Pharmaceutical compounds targeted by MIF affinity-tethered moieties

A pharmaceutical composition comprising a tether moiety of formula (1)

• wherein Q is selected from the group consisting of O, S, N(R9), and C(R9)R10;
• X is selected from the group consisting of nothing, O, S, N(R9), N(R9)N(R10), (CH2)k-(OCH2CH2)l, CR9R10-CR11R12, and C(O);
• Y is selected from the group consisting of nothing, O, S, N(R11), N(R11)N(R12), —NC(O), C(O)O—, C(O)N(R9)-, C(O)N(R9)N(R10)-, C(O)N(R9)N═, C(O)(CH2)m-S—, and C(O)(CH2)m-S—S—;
• R1, R2, R3, R4, R5, R6, R7 and R8 are each independently selected from the group consisting of H, hydroxyl, substituted C1-C8 alkyl, substituted C1-C8 alkyl, alkenyl, alkynyl, C1-C8 acyl, substituted C1-C8 acyl, C1-C8 alkoxy, substituted C1-C8 alkoxy, C1-C8 ester, substituted C1-C8 ester, (CH2)n-phenyl, substituted (CH2)n-phenyl, (CH2)n-heterocycle, substituted (CH2)n-heterocycle, halogen, cyano, nitro, amino, (CH2)n-monoalkylamine, substituted (CH2)n-monoalkylamine, (CH2)n-dialkylamine, substituted (CH2)n-dialkylamine, carboxylic acid, (CH2)n-dialkylamine, and substituted (CH2)n-alkylamide
• j, k, l, m and n are each integers independently from 1 to 8;
• Y is selected from the group consisting of nothing, O, S, N(R11), N(R11)N(R12), —NC(O), C(O)O—, C(O)N(R9)═, C(O)N(R9)N(R10), C(O)N(R9)N═, C(O)(CH2)m-S—, and C(O)(CH2)m-S—S—, and Z represents a drug or an imaging moiety.

A therapeutic compound comprising a compound from formula (1)

• wherein Q is selected from the group consisting of O, S, N(R9), and C(R9)R10;
• X is selected from the group consisting of nothing, O, S, N(R9), N(R9)N(R10), (CH2)k-(OCH2CH2)l, CR9R10-CR11R12, and C(O);
• Y is selected from the group consisting of nothing, O, S, N(R11), N(R11)N(R12), —N═, C(O), C(O)O—, C(O)N(R9)-, C(O)N(R9)N(R10)-, C(O)N(R9)N═, C(O)(CH2)m-S—, and C(O)(CH2)m-S—S—;
• R1, R2, R3, R4, R5, R6, R7 and R8 are each independently selected from the group consisting of H, hydroxyl, C1-C8 alkyl, alkenyl, alkynyl, substituted C1-C8 alkyl, alkenyl, alkynyl, C1-C8 acyl, substituted C1-C8 acyl, C1-C8 alkoxy, substituted C1-C8 alkoxy, C1-C8 ester, substituted C1-C8 ester, (CH2)n-phenyl, substituted (CH2)n-phenyl, (CH2)n-heterocycle, substituted (CH2)n-heterocycle, halogen, cyano, nitro, amino, (CH2)n-monoalkylamine, substituted (CH2)n-monoalkylamine, (CH2)n-dialkylamine, substituted (CH2)n-dialkylamine, carboxylic acid, (CH2)n-dialkylamine, (CH2)n-monoalkylamide, substituted (CH2)n-monoalkylamide, (CH2)n-dialkylamide, and substituted (CH2)n-dialkylamide;
• wherein the substitutions are selected from the group consisting of C1-C8 alkyl, C1-C8 alkenyl, halo-substituted aryl, aryl, hydroxyl, hydrogen, C1-C8 alkoxy, and combinations thereof
• R9, R10, R11, and R12 are each independently selected from the group consisting of H, hydroxyl, C1-C8 alkyl, substituted C1-C8 alkyl, alkenyl, alkynyl, (CH2)-phenyl, substituted (CH2)n-phenyl, (CH2)n-heterocycle, and substituted (CH2)n-heterocycle;
• wherein the substitutions are selected from the group consisting of C1-C8 alkyl, C1-C8 alkenyl, halo-substituted aryl, aryl, hydroxyl, hydrogen, C1-C8 alkoxy, and combinations thereof
• j, m, and n are each integers independently from 0 to 8, k is an integer from 0 to 2, l is an integer from 1 to 8;
• and Z represents a drug or an imaging moiety.