc5C(═NRi5)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
• Cy2, Cy3, Cy4, and Cy5 are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents selected from halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, pentahalosulfanyl, CN, NO2, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc5Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, C(═NRi6)NRc6Rd6, NRc6C(═NRi6)NRc6Rd6, P(Rf6)2, P(ORe6)2, P(O)Re6Rf6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, and S(O)2NRc6Rd6;
• Ra2, Ra5, and Ra6 are independently selected from H, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 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, C1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
• Rb2, Rb5, and Rb6 are independently selected from H, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents indpendently selected from OH, amino, halo, C1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
• Rc2, Rc5, and Rc6 are independently selected from H, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 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, C1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
• Rd2, Rd5, and Rd6 are independently selected from H, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 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, C1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
• Re2, Re5, and Re6 are independently selected from H, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 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, C1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
• Rf2, Rf3, Rf4, Rf5, and Rf6 are independently selected from H, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 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, C1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
• and
• Ri2, Ri3, Ri4, Ri5,and Ri6 are independently selected from H, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 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, C1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl.