| 主权项 |
1. A compound of formula (I), or a pharmaceutically acceptable salt thereof: Wherein J is a group of formula IIa or IIb: wherein R1a is C1-C3 alkyl, C2-C3 alkylene-OH, or C1-C3 haloalkyl; Y1a is N or CRxa, wherein Rxa is H, halo, C1-C3 alkyl, —O—C1-C3 alkyl, C1-C3 haloalkyl, —O—C1-C3 haloalkyl, aryl, aryl-C1-C3alkylene-OH, aryl-C1-C3alkylene-heterocycloalkyl, C(O)NR10R12, wherein heterocycloalkyl of aryl-C1-C3alkylene-heterocycloalkyl may be substituted with one to three C1-C3alkyl,
R1b is H, C1-C3 alkyl, C2-C3 alkylene-OH, or C1-C3 haloalkyl;Y1b is N or CRxb, wherein Rxb is heteroaryl, H, halo, C1-C3 alkyl, —O—C1-C3 alkyl, C1-C3 haloalkyl, —O—C1-C3 haloalkyl, aryl, aryl-C1-C3alkylene-OH, aryl-C1-C3alkylene-heterocycloalkyl, C(O)NR10R12, wherein heterocycloalkyl of aryl-C1-C3alkylene-heterocycloalkyl may be substituted with one to three C1-C3alkyl; wherein said heteroaryl may be substituted with one to three groups selected from the group consisting of: C1-C6 alkyl, C1-C3alkylene-aryl, C1-C3alkylene-heteroaryl, C1-C3alkylene-heterocycloalkyl, COOH, and COO—C1-C4alkyl,X2a is selected from the group consisting of: H, —NR10R12, halo, OH, —O—C1-C4 alkyl, aryl, heteroaryl, —NR10C(O)—C1-C4 alkyl, NR10C(O)O—C1-C6 alkyl, and NR10S(O)2—C1-C6 alkyl;X2b is C1-C3 alkyl, C2-C3 alkylene-OH, or C1-C3 haloalkyl;X1a and X1b are each selected from the group consisting of: hydrogen, halo, C1-C6 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, —C2-C4 alkenylene-O—C1-C6 alkyl, C2-C4 alkynyl, —C2-C4 alkynylene-N(C1-C6 alkyl)2, —O—C1-C6 alkyl, —O—CD2CH3, —O—CD2CD3, —O—C3-C7 cycloalkyl, —O-heterocycloalkyl, —O-aryl, —O—C1-C3 alkylene-C3-C7 cycloalkyl, —O—C1-C3 alkylene-heterocycloalkyl, —O—C1-C3 alkylene-aryl, wherein the aryl groups of the —O-aryl and —O—C1-C3 alkylene-aryl, the C3-C7 cycloalkyl groups of the —O—C3-C7 cycloalkyl and —O—C1-C3 alkylene-C3-C7 cycloalkyl, and the heterocycloalkyl groups of the —O-heterocycloalkyl and —O—C1-C3 alkylene-heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of oxo, halo, —CN, C1-C6 alkyl, C1-C6 haloalkyl, NH2, N(H)(alkyl), N(alkyl)2, —C(O)OC1-C6 alkyl, and —C1-C3 alkylene-heterocycloalkyl, —O—C1-C4 haloalkyl, OH, —O—C1-C6 alkylene-OH, —O—C1-C6 alkylene-N(R10)2, —O—C1-C3 alkylene-C(O)O—C1-C4 alkyl, —NR10—C1-C6 alkyl, —NR10—C1-C6 haloalkyl, —NR10—C(O)OC1-C6 alkyl, —NR10—C(O)OC1-C6haloalkyl, —NR10—C(O)NR10R12, —NR10—SO2R12, —NR10—C3-C7 cycloalkyl, —NR10—C1-C3 alkylene-C3-C7 cycloalkyl, C1-C4 alkylene-OH, —C1-C3 alkylene-C(O)OC1-C4 alkyl, C1-C3 alkylene-NR10C(O)—C1-C4 alkyl, —C1-C3 alkylene-C(O)NR10R12, —C2-C4 alkenylene-C(O)—O—C1-C4 alkyl, —C(O)—C1-C4 alkyl, C(O)O—C1-C4 alkyl, C(O)NR10R12, —NR10C(O)—C1-C4 alkyl, —NR10—C1-C3 alkylene-C(O)—C1-C4 alkyl, —NR10—C1-C3 alkylene-C(O)O—C1-C4 alkyl, —SO2NR10R12, and any of groups i-v:
