| 主权项 |
1. A compound having the structure of Formula III or a pharmaceutically acceptable isomer, isotope, enantiomer, salt, ester, prodrug, hydrate or solvate thereof, wherein J has a structure of each of X1A, X1B, X2A, X2B is C, CH or N, provided that no more than one of X1A and X1B is N and no more than one of X2A and X2B is N; each of X1C, X1D, and X1E is C, CH or N; X1F is O or S; each R4 is independently H, alkyl, alkoxy, or alkyl substituted with one or more R43, halogen, perhaloalkyl, perhaloalkoxy, —CN, —OR40, or —NR41R42; W1 is —(CRaRb)i1-L1-(CRaRb)j1—R1 or R4; or W1 and R4 taken together comprise a 5- or 6-membered heterocyclic ring fused with the ring to which W1 and R4 are attached and having one, two or three heteroatoms where each such heteroatom is independently selected from O, N, and S, and where any ring atom of such heterocyclic ring may be optionally substituted with one or more-L1-R13 or R13; or W1 comprises a 5- or 6-membered heterocyclic ring fused with a phenyl ring and having one, two or three heteroatoms where each such heteroatom is independently selected from O, N, and S, and where any ring atom of such fused heterocyclic ring and phenyl ring moiety may be optionally substituted with one or more R14; L1 is —O—, —C(O)—, —OC(O)—, —C(O)—, —NR10—, —C(O)NR10—, —N(R10)—C(O)—, —N(R10)—(CH2)n—C(O)—, —N(R10)—C(O)—N(R10)—, —N(R10)—S(O2)—, —S(O2)—NR10—, or —N(S(O2)—(CH2)n—R1)2; R1 is R13, —O—(CH2)nR13, or R10; each R10, R11 and R12 is independently H or alkyl; R13 is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, or a fused bicycle of any two of such ring moieties, or R13 and R10 taken together with the N atom to which they are attached form a heterocyclic ring, where any ring atom of R13 may be optionally substituted with one or more R14 or R15; each R14 is independently H, alkyl, halo, hydroxy, cyano, alkoxy, perhaloalkyl, and perhaloalkoxy, —OR10, —(CH2)n—COOR10, —SR10, —SO—R10, —SO2R10, —(CH2)n—NR11R12, —NHCO(CH2)n—R12, —N(R11)CO(CH2)n—R12, or —NH(CH2)n—R12; R15 is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, or a fused bicycle of any two of such ring moieties, where any ring atom of R15 may be optionally substituted with one or more R14; each R5 is independently H, alkyl, alkoxy, alkyl substituted with one or more R53, halogen, perhaloalkyl, perhaloalkoxy, —CN, —OR50, or —NR51R52; W2 is —(CRaRb)i2-L2-(CRaRb)j2R2 or R5; or W2 and R5 taken together comprise a 5- or 6-membered heterocyclic ring fused with the ring to which W2 and R5 are attached and having one, two or three heteroatoms where each such heteroatom is independently selected from O, N, and S, and where any ring atom of such heterocyclic ring may be optionally substituted with one or more —(CRaRb)i2-L2-(CRaRb)j2—R2 or R2; or W2 comprises a 5- or 6-membered heterocyclic ring fused with a phenyl ring and having one, two or three heteroatoms where each such heteroatom is independently selected from O, N, and S, and where any ring atom of such heterocyclic ring or phenyl ring may be optionally substituted with one or more of R24 and wherein one ring atom of such fused ring moiety is optionally substituted with L3-R25; L2 is —O—, —C(O)—, —OC(O)—, —C(O)O—, —NR20—, —C(O)NR20—, —N(R20)—C(O)—, —N(R20)—S(O2)—, —S(O2)—NR20—, —SO2—, —O(CH2)qCO—, —CO(CH2)qO—, null, oxazolyl, oxadiazolyl, triazolyl, pyrazolyl, or