Compounds, compositions, and methods for preventing metasasis of cancer cells

Abstract

Disclosed are methods for preventing metastasis of cancer cells. The disclosed compounds can be used to prevent the spread of tumor or other types of cancer cells.

1 - 20 . (canceled) 
     
     
         21 . A method for treating an ocular condition comprising administering to a subject in need thereof:
 a) a therapeutically-effective amount of a compound; and   b) a therapeutically-effective amount of an anti-VEGF agent,   
       wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
       wherein R is a substituted or unsubstituted thiazolyl unit having the formula: 
       
         
           
           
               
               
           
         
       
       R 2 , R 3 , and R 4  are each independently:
 i) hydrogen; 
 ii) substituted or unsubstituted C 1 -C 6  linear, C 3 -C 6  branched, or C 3 -C 6  cyclic alkyl; 
 iii) substituted or unsubstituted C 2 -C 6  linear, C 3 -C 6  branched, or C 3 -C 6  cyclic alkenyl; 
 iv) substituted or unsubstituted C 2 -C 6  linear or C 3 -C 6  branched alkynyl; 
 v) substituted or unsubstituted C 6  or C 10  aryl; 
 vi) substituted or unsubstituted C 1 -C 9  heteroaryl; 
 vii) substituted or unsubstituted C 1 -C 9  heterocyclic; or 
 viii) R 2  and R 3  taken together form a saturated or unsaturated ring having from 5 to 7 atoms; wherein from 1 to 3 atoms can optionally be oxygen, nitrogen, or sulfur; 
 
       Z is a unit having the formula:
   -(L) n -R 1    
 
       R 1  is:
 i) hydrogen; 
 ii) hydroxyl; 
 iii) amino; 
 iv) substituted or unsubstituted C 1 -C 6  linear, C 3 -C 6  branched, or C 3 -C 6  cyclic alkyl; 
 vi) substituted or unsubstituted C 1 -C 6  linear, C 3 -C 6  branched, or C 3 -C 6  cyclic alkoxy; 
 vi) substituted or unsubstituted C 6  or C 10  aryl; 
 vii) substituted or unsubstituted C 1 -C 9  heterocyclic rings; or 
 viii) substituted or unsubstituted C 1 -C 9  heteroaryl rings; 
 
       L is a linking unit having the formula:
   -[Q] y [C(R 5a R 5b )] x [Q 1 ] z [C(R 6a R 6b )] w —
 
 
       Q and Q 1  are each independently:
 i) —C(O)—; 
 ii) —NH—; 
 iii) —C(O)NH—; 
 iv) —NHC(O)—; 
 v) —NHC(O)NH—; 
 vi) —NHC(O)O—; 
 vii) —C(O)O—; 
 viii) —C(O)NHC(O)—; 
 ix) —O—; 
 x) —S—; 
 xi) —SO 2 —; 
 xii) —C(═NH)—; 
 xiii) —C(═NH)NH—; 
 xiv) —NHC(═NH)—; or 
 xv) —NHC(═NH)NH—; 
 
       R 5a  and R 5b  are each independently:
 i) hydrogen; 
 ii) hydroxy; 
 iii) halogen; 
 iv) substituted or unsubstituted C 1 -C 6  linear or C 3 -C 6  branched alkyl; or 
 v) a unit having the formula:
   —[C(R 7a R 7b )] t R 8  
 
 
 
       R 7a  and R 7b  are each independently:
 i) hydrogen; or 
 ii) substituted or unsubstituted C 1 -C 6  linear, C 3 -C 6  branched, or C 3 -C 6  cyclic alkyl; 
 
       R 8  is:
 i) hydrogen; 
 ii) substituted or unsubstituted C 1 -C 6  linear, C 3 -C 6  branched, or C 3 -C 6  cyclic alkyl; 
 iii) substituted or unsubstituted C 6  or C 10  aryl; 
 iv) substituted or unsubstituted C 1 -C 9  heteroaryl; or 
 v) substituted or unsubstituted C 1 -C 9  heterocyclic; 
 
       R 6a  and R 6b  are each independently:
 i) hydrogen; or 
 ii) C 1 -C 4  linear or C 3 -C 4  branched alkyl; 
 
       the index n is 0 or 1; the indices t, w and x are each independently from 0 to 4; the indices y and z are each independently 0 or 1; or 
       a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 21 , wherein R has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         23 . The method of  claim 22 , wherein R 4  is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, or tert-butyl. 
     
     
         24 . The method of  claim 22 , wherein R 4  is phenyl, thiophen-2-yl, or thiophen-3-yl. 
     
     
         25 . The method of  claim 22 , wherein R 4  is thiophen-2-yl. 
     
     
         26 . The method of  claim 21 , wherein R 1  is methoxy. 
     
     
         27 . The method of  claim 21 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         28 . The method of  claim 21 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         29 . The method of  claim 21 , wherein R has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         30 . The method of  claim 29 , wherein R 2  and R 3  are independently hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, or tert-butyl. 
     
     
         31 . The method of  claim 29 , wherein R 2  is ethyl. 
     
     
         32 . The method of  claim 29 , wherein R 2  is phenyl, thiophen-2-yl, or thiophen-3-yl. 
     
     
         33 . The method of  claim 29 , wherein R 2  is thiophen-2-yl. 
     
     
         34 . The method of  claim 21 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         35 . The method of  claim 21 , wherein the compound is in the form of a salt of ammonium, sodium, lithium, potassium, calcium, magnesium, bismuth, or lysine. 
     
     
         36 . The method of  claim 21 , wherein the anti-VEGF agent inhibits angiogenesis. 
     
     
         37 . The method of  claim 21 , wherein the ocular condition is eye cancer. 
     
     
         38 . The method of  claim 21 , wherein the ocular condition is intraocular melanoma. 
     
     
         39 . The method of  claim 21 , wherein the ocular condition is retinoblastoma. 
     
     
         40 . The method of  claim 21 , wherein the compound is administered subcutaneously.