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

A compound of Formula Ia:

• or pharmaceutically acceptable salts or prodrugs thereof, wherein:
• U is N, O, S, CR′, or NR″;
• V, and W are each, independently, N, O, S, CR2, or NR3, wherein the five-membered ring containing U, V, and W is an aromatic heterocycle;
• A is aryl, cycloalkyl, heteroaryl, or heterocycloalkyl, each 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, halosulfanyl, Cy1, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)NRcRd, NRcC(O)ORa, C(═NRi)NRcRd, NRcC(═NRi)NRcRd, P(Rf)2, P(ORe)2, P(O)ReRf, P(O)OReORf, S(O)Rb, S(O)NRcCRd, S(O)2Rb, NRcS(O)2Rb, and S(O)2NRcRd, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy1, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)NRcRd, NRcC(O)ORa, C(═NRi)NRcRd, NRcC(═NRi)NRcRd, P(Rf)2, P(ORe)2, P(O)ReRf, P(O)OReORf, S(O)Rb, S(O)NRcRd, S(O)2Rb, NRcS(O)2Rb, and S(O)2NRcRd;
• R is H, C(O)R5, C(O)OR6, or C(O)NR6aR6b;
• RA and RB are independently selected from H, F, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(═NRi)NRc1Rd1, NRcC(═NRi)NRc1Rd1, P(Rf1)2, P(ORe1)2, P(O)Re1Rf1, P(O)ORe1Rf1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1, and S(O)2NRc1Rd1;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(═NRi)NRc1Rd1, NRcC(═NRi)NRc1Rd1, P(Rf1)2, P(ORe1)2, P(O)Re1Rf1, P(O)ORe1Rf1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1, and S(O)2NRc1Rd1;
• or RA and RB together with the carbon atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl group or 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, P(Rf1)2, P(ORe1)2, P(O)Re1Rf1, P(O)ORe1Rf1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1, and S(O)2NRc1Rd1
• or RA and RB, together with the carbon atom to which they are attached, form a C═CH2 group;
• Q is ORQ, OC(O)RQ, OC(O)NR4RQ, NR4RQ, NR4C(O)RQ, NR4C(O)NR4RQ, NR4C(O)ORQ, NR4S(O)RQ, NR4S(O)2RQ, NR4C(═NRi)NR4RQ, SRQ, S(O)RQ, S(O)NR4RQ, S(O)2RQ, S(O)2NR4RQ, C(O)RQ, C(O)ORQ, C(O)NR4RQ, halo, cyano, azido, or nitro;
• or Q is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-4 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, Cy, —(C1-4 alkyl)-Cy, halosulfanyl, CN, NO2, ORa2, —(C1-4 alkyl)-ORa2, SRa2, —(C1-4 alkyl)-SRa2, C(O)Rb2, —(C1-4 alkyl)-C(O)Rb2, C(O)NRc2Rd2, —(C1-4 alkyl)-C(O)NRc2Rd2, C(O)ORa2, —(C1-4 alkyl)-C(O)ORa2, OC(O)Rb2, —(C1-4alkyl)-OC(O)Rb2, OC(O)NRc2Rd2, —(C1-4 alkyl)-OC(O)NRc2Rd2, NRc2Rd2, —(C1-4 alkyl)-NRc2Rd2, NRc2C(O)Rb2, —(C1-4alkyl)NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, —(C1-4 alkyl)-NRc2C(O)NRc2Rd2. NRc2C(O)ORa2, —(C1-4alkyl)-NRc2C(O)ORa2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, P(Rf2)2, P(ORe2)2, P(O)Re2Rf2, P(O)ORe2ORf2, S(O)Rb2, —(C1-4alkyl)-S(O)Rb2, S(O)NRc2Rd2, —(C1-4 alkyl)-S(O)NRc2Rd2, S(O)2Rb2, —(C1-4 alkyl)-S(O)2Rb2, NRc2S(O)2Rb2, —(C1-4 alkyl)-NRc2S(O)2Rb2, S(O)2NRc2Rd2, and —(C1-4 alkyl)-S(O)2 NRc2Rd2;
• RQ is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl is 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, halosulfanyl, Cy, —(C1-4 alkyl)-Cy, 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(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, P(Rf2)2, P(ORe2)2, P(O)Re2Rd2, P(O)ORe2ORf1, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2S(O)2Rb2 and S(O)2NRc2Rd2;
• or R4 and RQ together with the N atom to which they are attached form a 4-20 membered heterocycloalkyl group or 5-20 membered heteroaryl group, each 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, halosulfanyl, Cy, —(C1-4 alkyl)-Cy, CN, NO2, ORa2, —(C1-4 alkyl)-ORa2, SRa2, —(C1-4alkyl)-SRa2, C(O)Rb2, —(C1-4 alkyl)-C(O)Rb2, C(O)NRc2Rd2, —(C1-4alkyl)-C(O)NRc2Rd2, C(O)ORa2, —(C1-4 alkyl)-C(O)ORa2, OC(O)Rb2, —(C1-4 alkyl)-OC(O)Rb2, OC(O)NRc2Rd2, —(C1-4 alkyl)-OC(O)NRc2Rd2, NRc2Rd2, —(C1-4 alkyl)NRc2Rd2, NRc2C(O)Rb2, —(C1-4 alkyl)-NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, —(C1-4 alkyl)-NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, —(C1-4 alkyl)-NRc2C(O)ORa2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, P(Rf2)2, P(ORe2)2, P(O)Re2Rf2, P(O)ORe2ORf2, S(O)Rb2, —(C1-4 alkyl)-S(O)Rb2, S(O)NRc2Rd2, —(C1-4 alkyl)-S(O)NRc2Rd2, S(O)2Rb2, —(C1-4 alkyl)-S(O)2Rb2, NRc2S(O)2Rb2, —(C1-4alkyl)-NRc2S(O)2Rb2, S(O)2NRc2Rd2, and —(C1-4 alkyl)-S(O)2NRc2Rd2;
• Cy, Cy1, and Cy2 are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, halosulfanyl, 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)ORa1, C(═NRi)NRc3Rd3, NRc3C(═NRi)NRc3Rd3, P(Rf3)2, p(ORe3)2, P(O)Re3Rf3, P(O)ORe3ORa3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2 NRc3Rd3;
• R1 is H or C1-4 alkyl;
• R2 is H, halo, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, C2-4 alkynyl, CN, NO2, OH, C1-4 alkoxy, amino, C1-4 alkylamino, or C2-8 dialkylamino;
• R3 is H, C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl;
• R4 is H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C(O)—R4a, SO2—R4a, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl, wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl is 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, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halosulfanyl, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)NRc4Rd4, NRc4C(O)ORa4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, P(Rf4)2, P(ORe4)2, P(O)Re4Rf4, P(O)ORe4ORf4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, and S(O)2 NRc4Rd4;
