Conjugated TLR7 and/or TLR8 and TLR2 polycationic agonists

A conjugated compound of Formula I:

• Q-Z—R4 Formula I
• wherein Q is an imidazoquinoline, a purine or a 3-deazapurine derivative agonist of TLR7 and/or TLR8 t and Z—R4 is a TLR2 agonist,
• said conjugated compound being chosen among compounds of Formula II:
• a tautomer thereof or a pharmaceutically acceptable salt, solvate or polymorph of said compound or tautomer, wherein:
• R1 is —H, —OH, —SH, —NH2, —CF3, halogen, or a group chosen from C1-C6alkyl, C1-C6alkylamino, C1-C6alkoxy, C3-C6cycloalkyl-C1-C6alkyl, C3-C6cycloalkyl-C1-C6alkylamino, C3-C6cycloalkyl, C1-C6alkoxyC1-C6alkylamino, or C1-C6alkoxyC1-C6alkoxy, (C1-C6alkyl)-E-(C1-C6alkylene)- wherein E is —O—, —S—, —N(R12)—, —C(O)— or —S(O)2— and R12 is —H, carboxyl, —NH2, C1-C6alkyl, C1-C6alkoxy, C1-C6alkanoyl, C6-C20aryl, C6-C20 heteroaryl, or C1-C6alkoxycarbonyl, said group being optionally terminally substituted with a hydroxyl, amino, thiol, hydrazino, hydrazido, azido, acetylenyl, carboxyl, or maleimido group;
• A is a nitrogen atom, R3 is absent and R2 is H, OH, SH, NH2, CF3, halogen, C1-C10alkyl, C1-C10alkylamino, C1-C10dialkylamino, C1-C10alkoxy, C1-C10alkoxy-C1-C10 alkylamino, C1-C10alkoxy-C1-C10alkoxy, C1-C10alkoxy-C5-C7heterocycle, C1-C10alkyamino-C5-C7heterocycle, —NH—SO2—C1-C6alkyl, —C(O)—C1-C6alkyl, —O—C(O)—C1-C6alkyl, —C(O)—C1-C10alkylamino, —C(O)—C1-C10dialkylamino, C5-C10aryl, C5-C9heterocyclyl, C3-C9 carbocyclyl, C1-C10alkylamino-C2-C7heterocycle, (C1-C6alkoxy)-E-(C1-C6alkylene) and preferably R1 is —H, —OH, —SH, —NH2, C1-C6alkyl, such as methyl, ethyl, propyl or butyl, C1-C6alkylamino such as methylamino, ethylamino, propylamino or butylamino, C1-C6alkoxy such as methoxy, ethoxy, propoxy or butoxy, (C1-C6alkyl)-E-(C1-C6alkylene), wherein E is —O— or —NH—, such as —CH2—NH—C2H5, —CH2—O—C2H5, —(CH2)2—NH—CH3, or —(CH2)2—O—CH3, more preferably R1 is —OH, or
• A is a carbon atom and R2 and R3 form together a fused phenyl optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CH3, —CH2CH3, CH2CH(CH3)2, —CH2OH, —CH2CH2OH, —C(CH3)2OH, —CH(OH)CH(CH3)2, —C(CH3)2CH2OH, —CH2CH2SO2CH3, —CN, —CF3, —CHF2, —CO2H, —COCH3, —CO2CH2, —C(CH3)2CO2CH3, —CO2C(CH3)3, —COCH(OH) CH3, —COCH(CH3)2, —CONH2, —CONHCH3, —CON(CH3)2, —C(CH3)2CONH2, —NO2, —NH2, —NHCH3, —N(CH2)2, —NHCOCH3, —N(CH3)COCH3, —NHS(O)2CH2, —N(CH3)C(CH3)2CONH2, —N(CH3)CH2CH2S(O)2CH3, —OH, —OCH3, —S(O)2N (CH3)2, —SCH3, —CH2OCH3, —S(O)2CH3, cyclopropyl, oxetanyl, and morpholino, and preferably R1 is —H, —OH, —SH, —NH2, C1-C6alkyl, such as methyl, ethyl, propyl or butyl, C1-C6alkylamino such as methylamino, ethylamino, propylamino or butylamino, C1-C6alkoxy such as methoxy, ethoxy, propoxy or butoxy, (C1-C6alkyl)-E-(C1-C6alkylene), wherein E is —O— or —NH—, such as —CH2—NH—C2H5, —CH2—O—C2H5, —(CH2)2—NH—CH3, or —(CH2)2—O—CH3, or
