US2018153830A1PendingUtilityA1

Selective inhibitors of undifferentiated cells

Assignee: YISSUM RES DEV CO OF HEBREW UNIV JERUSALEM LTDPriority: May 22, 2012Filed: Feb 1, 2018Published: Jun 7, 2018
Est. expiryMay 22, 2032(~5.8 yrs left)· nominal 20-yr term from priority
A61K 31/513A61K 31/341A61K 31/15A61K 31/4453A61K 31/451A61K 31/4545A61K 31/343A61K 31/404A61K 31/4409A61K 31/34G01N 33/5073A61K 31/381A61P 35/00A61K 31/136G01N 33/502G01N 2500/10A61K 31/4015A61K 31/403A61K 31/4985A61P 43/00A61K 31/166A61K 31/165A61K 31/155A61P 35/02G01N 2500/02A61K 31/407
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Claims

Abstract

Uses of a compound of any of Formulas I-VI as a cytotoxic inhibitor of undifferentiated cells are disclosed herein, as well as pharmaceutical compositions comprising a compound of any of Formulas I-VI, and methods for identifying a lead candidate for inhibiting undifferentiated cells. Further disclosed are uses of an SCD-1 inhibitor as a cytotoxic inhibitor of undifferentiated cells.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of inhibiting undifferentiated cells, the method being effected by contacting undifferentiated cells with a compound selected from the group consisting of:
 a compound of Formula I   
       
         
           
           
               
               
           
         
         a compound of Formula II 
       
       
         
           
           
               
               
           
         
         a compound of Formula III 
       
       
         
           
           
               
               
           
         
         a compound of Formula IV 
       
       
         
           
           
               
               
           
         
         a compound of Formula V 
       
       
         
           
           
               
               
           
         
         and 
         a compound of Formula VI 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is hydrogen, and 
         R 2  is selected from the group consisting of:
 hydrogen, 
 2,4-dioxo-5-fluoropyrimidin-1-ylcarbonyl, 
 2-methylbenzofuran-3-ylmethyleneamino, 
 and 
 —NH—R 5 , wherein R 5  is selected from the group consisting of:
 pyridinylcarbonyl, 
 2-hydroxyl-2-phenyl-2-thiophen-2-yl-acetyl, 
 (C 1-6 )alkyl-carbonyl, 
 N-(ethoxycarbonylmethyl)-2,4-dioxo-pyrrolidine-3-ylidene-methyl, 
 naphthylsulfonyl, and 
 N-hydroxy-acetimidoyl; 
 
 
         or wherein: 
         R 1  is benzoyl and R 2  is 4-chlorobenzamido; and 
         R 3  and R 4  are independently selected from the group consisting of hydrogen, halo, NH 2 , biphenyloxymethyl and (C 1-4 )alkyl, 
         with the proviso that at least one of R 1 , R 2 , R 3  and R 4  is not hydrogen, halo, NH 2  or (C 1-4 )alkyl. 
       
     
     
         2 . The method of  claim 1 , wherein said compound is of Formula I. 
     
     
         3 . The method of  claim 2 , wherein:
 R 1  is hydrogen, and   R 2  is selected from the group consisting of:
 2,4-dioxo-5-fluoropyrimidin-1-ylcarbonyl, 
 2-methylbenzofuran-3-ylmethyleneamino, and 
 —NH—R 5 , wherein R 5  is selected from the group consisting of:
 pyridinylcarbonyl, 
 2-hydroxyl-2-phenyl-2-thiophen-2-yl-acetyl, 
 (C 1-6 )alkyl-carbonyl, 
 N-(ethoxycarbonylmethyl)-2,4-dioxo-pyrrolidine-3-ylidene-methyl, 
 naphthylsulfonyl, and 
 N-hydroxy-acetimidoyl; 
 
   or wherein:   R 1  is benzoyl and R 2  is 4-chlorobenzamido; and   R 3  and R 4  are independently selected from the group consisting of hydrogen, chloro, NH 2 , and methyl.   
     
     
         4 . The method of  claim 1 , wherein said compound is of formula II: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 1 , wherein said compound is of formula III: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 1 , wherein said compound is of formula IV: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method of  claim 1 , wherein said compound is of formula V: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 1 , wherein said compound is of formula VI: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 1 , wherein said undifferentiated cells comprise pluripotent stem cells. 
     
     
         10 . The method of  claim 1 , wherein said undifferentiated cells comprise undifferentiated cancer cells. 
     
     
         11 . The method of  claim 10 , wherein said undifferentiated cancer cells comprise cancer stem cells and/or Grade 4 undifferentiated cancer cells. 
     
     
         12 . A method of treating a proliferative disease or disorder associated with proliferation of undifferentiated cells in a subject in need thereof, said undifferentiated cells being selected from the group consisting of pluripotent stem cells, cancer stem cells and Grade 4 undifferentiated cancer cells, the method comprising administering to the subject a therapeutically effective amount of a compound selected from the group consisting of:
 a compound of Formula I   
       
         
           
           
               
               
           
         
         a compound of Formula II 
       
       
         
           
           
               
               
           
         
         a compound of Formula III 
       
       
         
           
           
               
               
           
         
         a compound of Formula IV 
       
       
         
           
           
               
               
           
         
         a compound of Formula V 
       
       
         
           
           
               
               
           
         
         and 
         a compound of Formula VI 
       
       
         
           
           
               
               
           
         
         thereby treating the proliferative disease or disorder. 
       
     
     
         13 . The method of  claim 12 , wherein said proliferative disease or disorder is selected from the group consisting of a teratoma, an undifferentiated cancer, a leukemia, a brain cancer, a breast cancer, a colon cancer, an ovarian cancer, a pancreatic cancer, a prostate cancer, a melanoma, a liver cancer, a lung cancer, a head and neck cancer, a mesenchymal cancer and a multiple myeloma. 
     
     
         14 . The method of  claim 12 , wherein said compound is of Formula I. 
     
     
         15 . The method of  claim 14 , wherein:
 R 1  is hydrogen, and   R 2  is selected from the group consisting of:
 2,4-dioxo-5-fluoropyrimidin-1-ylcarbonyl, 
 2-methylbenzofuran-3-ylmethyleneamino, and 
 —NH—R 5 , wherein R 5  is selected from the group consisting of:
 pyridinylcarbonyl, 
 2-hydroxyl-2-phenyl-2-thiophen-2-yl-acetyl, 
 (C 1-6 )alkyl-carbonyl, 
 N-(ethoxycarbonylmethyl)-2,4-dioxo-pyrrolidine-3-ylidene-methyl, 
 naphthylsulfonyl, and 
 N-hydroxy-acetimidoyl; 
 
   or wherein:   R 1  is benzoyl and R 2  is 4-chlorobenzamido; and   R 3  and R 1  are independently selected from the group consisting of hydrogen, chloro, NH 2 , and methyl.   
     
     
         16 . The method of  claim 12 , wherein said compound is of formula II: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 12 , wherein said compound is of formula III: 
       
         
           
           
               
               
           
         
       
     
     
         18 . The method of  claim 12 , wherein said compound is of formula IV: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The method of  claim 12 , wherein said compound is of formula V: 
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 12 , wherein said compound is of formula VI:

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