| 主权项 |
1. A compound of Formula I or II: or a pharmaceutically acceptable salt thereof, wherein:
Ar1 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 independently selected RA1 groups;Ar2 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, or 4 independently selected RA2 groups;B is:
(i) —(CR3R4)m1—(CR1R2)—(CR3R4)m2—X;(ii) -L1-(CR3R4)—Cy1;(iii) —Cy2-(L2)a-(CR3R4)p—Cy3; or(iv) —Cy4-L3-Y;L1 is C(O)NR, C(O)O, S(O)2NR, NRC(O)NR, NRC(S)NR, S, or S(O);L2 and L3 are each independently selected from CO, C(O)O, C(O)NR, S(O)2NR, NR, NRC(O)NR, NRC(S)NR, O, S, S(O), and S(O)2;X is Cy5, CN, C(O)NR5R6, NR5C(O)R7, NR5S(O)2R7, NR5S(O)2NR5R6, NR5C(O)OR8, or S(O)2NR5R6;Y is:
(1) aryl, heteroaryl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 independently selected RB1 groups;(2) C3-7 cycloalkyl substituted by 1, 2, 3, 4, or 5 independently selected RB2 groups; or(3) C1-6 alkyl or C1-6 haloalkyl, each substituted by 1, 2, 3, 4, or 5 independently selected RX groups;Cy1, Cy2, Cy3, Cy4, and Cy5 are each independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each of which is optionally substituted by 1, 2, 3, 4, or 5 independently selected RCy groups;R is independently selected from H and C1-4 alkyl;R1 is halo, cyano, hydroxy, C1-4 alkyl, C2-4 cyanoalkyl, C2-4 alkoxyalkyl, C1-4 haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, wherein said aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted by 1, 2, 3, 4, or 5 independently selected RD groups;R2 and R4 are each independently selected from H, halo, hydroxy, C1-4 alkyl, C2-4 cyanoalkyl, C2-4 alkoxyalkyl, and C1-4 haloalkyl; R3 is independently selected from H, halo, cyano, hydroxy, C1-4 alkyl, C2-4 cyanoalkyl, C2-4 alkoxyalkyl, C1-4 haloalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, wherein said aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted by 1, 2, 3, 4, or 5 independently selected RD groups;
R5 is independently selected from H, C1-4 alkyl, C2-4 cyanoalkyl, C2-4 alkoxyalkyl, and C1-4 haloalkyl;R6, R7, and R8 are each independently selected from H, C1-4 alkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, wherein said C1-4 alkyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RD groups;or R5 and R6 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl ring optionally substituted by 1, 2, 3, 4, or 5 independently selected RD groups;each RA1 is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRCRd, NRCRd, NRc(O)Rb, NRc(O)ORa, NRc(O)NRcRd, C(═NRe)Rb, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are 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, halosulfanyl, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRCRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd; each RA2 is independently selected from halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, 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)ORa1, NRaC(O)NRc1Rd1, C(═NRe1)Rb1, C(═NRe1)NRc1Rd1, NRc1C(═NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRaS(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, (═NRe1)NRc1Rd1NRc1C(═NRe1)NRc1Rd1NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1;
each RB1, RB2, RCy, and RD is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, 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)ORa2, NRc2C(O)NRc2Rd2, C(═NRe2)Rb2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are 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, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;each RX is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, 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, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are 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, halosulfanyl, CN, NO2, OR4, Se, C(O)Rb3, C(O)NRc4Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc4Rd3, C(═NRe3)NRc4Rd3, NRc3C(═NRe3)NRc4Rd3, NRc4Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc4Rd3, S(O)Rb3, S(O)2Rb3, NRc4S(O)2NRc4Rd3, S(O)Rb3, S(O)NRc4Rd3, S(O)2Rb3, and S(O)2NRc4Rd3;each Ra, Rb, Rc, and Rd is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)NRc4Rd4, NRc4C(O)ORa4, C(═NRf4)NRc4Rd4 NRc4C(═NRf4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;or any Rc and Rd together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, CN, 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)ORa4C(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)NRc4Rd4, S(O)2Rb4NRc4, S(O)2Rb4, NRc4S(O)2NRc4, Rd4, S(O)2NRc4Rd4, and S(O)2NRc4Rd4, wherein said C1-6 alkyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, 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(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)Rb4S(O)NRc4Rd4, S(O)2Rb4 NRc4S(O)2Rb4, NRc4S(O)2Rb4, S(O)2NRc4Rd4, and S(O)2NRc4Rd4;each Re and Rf is independently selected from H, C1-4 alkyl, CN, ORa4, SRb4, S(O)2Rb4, C(O)Rb4, S(O)2NRc4Rd4, and C(O)NRc4Rd4;each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, CN, 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)OR4, C(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;or any Rc1 and Rd1 together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, CN, 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(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;each Re1 and Rf1 is independently selected from H, C1-4 alkyl, CN, ORa4, SRb4, S(O)2Rb4, C(O)Rb4, S(O)2NRc4Rd4, and C(O)NRc4Rd4; each Ra2, Rb2, Rc2, and Rd2 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, CN, 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(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;
or any Rc2 and Rd2 together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, CN, 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(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4, wherein said C1-6 alkyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, 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(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, K (O)2NRc4Rd4, and S(O)2NRc4Rd4;each Re2 and Rf2 is independently selected from H, C1-4 alkyl, CN, ORa4, SRb4, S(O)2Rb4, C(O)Rb4, S(O)2NRc4Rd4, and C(O)NRc4Rd4; each Ra3Rb3, Rc3, and Rd3 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, 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 C1-4 alkyl, C1-4 haloalkyl, halo, CN, 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(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4; or any Rc3 and Rd3 together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, halo, CN, 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)OR4, C(═NRf4)NRc4Rd4, NRc4C(═NRf4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;
each Re3 and Rf3 is independently selected from H, C1-4 alkyl, CN, ORa4, SRb4, S(O)2Rb4, C(O)Rb4, S(O)2NRc4Rd4, and C(O)NRc4Rd4;each Ra4, Rb4, Rc4, and Rd4 is independently selected from H, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, and C2-4 alkynyl, wherein said C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, or C2-4 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino, di(C1-4 alkyl)amino, C1-4 haloalkyl, and C1-4 haloalkoxy;or any Rc4 and Rd4 together with the N atom to which they are attached form a 3-, 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, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino, di(C1-4 alkyl)amino, C1-4 haloalkyl, and C1-4 haloalkoxy;each Re4 and Rf4 is independently selected from H, C1-4 alkyl, and CN;a is 0 or 1;m1 is 0, 1, 2, 3, or 4;m2 is 0, 1, 2, 3, or 4;n is 1, 2, 3, 4, 5, or 6; andp is 1, 2, 3, 4, 5, or 6. |
