Claims for Patent: RE38506

Summary for Patent: RE38506

Title:	Potent inducers of terminal differentiation and methods of use thereof
Abstract:	The present invention provides the compound having the structure: wherein each of R1 and R2 are independently the same as or different from each other; when R1 and R2 are the same, each is a substituted or unsubstituted arylamino, cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiozoleamino group; when R1 and R2 are different, R1=R3—N—R4, wherein each of R3 and R4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R3 and R4 bond together to form a piperidine group and R2 is a hydroxylamino, hydroxyl, amino, alkylamino, dialkylamino or alkyloxy group; and n is an integer from about 4 to about 8. The present invention also provides a method of selectively inducing terminal differentiation of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition and a therapeutically acceptable amount of the compound above.
Inventor(s):	Ronald Breslow, Paul A. Marks, Richard A. Rifkind, Branko Jursic
Assignee:	Columbia University in the City of New York, Memorial Sloan Kettering Cancer Center
Application Number:	US10/004,411
Patent Claims:	1. A compound having the structure: wherein each of R1 and R2 are independently the same as or different from each other; when R1 and R2 are the same, each is and are a substituted or unsubstituted cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiazoleamino group; when R1 and R2 are different, R1=R3—N—R4, wherein each of R3 and R4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R3 and R4 bond together to form a piperidine group and R2 is a hydroxylamino, hydroxyl, amino, alkylamino, or alkyloxy group; and n is an integer from about 4 to about 8. 2. A compound of claim 1 having the structure: wherein each of R3 and R4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R3 and R4 bond together to form a piperidine group; R2 is a hydroxylamino, hydroxyl, amino, alkylamino, or alkyloxy group; and n is an integer from about 4 5to about 87; and R3 —N—R 4 and R 2 are different. 3. A compound of claim 2, wherein R2 is a hydroxylamino, hydroxyl, amino, methylamino, or methoxy group and n is 6. 4. A compound of claim 3, wherein R4 is a hydrogen atom and R3 is a substituted or unsubstituted phenyl group. 5. A compound of claim 4, wherein the phenyl group is substituted with a methyl, cyano, nitro, trifluoromethyl, amino, aminocarbonyl, metylcyano, chloro, fluoro, bromo, iodo, 2,3-difluoro, 2,4-difluoro, 2,5-difluoro, 3,4-difluoro, 3,5-difluoro, 2,6-difluoro, 1,2,3-trifluoro, 2,3,6-trifluoro, 2,4,6-trifluoro, 3,4,5-trifluoro, 2,3,5,6-tetrafluoro, 2,3,4,5,6-pentafluoro, azido, hexyl, t-butyl, phenyl, carboxyl, hydroxyl, methyoxy methoxy, phenyloxy, benzyloxy, phenylaminooxy, phenylaminocarbonyl, methyoxycarbonyl methoxycarbonyl, methylaminocarbonyl, dimethylamino, dimethylaminocarbonyl, or hydroxylaminocarbonyl group. 6. A compound of claim 3, wherein R4 is a hydrogen atom and R3 is a cyclohexyl group. 7. A compound of claim 3, wherein R4 is a hydrogen atom and R3 is a methyoxy methoxy group. 8. A compound of claim 3, wherein R3 and R4 bond together to form a piperidine group. 9. A compound of claim 3, wherein R4 is a hydrogen atom and R3 is a hydroxyl group. 10. A compound of claim 3, wherein R4 is a hydrogen atom and R3 is a benzyloxy group. 11. A compound of claim 3 2, wherein R4 is a hydrogen atom and R3 is a δ-pyridine γ-pyridine group. 12. A compound of claim 3 2, wherein R4 is a hydrogen atom and R3 is a β-pyridine group. 13. A compound of claim 3 2, wherein R4 is a hydrogen atom and R3 is a α-pyridine group. 14. A compound of claim 3, wherein R3 and R4 are both methyl groups. 15. A compound of claim 3, wherein R4 is a methyl group and R3 is a phenyl group. 16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 2. 17. A pharmaceutical composition of claim 16 in combination with an antitumor agent. 18. A compound having the structure: wherein n is an integer selected from the group consisting of 5, 6, 7 and 8. 19. A pharmaceutical composition comprising a therapeutically effective amount of a compound having the structure: wherein n is an integer selected from the group consisting of 5, 6, 7 and 8: and a pharmaceutically acceptable carrier. 20. A compound having the structure: 21. A pharmaceutical composition comprising a therapeutically effective amount of a compound having the structure: and a pharmaceutically acceptable carrier. 22. A compound having the structure: 23. A pharmaceutical composition comprising a compound having the structure: and a pharmaceutically acceptable carrier. 24. A compound having the structure: wherein R 3 is hydrogen and R 4 cycloalkyl, aryl, aryloxy, arylalkloxy, or pyridine group, or R 3 and R 4 bond together to form a piperidine group; R 2 is a hydroxylamino group; and n is an integer selected from the group consisting of 5, 6, 7 and 8.