• A is a carbon atom and R2 and R3 independently from each other are H, OH, SH, NH2, CF3, halogen, C1-C10alkyl, C1-C10alkylamino, C1-C10dialkylamino, C1-C10alkoxy, C1-C10alkoxy-C1-C10 alkylamino, C1-C10alkoxy-C1-C10alkoxy, C1-C10alkoxy-C5-C7heterocycle, C1-C10alkyamino-C5-C7heterocycle, —NH—SO2—C1-C6alkyl, —C(O)—C1-C6alkyl, —O—C(O)—C1-C6alkyl, —C(O)—C1-C10alkylamino, —C(O)—C1-C10dialkylamino, C5-C10aryl, C5-C9heterocyclyl, C3-C9 carbocyclyl, C1-C10alkylamino-C2-C7heterocycle, (C1-C6alkoxy)-E-(C1-C6alkylene) and preferably R1 is —H, —OH, —SH, —NH2, C1-C6alkyl, such as methyl, ethyl, propyl or butyl, C1-C6alkylamino such as methylamino, ethylamino, propylamino or butylamino, C1-C6alkoxy such as methoxy, ethoxy, propoxy or butoxy, (C1-C6alkyl)-E-(C1-C6alkylene), wherein E is —O— or —NH—, such as —CH2—NH—C2H5, —CH2—O—C2H5, —(CH2)2—NH—CH3, or —(CH2)2—O—CH3, more preferably R1 is —OH, and
• s is an integer from 1 to 4;
• X is an unbranched —(C1-C6 alkylene)-, —(C6-C20arylene)-, —(C4-C20heteroarylene)-, —(C1-C6 alkylene)-E-(C1-C6 alkylene)-, —(C1-C6 alkylene)-(C3-C7-carbocyclylene)-, —(C1-C6 alkylene)-(C3-C7-heterocyclylene)-, —(C1-C6 alkylene) —(C6-C20 arylene)-, —(C1-C6 alkylene) —(C4-C20 heteroarylene)-, —(C1-C6 alkylene)-E-(C1-C7 carbocyclylene)-, —(C1-C6 alkylene)-E-(C3-C7-heterocyclylene)-, —(C1-C6 alkylene)-E-(C6-C20 arylene)-, —(C1-C6 alkylene)-E-(C4-C20 heteroarylene)-, where alkylene, carbocyclylene, heterocyclylene, arylene, and heteroarylene are optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CH3, —CH2CH3, CH2CH(CH3)2, —CH2OH, —CH2CH2OH, —C(CH3)2OH, —CH(OH)CH(CH3)2, —C(CH3)2CH2OH, —CH2CH2SO2CH3, —CN, —CF3, —CHF2, —CO2H, —COCH3, —CO2CH3, —C(CH3)2CO2CH3, —CO2C(CH3)3, —COCH(OH) CH3, —COCH(CH3)2, —CONH2, —CONHCH3, —CON(CH3)2, —C(CH3)2CONH2, —NO2, —NH2, —NHCH3, —N(CH3)2, —NHCOCH3, —N(CH3) COCH3, —NHS(O)2CH3, —N(CH3)C(CH3)2CONH2, —N(CH3)CH2CH2S(O)2CH3, —OH, —OCH3, —S(O)2N (CH3)2, —SCH3, —CH2OCH3, S(O)2CH3, cyclopropyl, oxetanyl, and morpholino, and E is as defined above;
• Y is a single bond, —O—, —S—, —N(R12)—, —C(O)—, or —S(O)2— and R12 is as defined above;
• Z—R4 is a TLR2 agonist selected from the group consisting of:
• wherein:
• R5 and R6, identical or different, are the specific side chain of an amino acid;
• W is —O—, —NH—, or —S—;
• j and 1, identical or different, are 0 or 1;
• p is integer from 0 to 6;
• f, g, k, m, n, o, and q, identical or different, are integers from 1 to 4;
• r and t, identical or different, are integers from 1 to 6;
• and
• R4 is a lipid of Formula XI:
• wherein:
• R7 and R8 are independently from each other H, C1-C30alkyl, C2-C30alkylenyl, —C(O)—C1-C30alkyl, —C(O)—C2-C30alkylenyl, or —C(O)—O—C1-C30alkyl;
• R9 is H, C1-C30alkyl or C2-C30alkylenyl;
• R10 is H, C1-C30alkyl or C2-C30alkylenyl;
• R9 and R10 are not both H;
• L1 is absent, —OC(O)—, —O—, —NR11C(O)—, —OC(O)NR11— or —CH2- wherein R11 is H, C1-C30alkyl or C2-C30alkylenyl;
• L2 is —CH2OC(O)—, —CH2O—, —CH2NR11C(O)— or —CH2—, if L1 is absent L2 is —OC(O)—, —O—, —NR11C(O)—, —NR10R11, —OC(O)NR11— or —CH2- wherein R11 is as defined above.