USRE38506EExpiredUtility

Potent inducers of terminal differentiation and methods of use thereof

96
Assignee: SLOAN KETTERING INST CANCERPriority: Oct 4, 1991Filed: Nov 2, 2001Granted: Apr 20, 2004
Est. expiryOct 4, 2011(expired)· nominal 20-yr term from priority
C07C 233/06C07C 259/06C07D 295/185C07D 277/46C07C 233/05C07D 213/75C07C 233/25C07C 255/60C07C 233/15C07C 2601/14C07C 255/42C07D 211/32
96
PatentIndex Score
53
Cited by
69
References
24
Claims

Abstract

The present invention provides the compound having the structure: wherein each of R 1 and R 2 are independently the same as or different from each other; when R 1 and R 2 are the same, each is a substituted or unsubstituted arylamino, cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiozoleamino group; when R 1 and R 2 are different, R 1 =R 3 —N—R 4 , wherein each of R 3 and R 4 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 R 3 and R 4 bond together to form a piperidine group and R 2 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.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
       1. A compound having the structure:                    
       wherein each of R 1  and R 2  are independently the same as or different from each other; when R 1  and R 2  are the same, each is and are a substituted or unsubstituted cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiazoleamino group; when R 1  and R 2  are different, R 1 =R 3 —N—R 4 , wherein each of R 3  and R 4  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 R 3  and R 4  bond together to form a piperidine group and R 2  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 R 3  and R 4  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 R 3  and R 4  bond together to form a piperidine group; R 2  is a hydroxylamino, hydroxyl, amino, alkylamino, or alkyloxy group; and n is an integer from about 4  5 to about 8 7 ; and R 3   —N—R   4    and R   2    are different.   
     
     
       3. A compound of  claim 2 , wherein R 2  is a hydroxylamino, hydroxyl, amino, methylamino, or methoxy group and n is 6. 
     
     
       4. A compound of  claim 3 , wherein R 4  is a hydrogen atom and R 3  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 R 4  is a hydrogen atom and R 3  is a cyclohexyl group. 
     
     
       7. A compound of  claim 3 , wherein R 4  is a hydrogen atom and R 3  is a methyoxy methoxy group. 
     
     
       8. A compound of  claim 3 , wherein R 3  and R 4  bond together to form a piperidine group. 
     
     
       9. A compound of  claim 3 , wherein R 4  is a hydrogen atom and R 3  is a hydroxyl group. 
     
     
       10. A compound of  claim 3 , wherein R 4  is a hydrogen atom and R 3  is a benzyloxy group. 
     
     
       11. A compound of claim  3   2 , wherein R 4  is a hydrogen atom and R 3  is a δ-pyridine γ-pyridine group. 
     
     
       12. A compound of claim  3   2 , wherein R 4  is a hydrogen atom and R 3  is a β-pyridine group. 
     
     
       13. A compound of claim  3   2 , wherein R 4  is a hydrogen atom and R 3  is a α-pyridine group. 
     
     
       14. A compound of  claim 3 , wherein R 3  and R 4  are both methyl groups. 
     
     
       15. A compound of  claim 3 , wherein R 4  is a methyl group and R 3  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 .

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