• R4a is H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl;
• R5 and R6 are independently selected from H, C1-8 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, each optionally substituted by one or more substituents independently selected from halo, CN, NO2, OH, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, C2-8 dialkylamino, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl;
• R6a, and R6b are independently selected from H, C1-8 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, each optionally substituted by one or more substituents independently selected from halo, CN, NO2, OH, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, C2-8 dialkylamino, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl;
• Ra, Ra1, Ra3, Ra4, and Ra5 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl;
• Rb, Rb1, Rb3, Rb4, and Rb5 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-6 alkyl, C1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;
• Ra2 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl Cy2, or Cy2—(C1-6 alkyl)-, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, 3, 4, or substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, halosulfanyl, Cy2, 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(═NRi)NRc5Rd5, NRc5C(═NRi)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe1ORf5, S(O)Rb5, S(O)NRc5Rd5, Rb2, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
• Rb2 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, Cy2, or Cy2—(C1-6 alkyl)-, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, or aryl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C, 6 haloalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, halosulfanyl, Cy2, 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(═NRi)NRc5Rd5, NRc5C(═NRi)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;
• Rc and Rd are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-6 alkyl, C1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl;
• or Rc and Rd together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
• Rc1 and Rd1 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-6 alkyl, C1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl;
• or Rc1 and Rd1 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
• Rc2 and Rd2 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cy2 and Cy2—(C1-6 alkyl)-, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, is optionally substituted with 1, 2, or 3, substituents independently selected from halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, halosulfanyl, 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)ORa3, C(═NRi)NRc3Rd3, NRc3C(═NRi)NRc3Rd3, P(Rf3)2, P(ORe3)2, P(O)Re3Rf3, P(O)ORe3, S(O)Rb3S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• or Rc2 and Rd2 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3, substituents independently selected from Cy2, Cy2-(C1-6 alkyl)-, halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, halosulfanyl, 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)ORa3, C(═NRi)NRc3Rd3, NRc3C(═NRi)NRc3Rd3, P(Rf3)2, P(ORe3)2, P(O)Re3Rf3, P(O)ORe3ORf3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• Rc3 and Rd3 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-6 alkyl, C1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;
• or Rc3 and Rd3 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
• Rc4 and Rd4 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-6 alkyl, C1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;
• or Rc4 and Rd4 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
• Rc5 and Rd5 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-16 alkyl, C1-16 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;
• or Rc5 and Rd5 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
• Re, Re1, Re2, Re3, Re4, and Re5 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, (C1-6 alkoxy)-C1-6 alkyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, and heterocycloalkylalkyl;
• Rf, Rf1, Rf2, Rf3, R14, and Rf5 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• R1 is H, CN, C(O)NH2, or NO2;
• R′ is H, halo, C1-10 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, Cy-(C1-6 alkyl)-, 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)ORa3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, or S(O)2 NRc3Rd3;
• wherein said C1-10 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from CN, NO2, Cy, Cy-(C1-6 alkyl)-, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, C(═NRi)NRc3Rd3, NRc3c(═NRi)NRc3Rd3, P(Rf3)2, P(ORe3)2, P(O)Re3Rf3, P(O)ORe3ORf3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• R″ is H, C1-10 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, Cy-(C1-6 alkyl)-, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, or S(O)2NRc3Rd3;
• wherein said C1-10 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from CN, NO2, Cy, —(C1-6 alkyl)-Cy, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, C(═NRi)NRc3Rd3, NRc3C(═NRi)NRc3Rd3, P(Rf3)2, P(ORe1)2, P(O)Re3RB, P(O)ORe3ORf3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• and
• p is 2, 3, 4, 5, 6, 7, 8, 9 or 10.