Chimeric small molecules for the recruitment of antibodies to cancer cells

A compound for use in the treatment of prostate cancer in a patient according to the chemical structure:

• Wherein n is independently 1 or 2;
• A is an antibody binding moiety according to the chemical structure:
• Where Y′ is H or NO2;
• X is O, CH2, NR1, S(O), S(O)2, —S(O)2O, —OS(O)2, or OS(O)2O;
• R1 is H, a C1-C3 alkyl group, or a —C(O)(C1-C3) group;
• X′ is CH2, O, N—R1′ or S;
• R1′ is H or a C1-C3 alkyl;
• Z is a bond, a monosaccharide, disaccharide, oligosaccharide, glycoprotein or glycolipid;
• Xb is a bond, O, CH2, NR1 or S;
• B is a cell binding moiety according to the chemical formula:
• Where X1 and X2 are each independently CH2, O, NH or S;
• X3 is O, CH2, NR1, S(O), S(O)2, —S(O)2O, —OS(O)2, or OS(O)2O;
• R1 is H, a C1-C3 alkyl group, or a —C(O)(C1-C3) group;
• k is an integer from 1 to 15;
• L is a linker according to the chemical formula:
• Or L is a polyethylene glycol, polypropylene glycol or polypropylene-co-polyethylene glycol linker having between 1 and 20 glycol units;
• Where Ra is H, C1-C3 alkyl or alkanol or forms a proline side chain with R3;
• R3 forms a proline side chain with Ra or is a side chain derived from an amino acid selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tryptophan and valine;
• and
• Each m is independently an integer from 1 to 30;
• or
• L is a linker according to the chemical formula:
• Where Z and Z′ are each independently a bond, —(CH2)i—O, —(CH2)i—S, —(CH2)i—N—R,
• wherein said —(CH2)i group, if present in Z or Z′, is bonded to [CON], antibody binding terminus (ABT) or cell binding terminus (CBT);
• Each R is independently H, or a C1-C3 alkyl or alkanol group;
• Each R2 is independently H or a C1-C3 alkyl group;
• Each Y is independently a bond, O, S or N—R;
• Each i is independently an integer from 0 to 100;
• D is
• or a bond,
• with the proviso that Z, Z′ and D are not each simultaneously bonds;
• j is an integer from 1 to 100;
• m′ is an integer from 1 to 100;
• n′ is an integer from 1 to 100;
• and
• X″ is O, S or N—R,
• R is as defined above;
• and
• [CON] is a bond or a moiety according to the chemical structure:
• Where X2 is O, S, NR4, S(O), S(O)2, —S(O)2, —OS(O)2, or OS(O)2O;
• X3 is NR4, O or S;
• and R4 is H, a C1-C3 alkyl or alkanol group, or a —C(O)(C1-C3) group;
• or
• a pharmaceutically acceptable salt thereof.