pyrimidinyl; Each Ra and Rb is independently H, hydroxy, methyl, or both Ra and Rb attached to the same carbon are, taken together, oxo, or cycloalkyl; R2 is R26, —O—(CH2)n—R26, R23 or L4-R23; L4 is —O—(CH2)n—, —C═C—, —C(O)NR20—(CH2)n—, —N(R20)—C(O)—(CH2)n—, —N(R20)—S(O2)—, —S(O2)NR20—, or cyclopropylene; each R20 is independently H or alkyl; R23 is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, or a fused bicycle of any two of such ring moieties, or R23 and R20 taken together with the N atom to which they are attached form a heterocyclic ring optionally fused with aryl or heteroaryl, where any ring atom of R23 may be optionally substituted with one or more of R24 and wherein one ring atom of R23 is optionally substituted with L3-R25; each R24 is independently selected from H, halo, alkyl, hydroxy, oxo, cyano, alkoxy, perhaloalkyl, perhaloalkoxy, nitro or amino, —O—(CH2)n—R21, —(CH2)n—O—R21, —O—(CH2)n—O—R21, —(CH2)n—NR21R22, —(CH2)n—N(R21)CO(CH2)n—R21, —(CH2)n—N(R21)SO2(CH2)n—R21, —(CH2)n—SO2—N(R21)—(CH2)n—R21, —(CH2)n—CO(CH2)n—R21, —(CH2)m—COO—R21, —O—(CH2)n—COO—R21 or —(CH2)m—OCO—R21; each R21 and R22 is independently H or alkyl, —(CH2)n—COOH, or two taken together with the nitrogen atom to which they are attached can form a 3- to 7-membered heterocyclic ring; L3 is null, —O—, —(CH2)n—O—(CH2)n—, —(CH2)n—NR20—(CH2)n—; each R25 is independently cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, or a fused bicycle of any two of such ring moieties 1, where any ring atom of R25 may be optionally substituted with one or more of R24; each R26 is independently selected from H, alkyl, alkoxy, oxo, hydroxy, and hydroxy substituted alkyl; Y is —C(O)—, —CH2—, —C(O)—CH2—, or —CH2—C(O)—; Z is —(CRaRb)n—C(O)—R3, —(CRaRb)n—R3, —R34—C(O)—R3, or H; R3 is —OR30, —NR31R32, —NH(CRaRb)n—C(O)—R3, or —(CO)NHSO2R3; each R30 is independently H or alkyl; each R31 and R32 is independently H or C1-C6 alkyl optionally substituted with one or more R33, or two taken together with the N atom to which they are attached can form a 3- to 7-membered heterocyclic ring; each R33 is independently halo, hydroxyl, alkoxy, perhaloalkyl, perhaloalkoxy, carboxyl, —COO—R30, or —OR30; R34 is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where any ring atom of R34 may be optionally substituted with one or more R35; each R35 is independently H, alkyl, halo, hydroxy, cyano, alkoxy or perhaloalkyl; each R40 and R50 is independently H or alkyl; each R41 and R42 is independently H or alkyl, —(CH2)n—COO—R40, —C(O)—R40, aryl, heteroaryl, or two taken together with the N atom to which they are attached can form a 3- to 7-membered heterocyclic ring; each R51 and R52 is independently H or alkyl, —(CH2)n—COO—R50, —C(O)—R50, aryl, heteroaryl, or two taken together with the N atom to which they are attached can form a 3- to 7-membered heterocyclic ring; each R43 is independently H, halo, hydroxyl, —NR41R42, or alkoxy; each R53 is independently H, halo, hydroxyl, —NR51R52, or alkoxy; k is 1, 2, 3 or 4; each m is independently 0 or 1; each n is independently 0, 1, 2, 3 or 4; each q is independently 1 or 2; and each i1, i2, j1 and j2 is independently 0, 1, 2, 3 or 4. |
