Novel group of stat3 pathway inhibitors and cancer stem cell pathway inhibitors

Abstract

The present invention relates to the use of a novel class of cancer stem cell pathway (CSCP) inhibitors; to methods of using such compounds to treat refractory, recurrent, or metastatic cancers; to methods of selective killing cancer cells by using such compounds with specific administration regimen; to methods of targeting cancer stem cells by inhibiting Stat3 pathway; to methods of using novel compounds in the treatment of conditions or disorders in a mammal related to aberrant Stat3 pathway activity; and to processes for preparing such compounds and intermediates thereof, and to the pharmaceutical compositions of relevant compounds, and to the specific methods of administration of these compounds.

1 .- 114 . (canceled) 
     
     
         115 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         116 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         117 . A process of preparing the compound according to  claim 115 , comprising:
 a) reacting 2-acetylnaphtho[2,3-b]furan-4,9-dione and a solution selected from the group consisting of lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, and potassium bis(trimethylsilyl)amide; and   b) adding a solution of dimethyl chlorophosphate.   
     
     
         118 . The process according to  claim 117 , further comprising:
 c) adding the reaction mixture to CH 2 Cl 2 ;   d) washing the mixture of step c) with saturated aqueous ammonium chloride;   e) drying the isolated organic fractions over magnesium sulfate; and   f) purifying the mixture of step e) via column chromatography.   
     
     
         119 . A process of preparing the compound according to  claim 116 , comprising:
 reacting phosphoric acid mono-[1-(4,9-dioxo-3a,4,9,9a-tetrahydro-naphtho[2,3-b]furan-2-yl)-vinyl]ester with trimethylsilyl bromide.