i) C3-C14 cycloalkyl, which is optionally substituted with 1 to 3 of R2, where R2 is selected from the group consisting of: halo, oxo, CN, —O—C1-C4 alkyl, —O—C1-C4 haloalkyl, —NR10R12, C(O)NR10R12, C1-C4 alkyl, C1-C4 haloalkyl, C(O)—C1-C4 alkyl, —C(O)O—C1-C4 alkyl, SO2NR10R12, SO2—C1-C4 alkyl, and aryl, wherein said aryl is optionally substituted with 1 to 3 substituents independently selected from group consisting of: halo, C1-C3 alkyl, C(O)—C1-C3alkyl, C(O)OH, C(O)NR10R12, and heteroaryl;ii) heterocycloalkenyl, which is optionally substituted with 1 to 3 of R2, where R2 is selected from the group consisting of: halo, oxo, CN, —O—C1-C4 alkyl, —O—C1-C4 haloalkyl, —NR10R12, C(O)NR10R12, C1-C4 alkyl, C1-C4 haloalkyl, C(O)—C1-C4 alkyl, —C(O)O—C1-C4 alkyl, SO2NR10R12, SO2—C1-C4 alkyl, and aryl, wherein said aryl is optionally substituted with 1 to 3 substituents independently selected from group consisting of: halo, C1-C3 alkyl, C(O)—C1-C3alkyl, C(O)OH, C(O)NR10R12, and heteroaryl;iii) heterocycloalkyl, which is optionally substituted with 1 to 3 of R3, where R3 is selected from the group consisting of: halo, oxo, CN, —O—C1-C4 alkyl, —O—C1-C4 haloalkyl, —NR10R12, C(O)NR10R12, C1-C4 alkyl, C1-C4 haloalkyl, C(O)—C1-C4 alkyl, —C(O)O—C1-C4 alkyl, SO2NR10R12, SO2—C1-C4 alkyl, and aryl, wherein said aryl is optionally substituted with 1 to 3 substituents independently selected from group consisting of: halo, C1-C3 alkyl, C(O)—C1-C3alkyl, C(O)OH, C(O)NR10R12, and heteroaryl;iv) heteroaryl, which is optionally substituted with 1 to 3 of R4, where R4 is selected from the group consisting of: halo, oxo, CN, —O—C1-C4 alkyl, —O—C1-C4 haloalkyl, —NR10R12, —C(O)H, C(O)NR10R12, C1-C6 alkyl, C1-C4 haloalkyl, C1-C6 alkylene-heterocycloalkyl, C1-C6alkylene-aryl, C1-C6 alkylene-heteroaryl, C(O)—C1-C4 alkyl, —C(O)O—C1-C4 alkyl, SO2NR10R12, SO2—C1-C4 alkyl, —NR14C(O)C1-C4-alkyl, heterocycloalkyl, and aryl, wherein said aryl is optionally substituted with 1 to 3 substituents independently selected from group consisting of: halo, C1-C3 alkyl, C(O)—C1-C3alkyl, C(O)OH, C(O)NR10R12, and heteroaryl,wherein said heterocycloalkyl or heterocycloalkyl group of C1-C6 alkylene-heterocycloalkyl is optionally substituted with 1 to 3 independently selected C1-C3 alkyl groups, and wherein said heteroaryl group of C1-C6 alkylene-heteroaryl and said aryl groups of C1-C6 alkylene-aryl is optionally substituted with substituents 1 to 3 groups independently selected from C1-C3 alkyl and NR14R16;v) aryl, which is optionally substituted with 1 to 3 of R6, where R6 is selected from the group consisting of: halo, CN, —NR14R16, —N(R14)C(O)—C1-C4 alkyl, —NR14SO2—C1-C4 alkyl, C(O)H, C(O)C1-C6 alkyl, C(O)heterocycloalkyl, C(O)NR14R16, —C1-C4 alkylene-NR14R16, SO2NR14R16, C(O)OC1-C4 alkyl, —SO2— heterocycloalkyl, —SO2—C1-C6 alkyl, —C1-C6 alkyl, —OH, —O—C1-C6 alkyl, —C1-C6 haloalkyl, —O—C1-C6 haloalkyl, —C1-C6 alkylene-OH, —C(H)(OH)(C3-C7 cycloalkyl), —C(H)(OH)(phenyl), C2-C4 alkenylene-OH, —C1-C6 alkylene-O—C1-C6 alkyl, —C1-C6 alkylene-OC(O)—C1-C6 alkyl, —C1-C6 