Compounds as modulators of tlr2 signaling

A compound of Formula (A)

• or a tautomer, or a pharmaceutically acceptable salt of any of the foregoing,
• wherein
• indicates that the ring is saturated, partially unsaturated, or fully unsaturated;
• indicates that the
• is attached in either the E or Z configuration;
• G1 and G2 are each independently CRx, or N;
• Rx is hydrogen or halogen;
• one of R1 and R2 is —OH and the other is selected from the group consisting of —C(O)Ra, —CH═NRj, —S(O)Rb, —S(O)2Rc, —NHC(O)Rd, —NHS(O)2Re, —C1-C6alkyl-Rf, —C2-C6alkenyl-Rg, unsubstituted or substituted C3-C8 cycloalkyl, unsubstituted or substituted C3-C8 cycloalkenyl, and unsubstituted or substituted heterocycloalkyl;
• Ra, Rb, Rc, and Re are each independently H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heteroaryl, benzoyl, or styryl;
• Rd is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heteroaryl, or benzoyl;
• Rf and Rg are each independently —OH, unsubstituted heteroaryl, —NRmRn benzoyl, or styryl;
• Rm and Rn are each independently H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, or unsubstituted or substituted cycloalkyl;
• Rj is unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, —ORk, —NHRk, —NHC(O)Rk, —NHS(O)2Rk, or —NHC(NH)NH2;
• Rk is C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8 cycloalkyl, or aryl;
• R3 is H, C1-C6alkyl, C1-C6alkoxy, or halogen, wherein the C1-C6alkyl and C1-C6alkoxy of R3 are each independently unsubstituted or substituted with one or more halogen;
• wherein:
• when R1 or R2 is —C1-C6alkyl-OH or —C1-C6alkyl-NRmRn, wherein Rj and IV are each C1-C6alkyl, R3 is selected from the group consisting of C1-C6alkyl, C2-C6alkoxy, and halogen;
• when R1 or R2 is unsubstituted or substituted C3-C8 cycloalkyl, —NHC(O)CH3, or —S(O)2-Rc, wherein Rc is an unsubstituted or substituted heterocyclyl, R3 is selected from the group consisting of C1-C6alkyl, C1-C6alkoxy, and halogen;
• when R1 or R2 is —CHO, R3 is selected from the group consisting of hydrogen, C2-C6alkoxy, and halogen;
• when R1 or R2 is —C(O)CH3, R3 is selected from the group consisting of C2-C6alkoxy and halogen;
• when R1 or R2 is —C(O)CH(Br)CH3 or —C(O)CH(Br)CH2CH3, G7 is C or CH;
• when R3 is hydrogen, no more than one of R6a, R6b, R6c, and R6d is —CF3, no more than one of R6a, R6b, R6c, and R6d is —CH3, and no more than one of R6a, R6b, R6c, and R6d is —OH,
• Y is absent and R4 and R5 come together to form —S—;
• G3 is CH(X1-R6a), C(X1-R6a), N, N(X1-R6a), S, or O;
• G4 is CH(X2-R6b), C(X2-R6b), N, N(X2-R6b), S, or O;
• G5 is CH(X3-R6c), C(X3-R6c), N, N(X3-R6c), S, or O;
• G6 is CH(X4-R6d), C(X4-R6d), N, N(X4-R6d), S, O, or absent;
• G7 is N, C, or CH;
• X1, X2, X3, and X4 are each independently absent,
• m is 1-6;
• R6a, R6bR6c, and R6d are each independently hydrogen, C1-C6alkyl, C1-C6alkoxy, halo, —OH, —NRpRq, aryl, heterocyclyl, heteroaryl, —C1-C6alkyl-heterocyclyl, —OC(O)-heterocyclyl, —C(O)Rh, —S(O)2NRw1Rw2, —S(O)2Ry, or —NRz1S(O)2Rz2, wherein the C1-C6alkyl and C1-C6alkoxy of R6a, R6b, R6c and R6d are each independently unsubstituted or substituted with one or more groups selected from the group consisting of cycloalkyl and halogen;
• the aryl and heteroaryl of R6a, R6b, R6c and R6d are each independently unsubstituted or substituted with one or more groups selected from the group consisting of C1-C6alkyl, C1-C6alkoxy, —OH, and C1-C6alkyl-OH;
• and the heterocyclyl, —C1-C6alkyl-heterocyclyl, and —OC(O)-heterocyclyl of R6a, R6b, R6c and R6d are each independently unsubstituted or substituted with one or more groups selected from the group consisting of C1-C6alkyl, C1-C6alkoxy, —OH, C1-C6alkyl-OH, ═O, and ═S;
• Rh is selected from the group consisting of H, C1-C6alkyl, C1-C6alkoxy, and C3-C6cycloalkyl, and —NRrRs,
• Rp is H or C1-C6alkyl;
• Rq is C2-C3alkyl, —C(O)Rt, —C(O)ORu, —C(O)NRv;
• Rr, Rs, Rw1, and Rz1 each independently selected from H and C1-C6alkyl;
• and
• Rt, Ru, Rv, Rw2, Ry, and Rz2 are each independently selected from H, C1-C6alkyl, unsubstituted or substituted C3-C8cycloalkyl, and unsubstituted or substituted heterocyclyl;
• or
• G5 is CH(X3-R6c) or C(X3-R6c), G6 is CH(X4—R6d) or C(X4-R6d), and R6c and R6d are taken together with the carbons to which they are attached to form a 6-membered aryl, a 6-membered heterocyclyl, or a 6-membered heteroaryl ring;
• wherein the 6-membered aryl, 6-membered heterocyclyl, and 6-membered heteroaryl rings are each independently unsubstituted or substituted;
• and
• wherein no more than one of R6a, R6b, R6c, and R6d is C1-C6alkoxy or —OH.