主权项 |
1. A compound of Formula IIC: or a pharmaceutically acceptable salt form thereof, wherein: R is selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; Q1, Q2, and Q3 are independently selected from CRQ and N; RQ is independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; Cyb is a substituted aryl or substituted heteroaryl ring according to Formula IF: wherein: W1 and W2 are independently selected from CRW and N; A1 and A2 are independently selected from CRW and N; or the group A1=A2 is S, O, or NH; and each RW is independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; L is a divalent moiety selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, (C1-6 alkylene)p-(C3-10 cycloalkylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C3-10 heterocycloalkylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C6-10 arylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C3-10 heteroarylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-O-(C1-6 alkylene)q, (C1-6 alkylene)p-S-(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3—(C1-6 alkylene)q, (C 1-6 alkylene)p-C(O)—(C1-6 alkylene)q, (C 1-6 alkylene)p-OC(O)—(C1-6 alkylene)q, (C 1-6 alkylene)p-C(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)NRc3—(C1-6 alkylene)q, (C 1-6 alkylene)p-S(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-S(O)2—(C1-6 alkylene)q, (C1-6 alkylene)p-S(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-S(O)2NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3C(O)NRd3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3S(O)NRd3—(C1-6 alkylene)q, and (C1-6 alkylene)p-NRc3S(O)2NRd3—(C1-6 alkylene)q, wherein each of the C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, cycloalkylene, arylene, heterocycloalkylene, and heteroarylene is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, CN, NO2, SCN, OH, C1-4 haloalkyl, halosulfanyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, and C2-8 dialkylamino;wherein L is oriented in either direction with respect to its attachment to Cyb and the ring containing Q1, Q2, and Q3;
Z1 is CR6; Z2 is CR7; R1 is selected from H, C1-6 alkyl, C(O)C1-6 alkyl, and C(O)aryl; R2, R3, R4, and R5 are independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy1, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from CN, NO2, Cy1, Cy1-(C1-6 alkyl)-, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4; R6 is H; R7 is H; 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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, CN, NO2, N3, 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, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-6 haloalkyl, halosulfanyl, CN, NO2, N3, 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; Ra1, Ra2, and Ra4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C(O)—C1-7 hydrocarbyl, wherein said C1-6 alkyl, C2-6 alkenyl, C1-7 hydrocarbyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Rb1, Rb2, and Rb4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Rc1, Rc2, and Rc4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Rd1, Rd2, and Rd4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; or, one or more of Rc1 and Rd1, Rc2 and Rd2, and Rc4 and Rd4 together with the N atom to which they are attached, optionally form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Rc3 and Rd3 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Ra5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or 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 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 halo alkoxy; Rb5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or 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 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; 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 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; or Rc5 and Rd5 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; Re5 is 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, or heterocycloalkylalkyl; Rf5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl; Ri is H, CN, NO2, C(O)NH2, or C1-6 alkyl; p is 0 or 1; and q is 0 or 1. |