alkylene-C(O)O—C1-C6 alkyl, —C1-C6 alkylene-N(H)SO2—C1-C6 alkyl, —C1-C6 alkylene-N(H)C(O)—C1-C6 alkyl, —C1-C6 alkylene-CN, —C1-C6 alkylene-heterocycloalkyl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, and heterocycloalkyl,wherein said heterocycloalkyl and said heterocycloalkyl of said C(O)heterocycloalkyl and said C1-C6 alkylene-heterocycloalkyl is optionally substituted with 1 to 3 groups independently selected from the group consisting of C1-C6 alkyl, and C1-C4 alkylene-aryl,wherein said heteroaryl and the heteroaryl of said C1-C6 alkylene-heteroaryl, and the aryl of said C1-C6 alkylene-aryl is optionally substituted with 1 to 3 groups independently selected from the group consisting of C1-C4 alkyl, C1-C4 haloalkyl, halo, —C1-C3 alkylene-CN, —C1-C3 alkylene-OH, —C1-C3 alkylene-C(O)O—C1-C3 alkyl, —C1-C3 alkylene-O—C1-C3 alkyl, —C1-C3 alkylene-OC(O)—C1-C3 alkyl, —C1-C3 alkylene-NR14-aryl, C1-C3 alkylene-NR14—C(O)—C1-C4alkyl, —C1-C3 alkylene-NR14SO2—C1-C4 alkyl, —C(O)—C1-C3 alkyl, and —C(O)-heterocycloalkyl, wherein said heterocycloalkyl of C(O)-heterocycloalkyl is optionally substituted with 1 to 3 groups independently selected from the group consisting of: C1-C6 alkyl, —C(O)—NHCH2-aryl, —CH—(OH)—C1-C6 alkyl, —CH(OH)—C2-C6 alkenyl, —CH(OH)—C3-C7 cycloalkyl, —CH(OH)-phenyl, —C(O)NR14R16—C3-C14cycloalkyl, —C(O)NR14—C1-C3 alkylene-NR14R16, —C(O)NR14—C1-C3 alkylene-CN, —C(O)NR14—C1-C3 alkylene-NR14R16, —C(O)NR14R16, —C(O)NH—C3-C14 cycloalkyl, —C(O)NH—C1-C3 alkylene-O—C1-C3 alkyl, C(O)NH—C1-C3 alkylene-OH, —NR14—C3-C14 cycloalkyl, —NR14—C1-C3 alkylene-heterocycloalkyl, —NR14C(O)—C1-C4 alkyl, heterocycloalkyl, and heteroaryl, wherein said heterocycloalkyl or heteroaryl is optionally substituted with 1-3 substituents independently selected from the group consisting of: halo, C1-C4 alkyl, C1-C4 haloalkyl, and aryl;where R14 and R16 are independently selected from the group consisting of: C1-C4 alkyl, C3-C7-cycloalkyl, —C1-C3-alkylene-NR10R12, —C1-C3-alkylene-OR12, —C1-C3-alkylene-CN, aryl, C3-C7 cycloalkyl, C1-C3-alkylene-aryl, and H,where R10 and R12 are at each occurrence independently selected from the group consisting of H, C1-C6 alkyl, C1-C3-alkylene-aryl, C1-C3-alkylene-heteroaryl, C1-C3-alkylene-C3-C7-cycloalkyl, —C1-C3-alkylene-heterocycloalkyl, and C3-C7 cycloalkyl;where X3 is L-G, where L is absent or is selected from the group consisting of:
—O—, —O—C1-C3 alkylene-, —NR30—, —NR30—C1-C3 alkylene-, —C(O)—, —C1-C3 alkylene- wherein said C1-C3 alkylene is optionally substituted with one to two substituents independently selected from the group consisting of: OH, —NR20R22, —NH-heterocycloalkyl, and —O—C1-C3 alkyl, and wherein R30 is H, C1-C4 alkyl, or C1-C4 haloalkyl; andG is selected from the group consisting of:aryl, heteroaryl, C2-C6 alkyl, C3-C7 cycloalkyl, and heterocycloalkyl, wherein G is optionally substituted with 1 to 3 groups independently selected from the