Alkyl chain modified imidazoquinoline tlr7/8 agonist compounds and uses thereof

A method of stimulating an immune response in a mammalian subject in need thereof, comprising administering to the mammalian subject a pharmaceutical composition in an amount sufficient to stimulate the immune response in the mammalian subject,

• the pharmaceutical composition comprising (i) a compound of formula (J), or a salt thereof, and (ii) a pharmaceutically acceptable excipient, wherein the compound of formula (J) has the following structure:
• wherein:
• R0 is —(CH2)z(C(CH3)2)RA or —(CH2)mRA;
• m is 0, 1, 2, or 3;
• z is 1 or 2;
• RA is C3-C8 cycloalkyl optionally substituted by 1 to 4 groups independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkylene, and halogen;
• X is —NH—;
• R1 is C3-C6 alkyl, —(CH2)pOR1a, —(CH2)pNHR1b or —(CH2)pR1c;
• where R1a and R1b are independently C1-C3 alkyl;
• R1c is C3-C4 cycloalkyl;
• and p is 1 or 2;
• R2 is NHR2a;
• where R2a is H, OH, NH2, or methyl;
• each R3 is independently halogen, C1-C8 alkyl, —(C1-C7 alkylene)-NH2, or —CH2-phenylene-CH2NH2;
• q is 0, 1, 2, 3, or 4;
• and
• R4a and R4b are independently H or C1-C8 alkyl.

A method of inducing an antigen-specific antibody response in a mammalian subject in need thereof, comprising administering to the mammalian subject a pharmaceutical composition in an amount sufficient to induce the antigen-specific antibody response and/or an antigen-specific T cell response in the mammalian subject,

• the pharmaceutical composition comprising (i) a compound of formula (J), or a salt thereof, and (ii) a pharmaceutically acceptable excipient, wherein the compound of formula (J) has the following structure:
• wherein:
• R0 is —(CH2)z(C(CH3)2)RA or —(CH2)mRA;
• m is 0, 1, 2, or 3;
• z is 1 or 2;
• RA is C3-C8 cycloalkyl optionally substituted by 1 to 4 groups independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkylene, and halogen;
• X is —NH—;
• R1 is C3-C6 alkyl, —(CH2)pOR1a, —(CH2)pNHR1b or —(CH2)pR1c;
• where R1a and R1b are independently C1-C3 alkyl;
• R1c is C3-C4 cycloalkyl;
• and p is 1 or 2;
• R2 is NHR2a;
• where R2a is H, OH, NH2, or methyl;
• each R3 is independently halogen, C1-C8 alkyl, —(C1-C7 alkylene)-NH2, or —CH2-phenylene-CH2NH2;
• q is 0, 1, 2, 3, or 4;
• and
• R4a and R4b are independently H or C1-C8 alkyl.