Arylfluorosulfate compounds and methods

Abstract

Arylfluorosulfate compounds derived from anticancer drugs are disclosed herein, which exhibit improved anti-cancer cell proliferation activities compared to their phenolic drug precursors. Among these compounds, the fluorosulfate derivative of fulvestrant showed significantly enhanced activity to down-regulate estrogen receptor (ER) expression in ER + breast cancer cell line MCF-7, and oral availability in vivo; the fluorosulfate derivative of combretastatin A4 exhibited a 70-fold increase in potency in the drug resistant colon cancer cell line HT-29; and the fluorosulfate derivative of ABT-751 showed enhanced activity relative to ABT-751.

What is claimed is: 
     
         1 . A chemical compound comprising a fluorosulfate derivative of a phenolic anticancer medicinal agent, wherein at least one phenolic OH group of the medicinal agent is replaced by —OSO 2 F. 
     
     
         2 . The compound of  claim 1 , wherein the medicinal agent is selected from the group consisting of ATB-751 (1), apigenin (2), ezetimibe (3), topotecan (4), ganetespib (5), etoposide (6), G100713 (7), estrone (8), PI-103 (9), raloxifene (10), fulvestrant (11), mycophenolic acid (12), gimeracil (13), flavopiridol (14), serotonin (15), PAC-1 (16), SKI II (17), endoxifen (18), vanillin (19), A-769662 (20), xanthohumol (21), sirtinol (22), IOX1 (23), TWS119 (24), combretastatin A4 (25), VER-50589 (26), luminespib (27), TW-37 (28), estrol (29), SB415286 (30), rotigotine (31), estradiol (32), RKI-1447 (33), licochalcone A (34), onalespib (35), 2-methoxyestrodiol (36), SB202190 (37), salidroside (38), 10-hydroxycamptothecin (39, 10-HCPT), lasofoxifene, lipid encapsulated 7-ethyl-10-hydroxycamptothecin, (LE-SN38), diethylstilbestrol, amrubicin, genistein, and phenoxodiol. 
     
     
         3 . The compound of  claim 1 , wherein the compound has a formula selected from the group consisting of Formula 1F, Formula 11F, and Formula 25F: 
       
         
           
           
               
               
           
         
       
     
     
         4 . A pharmaceutical composition comprising the compound of  claim 1  in a pharmaceutically acceptable carrier. 
     
     
         5 . A pharmaceutical composition comprising the compound of  claim 2  in a pharmaceutically acceptable carrier. 
     
     
         6 . A pharmaceutical composition comprising the compound of  claim 3  in a pharmaceutically acceptable carrier. 
     
     
         7 . A method of treatment of cancer in a patient, comprising administering an effective dose of the compound of  claim 1  to the patient. 
     
     
         8 . A method of treatment of cancer in a patient, comprising administering an effective dose of the compound of  claim 2  to the patient. 
     
     
         9 . A method of treatment of cancer in a patient, comprising administering an effective dose of the compound of  claim 3  to the patient. 
     
     
         10 . The method of  claim 7 , wherein the patient is a human. 
     
     
         11 . The method of  claim 8 , wherein the patient is a human. 
     
     
         12 . The method of  claim 9 , wherein the patient is a human. 
     
     
         13 . The method of  claim 9  wherein the compound is a compound of Formula 1F. 
     
     
         14 . The method of  claim 9 , wherein the compound is a compound of Formula 11F. 
     
     
         15 . The method of  claim 14 , wherein the cancer is hormone receptor positive metastatic breast cancer. 
     
     
         16 . The method of  claim 9 , wherein the compound is a compound of Formula 25F.