group consisting of halo, CN, OH, —C1-C4 alkyl, —C2-C4 alkynyl substituted with a C2-C4 alkenyl or OH, —C1-C4 haloalkyl, —SO2—R32, —O—R32, —C(O)—R32, —C(O)O—R32, —C(O)NR20R22, —NR20R22, —NR20C(O)OR32, —NR20C(O)R32, —NR20SO2R34, —NR20C(O)NR36R38, —O-heterocycloalkyl, aryl, and heterocycloalkyl, and the aryl and the heterocycloalkyl is optionally substituted with one to three groups independently selected from the group consisting of halo, CN, OH, —C1-C4 alkyl, C(O)OC1-C6 alkyl, O—C1-C4 haloalkyl, and —C1-C4 haloalkyl,
wherein R32 is selected from —C1-C4 alkyl and —C1-C4 haloalkyl,wherein R34 is selected from —C1-C4 alkyl and —C1-C4 haloalkyl,wherein R36 and R38 are independently selected from the group consisting of hydrogen, —C1-C4 alkyl, and —C1-C3 haloalkyl;where A2 is CR18, and A1, A3, and A4 are CR19, where R19 is H;wherein R18 is selected from the group consisting of: H, NO2, CN, C1-C3 alkyene-SO2—C1-C6 alkyl, C1-C3 alkyene-SO2—C1-C6 haloalkyl, C1-C3 alkyene-SO2—NR20R22, —NR20R22, —NHSO2—NR20R22, —NR40SO2—C1-C4 alkyl, —NR40SO2—C1-C4 haloalkyl, —NR40SO2—CH2—C(O)OH, —NR40SO2—CH2—C(O)OC1-C4 alkyl, —NR40SO2—C3-C7 cycloalkyl, —NR40SO2-aryl, —NR40SO2-heteroaryl, —NR40SO2—C1-C3 alkylene-C3-C14 cycloalkyl, —NR40SO2—C1-C3 alkylene-heterocycloalkyl, —NR40SO2—C1-C3 alkylene-heteroaryl, —NR40SO2—C1-C3 alkylene-aryl, —SO2—NR40R42, —SO2—NR40—C1-C4 haloalkyl, —SO2—NR40—C3-C14 cycloalkyl, —SO2—NR40—C(O)NR20R22, —SO2—NR40-heterocycloalkyl, —SO2—NR40-heteroaryl, —SO2—NR40-aryl, —SO2—C1-C6 alkyl, —SO2—C1-C6 haloalkyl, —SO2—C3-C14 cycloalkyl, —SO2— heterocycloalkyl, —SO2-heteroaryl, —SO2-aryl, —NR40SO2—NR20R22, —NR40C(O)—C1-C6 alkyl, —NR40C(O)NH—C1-C4 alkyl, —NR40C(O)-heteroaryl, —NR40C(O)-heterocycloalkyl, —NR40C(O)-aryl, —NR40C(O)—C3-C14 cycloalkyl, —NR40C(O)O—C1-C4 alkyl, —NR40C(O)O-heteroaryl, —NR40C(O)—CH2NH—C(O)O—C1-C4 alkyl, —NR40C(O)—CH2NR20R22, —C(O)CH2—NR20R22, —C(O)NR20R22, C(O)OH, —C1-C3 alkylene-NR40—C(O)—C1-C4 alkyl, —C1-C3 alkylene-NR40—C(O)—C1-C3 haloalkyl, —NR40-heteroaryl, C3-C14 cycloalkyl, heterocycloalkyl, heterocycloalkyl-aryl, heteroaryl, aryl, —C1-C3 alkylene-cycloalkyl, —C1-C3 alkylene-heterocycloalkyl, —C1-C3 alkylene-heteroaryl, and —C1-C3 alkylene-aryl,wherein any of the cycloalkyl, C3-C7 cycloalkyl, C3-C14 cycloalkyl, heterocycloalkyl, heteroaryl, or aryl groups of R18 is optionally substituted with 1 to 3 of C1-C4 alkyl, C1-C4 haloalkyl, halo, oxo, —OH, —O—C1-C6 alkyl, —O—C1-C6 haloalkyl, —OG1, —S(O)2—C1-C6 alkyl, —N(R40)2, —N(R40)C(O)C1-C6 alkyl, G1, —C1-C6 alkylene-G1, or —C1-C6 alkylene-OG1, wherein G1 is cycloalkyl, heterocycloalkyl, heteroaryl, or aryl, and each G1 is optionally substituted with 1 to 3 of oxo, C1-C4 alkyl, C1-C4 haloalkyl, or halo,wherein R40 and R42 are independently selected from the group consisting of: H and C1-C4 alkyl, andwherein R20 and R22 are at each occurrence independently selected from the group consisting of: H and C1-C6 alkyl. |
