Novel compounds useful for modulating abnormal cell proliferation

• US 20060058297A1
• Filed: 09/14/2004
• Published: 03/16/2006
• Est. Priority Date: 09/14/2004
• Status: Active Grant

• Current Assignee: Hospital For SICK Children
• Original Assignee: Hospital For SICK Children
• Inventors: Rounova, Olga, Demin, Peter, Grunberger, Tom, Roifman, Chaim
• Granted Patent: US 7,807,719 B2
• Time in Patent Office: Days
• US Class Current: 514/237.500
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07C 255/41 the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
• CPC Class Codes: C07D 213/40 Acylated substituent nitrogen atom
• CPC Class Codes: C07D 213/57 Nitriles
• CPC Class Codes: C07D 307/54 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/24 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

There is described compounds of Formulae I, II, III, IV and V. The compounds of Formulae I, II, III, IV and/or V are useful: in therapeutic methods and compositions for modulating cell proliferation, in diagnostic assays and as research tools.

Claims

1. A compound of Formula I, and salts, solvates and hydrates thereof:

20. A pharmaceutical composition comprising the compound defined in claim 1, together with a pharmaceutically acceptable carrier therefor.

21. A method of modulating cell proliferation comprising administering an effective amount of the compound defined in claim 1 to modulate cell proliferation to a cell or animal in need thereof.

22. A method of inhibiting cell proliferation comprising administering an effective amount of the compound defined in claim 1 to inhibit cell proliferation to a cell or animal in need thereof.

23. The method defined in claim 22, wherein the cell proliferation that is inhibited is cancer cell proliferation.

24. The method defined in claim 23, wherein the cancer cell is a hematopoietic cell

25. A method of treating cancer comprising administering to an animal in need thereof an effective amount of the compound defined in claim 1.

26. The method defined in claim 25, wherein cancer comprises a hematopoietic cell.

27. The method defined in claim 23, wherein the cancer is a leukemia, a lymphoma or a myeloma.

28. The method defined in claim 27, wherein the leukemia is selected from the group comprising acute lymphoblastic leukemia, aggressive Philadelphia+ leukemia, acute myelocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia and juvenile myelomonocyte leukemia.

29. The method defined in claim 27, wherein the leukemia is acute lymphoblastic leukaemia.

30. A method of modulating cell proliferation comprising administering an effective amount of a compound capable of modulating cell proliferation according to any one of claims 1 or a composition according to claim 20 to a cell or animal in need thereof.

31. A method of inhibiting cell proliferation comprising administering an effective amount of a compound capable of inhibiting cell proliferation according to any one of claims 1 or a composition according to claim 20 to a cell or animal in need thereof.

32. A method of inhibiting cancer cell proliferation comprising administering an effective amount of a compound capable of inhibiting cancer cell proliferation according to any one of claims 1 or a composition according to claim 20 to a cell or animal in need thereof.

33. A method of treating cancer comprising administering an effective amount of a compound capable of inhibiting cancer cell proliferation according to any one of claims 1 or a composition according to claim 20 to a cell or animal in need thereof.

34. The method defined in claim 32, wherein the cancer is a hematopoietic cell cancer.

35. The method defined in claim 32, wherein the cancer is a leukemia, a lymphoma or a myeloma.

36. The method defined in claim 35, wherein the leukemia is selected from the group comprising acute lymphoblastic leukemia, aggressive Philadelphia+ leukemia, acute myelocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia or juvenile myelomonocyte leukaemia.

37. The method defined in claim 35, wherein the leukemia is is acute lymphoblastic leukemia.

38. Use of the compound defined in claim 1 to treat cancer.

2. 4-Chloro-2-cyano-5-phenyl-penta-2E,4Z-dienoic acid 3,4-dihydroxybenzylamide (CRC-47).

3. A compound of Formula II, and salts, solvates and hydrates thereof:

4. 2-Cyano-5-furan-2-yl-penta-2E,4E-dienoic acid 3,4-dihydroxybenzylamide (CRH-48)

5. 2-Cyano-5-pyridin-3-yl-penta-2E,4E-dienoic acid 3,4-dihydroxybenzylamide (CRH-58).

6. 2-Cyano-5-pyridin-3-yl-penta-2E,4E-dienoic acid benzylamide (CRH-59).

7. 2-Cyano-5-thiophen-2-yl-penta-2E,4E-dienoic acid 3,4-dihydroxybenzylamide (CRH-60).

8. A compound of Formula III, and salts, solvates and hydrates thereof:

9. 2-Cyano-5-(2,5-dihydroxyphenyl)penta-2E,4E-dienoic acid benzylamide (CRO-70).

10. 2-Cyano-5-(2-hydroxyphenyl)-penta-2E,4E-dienoic acid benzylamide (CRO-90).

11. 2-Cyano-5-(2-hydroxyphenyl)-penta-2E,4E-dienoic acid 3,4-dihydroxybenzyl-amide (CRO-91).

12. A compound of Formula IV, and salts, solvates and hydrates thereof:

13. 2-Cyano-N-pyridin-4-ylmethyl-3-(4-trans-styrylphenyl)-E-acrylamide (CRS-75).

14. 2-Cyano-N-(3,4-dihydroxybenzyl)-3-[4-(2-pyridin-4-yl-trans-vinyl)-phenyl]-E-acrylamide (CRS-76).

15. 2-Cyano-N-pyridin-4-ylmethyl-3-[4-(2-pyridin-4-yl-trans-vinyl)phenyl]-E-acrylamide (CRS-77).

16. A compound of Formula V, and salts, solvates and hydrates thereof:

17. 2-Cyano-7-(4-hydroxy-3-methoxyphenyl)hepta-2E,4E,6E-trienoic acid 3,4-di-hydroxybenzylamide (CRT-67).

18. 2-Cyano-7-(4-hydroxy-3-methoxyphenyl)hepta-2E,4E,6E-trienoic acid benzylamide (CRT-86).

19. 2-Cyano-7-(3,4-dihydroxyphenyl)hepta-2E,4E,6E-trienoic acid benzylamide (CRT-88).