USRE38117EExpiredUtility

Trioxane dimer compound having antiproliferative and antitumor activities

72
Assignee: HAUSER INCPriority: Jun 29, 1995Filed: Nov 21, 2000Granted: May 6, 2003
Est. expiryJun 29, 2015(expired)· nominal 20-yr term from priority
Inventors:Qun ZhengChristopher K. MurrayRandall J. DaughenbaughPoonsakdi PloypradithGary H. Posner
C07D 519/00A61K 47/55
72
PatentIndex Score
5
Cited by
6
References
23
Claims

Abstract

Described herein are novel trioxane dimers of structure which possess antiproliferative and antitumor activities.

Claims

exact text as granted — not AI-modified
The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:  
     
       1. A trioxane dimer compound having antiproliferative and antitumor activities of the formula:                    
       or an enantiomers  enantiomer thereof, wherein: 
       R 1  is CH 3 , PhCH 2 Cl  PhCH( Cl ), ( PhCH   2 —) or PhCl 2 ; and  
       R is a linker when T is CH 2 O; or  
       R is oxygen when T is CH 2 .  
     
     
       2. A compound according to  claim 1  wherein T is CH 2 O and said R is arylene, hetero-arylene, lower alkylene, lower alkenylene, a bivalent phosphate group, sulfur, oxygen, —(CH 2 CH 2 O) n — wherein n is 1-20 or —CH 2 CH 2 —(XCH 2 CH 2 ) n — where X is O, S or NY where Y is H (hydrogen) or alkyl and n is 0-20, or R is —W—Z—W— where W is a bivalent ester, carbamate or carbonate species and Z is arylene, polyethylene glycol (PEG), hetero-arylene, lower alkylene, or lower alkenylene, and R 1  is hydrogen,  a methyl group, chloromethylphenyl  phenylchloromethyl (PhCH 2 )  ( PhCH ( Cl )), dichlorophenyl (PhCl 2 ) or a benzyl group (PhCH 2 ) or when T is a CH 2  group,  and R is oxygen, then and  R 1  is hydrogen,  a methyl group, chloromethylphenyl (PhCH 2 Cl)  phenylchloromethyl ( PhCH ( Cl )), dichlorophenyl (PhCl 2 ) or a benzyl group (PhCH 2 ). 
     
     
       3. A compound according to  claim 1 , wherein said R is (CH 2 CH 2 O) n  and n is 1-20. 
     
     
       4. A compound according to  claim 3 , wherein n is 2. 
     
     
       5. A compound according to  claim 3 , wherein n is 3. 
     
     
       6. A compound according to  claim 3 , wherein n is 6. 
     
     
       7. A compound according to  claim 1 , wherein said R is selected from the group consisting of:                  
                   
     
     
       8. A compound according to  claim 1 , wherein T is CH 2 , and R is oxygen. 
     
     
       9. A compound according to  claim 1 , wherein T is CH 2 , R is oxygen and R 1  is a methyl group. 
     
     
       10. A compound according to  claim 1 , wherein T is CH 2 , R is oxygen and R 1  is chloromethylphenyl. 
     
     
       11. A trioxane dimer compound having antiproliferative and antitumor activities of the formula:                    
       or an enantiomer thereof, wherein: 
       R is arylene, hetero-arylene, lower alkylene, lower alkenylene, a bivalent phosphate species, sulfur oxygen —(CH 2 CH 2 O) n — wherein n is 1-20 or —CH 2 CH 2 — (XCH 2 CH 2 ) n — where X is O, S or NY where Y is H (hydrogen) or alkyl and n is 1-20, or R is —W—Z—W— where W is a bivalent ester, carbonate or carbonate species and Z is arylene, polyethylene glycol (PEG), hetero-arylene, lower alkylene, or lower alkenylene.  
     
     
       12. A compound according to  claim 11 , wherein R is                    
     
     
       13. A trioxane dimer compound having antiproliferative and antitumor activities of the formula:                    
       or an enantiomer thereof, wherein: 
       R 1  is H, CH 3 , PhCH 2 Cl or PhCl 2 ; and  
       R is a linker other than                    
        and T is CH 2 O; or  
       R is oxygen when T is CH 2 .  
     
     
       14. A compound according to claim  13   22 wherein T is CH 2 O and said R is arylene, hetero-arylene, lower alkylene, lower alkenylene, a bivalent phosphate species, sulfur, oxygen, —(CH 2 CH 2 O) n — wherein n is 1-20 or —CH 2 CH 2 — (XCH 2 CH 2 ) n — where X is O, S or NY where Y is H (hydrogen) or alkyl and n is 1-20, or R is —W—Z—W— where W is a bivalent ester, carbamate or carbonate species and Z is arylene, polyethylene glycol (PEG), hetero-arylene, lower alkylene, or lower alkenylene, and R 1  is hydrogen, a methyl group, chloromethylphenyl (PhCH 2 Cl)  phenylchloromethyl ( PhCH ( Cl )), dichlorophenyl (PhCl 2 ) or a benzyl group (PhCH 2 ) or when T is a CH 2  group,and R is oxygen and, then R 1  is hydrogen, a methyl group, chloromethylphenyl (PhCH 2 Cl)  phenylchloromethyl ( PhCH ( Cl ), dichlorophenyl (PhCl 2 ) or a benzyl group (PhCH 2 ). 
     
     
       15. A compound according to  claim 14 , wherein said R is (CH 2 CH 2 O), and n is 1-20. 
     
     
       16. A compound according to  claim 15 , where n is 2. 
     
     
       17. A compound according to  claim 15 , where n is 3. 
     
     
       18. A compound according to  claim 15 , where n is 6. 
     
     
       19. A compound according to claim  13   22 , wherein T is CH 2 , R is oxygen and R 1  is hydrogen. 
     
     
       20. A compound according to claim  13   22 , wherein T is CH 2 , R is oxygen and R 1  is a methyl group. 
     
     
       21. A compound according to claim  13   22 , wherein T is CH 2 , R is oxygen and R 1  is chloromethylphenyl  phenylchloromethyl. 
     
     
       22. A trioxane dimer compound having antiproliferative and antitumor activities of the formula:                    
       or an enantiomer thereof, wherein: 
       R 1  is H, CH 3 , PhCH( Cl ) , PhCH   2 , PhCl 2 ; and  
       T is CH 2 O when R is a linker other than                    
       or 
       R is oxygen when T is CH 2 .  
     
     
       23. A compound according to  claim 22 , wherein said R is selected from the group consisting of:

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