US2019015378A1PendingUtilityA1

Compounds, compositions, and methods for the treatment of cancers

Assignee: PLACON THERAPEUTICS INCPriority: Dec 19, 2012Filed: Sep 19, 2018Published: Jan 17, 2019
Est. expiryDec 19, 2032(~6.4 yrs left)· nominal 20-yr term from priority
A61K 47/34A61K 9/5153A61P 35/00C07F 15/0093A61K 47/26A61K 31/282A61K 9/0019A61K 9/08Y10T428/298
63
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Claims

Abstract

The present teachings relate to compounds and compositions for treatment of cancers. In some embodiments, the composition comprises a platinum (IV) complex having at least one carboxylate or carbamate ligand.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A compound of Formula I, 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         two of R 1 , R 2 , R 3 , and R 4  each is a halide; 
         the remaining two of R 1 , R 2 , R 3 , and R 4  each is independently ammonia or an amine; and 
         R 5  and R 6  each independently is hydrogen, R 7 , or 
       
       
         
           
           
               
               
           
         
         
           wherein: 
           X is absent, C(R 8 ) 2 , O, S, or NR 8 , and 
           R 7  and R 8  independently at each occurrence is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups optionally is substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, ester, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl, phosphono, phosphate, sulfide, sulfinyl, sulfino, sulfonyl, sulfo, and sulfonamide, wherein each of the ester, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl, phosphono, phosphate, sulfide, sulfinyl, sulfino, sulfonyl, sulfo, and sulfonamide is optionally substituted with one or more suitable substituents. 
         
       
     
     
         2 . The compound of  claim 1 , wherein two of R 1 , R 2 , R 3 , and R 4  each is a halide. 
     
     
         3 . The compound of  claim 1 , wherein two of R 1 , R 2 , R 3 , and R 4  each is Cl. 
     
     
         4 . The compound of  claim 1 , wherein the remaining two of R 1 , R 2 , R 3 , and R 4  each is ammonia. 
     
     
         5 . The compound of  claim 1 , wherein at least one of the remaining two of R 1 , R 2 , R 3 , and R 4  is an amine. 
     
     
         6 . The compound of  claim 1 , wherein the remaining two of R 1 , R 2 , R 3 , and R 4  joined together form a diamine. 
     
     
         7 . The compound of  claim 1 , wherein the remaining two of R 1 , R 2 , R 3 , and R 4  joined together form cyclohexane-1,2-diamine. 
     
     
         8 . The compound of  claim 1 , wherein at least one of R 5  and R 6  is 
       
         
           
           
               
               
           
         
       
       and X is C(R 8 ) 2 . 
     
     
         9 . The compound of  claim 1 , wherein R 5  and R 6  are different. 
     
     
         10 . The compound of  claim 1 , wherein at least one of R 5  and R 6  is 
       
         
           
           
               
               
           
         
       
       and X is NR 8 . 
     
     
         11 . The compound of  claim 1 , wherein R 7  is alkyl or cycloalkyl. 
     
     
         12 . The compound of  claim 1 , wherein R 7  is alkyl optionally substituted with one or more groups each independently selected from halogen, hydroxyl, ester, alkoxy, aryloxy, amino, amide, aryl, arylalkyl, cycloalkyl, heteroaryl, and heterocyclyl, wherein each of ester, alkoxy, aryloxy, amino, amide, aryl, arylalkyl, cycloalkyl, heteroaryl, and heterocyclyl optionally is substituted with one or more suitable substituents. 
     
     
         13 . The compound of  claim 12 , wherein R 7  is alkyl optionally substituted with one or more groups each independently selected from halogen, hydroxyl, alkoxy, aryloxy, arylalkoxy, amino, amide, and aryl, wherein each of alkoxy, aryloxy, arylalkoxy, amino, amide, and aryl optionally is substituted with one or more substituents, each independently selected from one or more suitable substituents. 
     
     
         14 . The compound of  claim 13 , wherein R 7  is alkyl optionally substituted with one or more groups each independently selected from F, Cl, phenyl, benzyloxy, t-butylphenyl, amino, and bistrifluoromethylphenyl. 
     
     
         15 . The compound of  claim 1 , wherein at least one of R 5  and R 6  is R 7 . 
     
     
         16 . The compound of  claim 1 , wherein R 7  is a monocycloalkyl, a bicycloalkyl, or a tricycloalkyl. 
     
     
         17 . The compound of  claim 16 , wherein R 7  is cycloheptyl, cyclooctyl, cyclopentyl, cyclodecanyl, cycloundecanyl, cyclododecanyl, or adamantyl. 
     
     
         18 . A compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         19 . A pharmaceutical composition comprising a compound according to  claim 1 . 
     
     
         20 . The pharmaceutical composition of  claim 19  comprising a particle. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the particle comprises polyester. 
     
     
         22 . The pharmaceutical composition of  claim 19  comprising a surfactant. 
     
     
         23 . The pharmaceutical composition of  claim 19  comprising a lyoprotectant. 
     
     
         24 . The pharmaceutical composition of  claim 19 , wherein less than 50% of the compound is released in the first hour. 
     
     
         25 . A method of treating cancer selected from lung cancer, breast cancer, colorectal cancer, ovarian cancer, bladder cancer, prostate cancer, cervical cancer, renal cancer, leukemia, central nervous system cancers, myeloma, and melanoma, comprising administering a therapeutically effective amount of a compound of  claim 1 . 
     
     
         26 . A method of inhibiting proliferation of a cell comprising contacting the cell with an effective amount of a compound of  claim 1 . 
     
     
         27 . The method of  claim 26 , wherein the cell is a cancer cell.

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