Chimeric small molecules for the recruitment of antibodies to cancer cells

1. A compound according to the chemical structure:

wherein A is a moiety according to the chemical formula:

Where Y′ is H or NO 2 ;

X is O, CH 2 , NR 1 , S(O), S(O) 2 , -S(O) 2 O, -OS(O) 2 , or OS(O) 2 O;

R 1 is H, a C 1 -C 3 alkyl group, or a -C(O)(C 1 -C 3 ) group;

X′ is CH 2 , O, N-R 1 or S;

R 1′ is H or C 1 -C 3 alkyl;

Z is a bond, a monosaccharide, disaccharide, oligosaccharide, glycoprotein or glycolipid; and

X b is a bond, O, CH 2 , NR 1 or S;

B is a cell binding moiety according to the chemical formula:

Where k is an integer from 1 to 6;

Each n is independently 1 or 2;

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 R a is H, C 1 -C 3 alkyl or alkanol or forms a proline side chain with R 3 ;

R 3 forms a proline side chain with R a or is a side chain derived from an amino acid wherein said amino acid is selected from the group consisting of a side chain 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 12; and

[CON] is a moiety according to the chemical structure:

or

a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein each n is 1.

3. The compound according to claim 1 wherein each n is 2.

4. The compound according to claim 1 wherein one n is 1 and the other n is 2.

5. The compound to claim 2 wherein k is 3, 4 or 5.

6. The compound according to claim 2 wherein k is 4.

7. The compound according to claim 2 wherein L is a polyethylene glycol linker having between 1 and 12 ethylene glycol units.

8. The compound according to claim 6 wherein said linker has between 1 and 8 ethylene glycol units.

9. The compound according to claim 7 wherein said linker has between 1 and 4 ethylene glycol units.

10. The compound according to claim 1 wherein A is a moiety according to the chemical formula:

Where Y′ is H or NO 2 ;

X is O, CH 2 , NR 1 , S(O), S(O) 2 , —S(O) 2 O, —OS(O) 2 , or OS(O) 2 O;

R 1 is H, a C 1 -C 3 alkyl group, or a —C(O)(C 1 -C 3 ) group;

X′ is CH 2 , O, N—R 1 ′ or S;

R 1′ is H or C 1 -C 3 alkyl;

Z is a bond, a monosaccharide, disaccharide, oligosaccharide, glycoprotein or glycolipid; and

X b is a bond, O, CH 2 , NR 1 or S.

11. The compound according to claim 10 wherein Y′ is H.

12. The compound according to claim 10 wherein A is

13. The compound according to claim 12 wherein X is NH.

14. The compound according to claim 10 wherein A is

15. The compound according to claim 14 wherein X′ is O or N—R 1 ′ and R 1 ′ is H.

16. The compound according to claim 15 wherein X′ is O.

17. The compound according to claim 14 wherein A is

18. The compound according to claim 14 wherein X is O and Z is a monosaccharide selected from the group consisting of aldoses, ketoses and aminosugars.

19. The compound according to claim 14 wherein Z is a monosaccharide selected from the group consisting of D-glyceraldehdye, D-erythrose, D-Threose, D-ribose, D-arabinose, D-xylose, D-lyxose, D-allose, D-altrose, D-Glucose, D-Mannose, D-gulose, D-idose, D-galactose, dihydroxyacetone, D-erythrulose, D-ribulose, D-xylulose, D-Psicose, D-Fructose, D-Sorbose, D-Tagatose, galactoseamine, sialic acid and N-acetylglucosamine.

20. The compound according to claim 14 wherein Z is a disaccharide selected from the group consisting of sucrose, which may be optionally N-acetylated, lactose, which may be optionally N-acetylated, maltose, which may be optionally N-acetylated, trehalose, which may be optionally N-acetylated, cellobiose, which may be optionally N-acetylated, kojibiose, which may be optionally N-acetylated, nigerose, which may be optionally N-acetylated, isomaltose, which may be optionally N-acetylated, β,β-trehalose, which may be optionally N-acetylated, sophorose, which may be optionally N-acetylated, laminaribiose, which may be optionally N-acetylated, gentiobiose, which may be optionally N-acetylated, turanose, which may be optionally N-acetylated, maltulose, which may be optionally N-acetylated, palatinose, which may be optionally N-acetylated, mannobiose, which may be optionally N-acetylated, melibiose, which may be optionally N-acetylated, melibiulose, which may be optionally N-acetylated, rutinose, which may be optionally N-acetylated, rutinulose, which may be optionally N-acetylated and xylobiose, which may be optionally N-acetylated.

21. A pharmaceutical composition comprising an effective amount of a chimeric compound according to claim 1 in combination with a pharmaceutically acceptable carrier, additive or excipient.

22. The composition according to claim 21 wherein said composition further comprises an effective amount of an additional anticancer agent.

23. The composition according to claim 22 wherein said additional anticancer agent is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent, a microtubule inhibitor or mixtures thereof.

24. The composition according to claim 21 in parenteral dosage form.

25. The composition according to claim 24 wherein said parenteral dosage form is an intravenous dosage form.