Agents for differentiating stem cells and treating cancer

Abstract

The present application discloses a method for identifying an agent for the treatment or prevention of cancer or metastatic cancer comprising the steps of contacting stem cell with a potential agent, and identifying an agent that induces differentiation, or inhibits stem cell pluripotency or growth of the stem cell, wherein such agent is determined to be an anti-cancer agent.

1 .- 41 . (canceled) 
     
     
         42 . A compound of Formula 8: 
       
         
           
           
               
               
           
         
         wherein,
 X is O, NH, S, or CH2; 
 Y is O, N—R1, N—CH2-R1, CH—R1, or CH—CH2-R1; 
 R0 is H, or C1-C5 alkyl 
 R1 is H, C1-5 alkyl, optionally substituted aryl, or optionally substituted heteroaryl; 
 R2 is H, or optionally substituted aryl; and 
 R3 is H or C1-3 alkyl; where m is 0 or 1; and n is 0 or 1, 
 where “substituted” means substituted with one or more independently selected from halogen, trifluoromethyl, methylcarboxy, ethylcarboxy, methoxy, ethoxy, C1-C6 alkoxy, C1-C6 alkyl, —OH, —OCH3, —OC2H5, —O—C1-C4 alkyl, —SH, —NH 2 , —N 3 , —CN, —NO 2 , —CHO, —COOH, —CONH 2 , —C(═NH)NH 2 , or —SO 3 H. 
 
       
     
     
         43 .- 48 . (canceled) 
     
     
         49 . The compound of Formula 15: 
       
         
           
           
               
               
           
         
         wherein,
 R1 is H, optionally substituted C1-C6 alkyl; optionally substituted C2-C6 alkenyl; 
 
         optionally substituted C1-C6 alkoxy; optionally substituted C6-C12 aryl; optionally substituted C1-C9 heteroaryl with 1 to 4 ring atoms independently selected from N, S, and O; optionally substituted C7-C15 arylalkyl such as but not limited to benzyl or alpha-methylbenzyl; optionally substituted C2-C15 heteroarylalkyl with 1 to 4 ring atoms independently selected from N, S, and O; optionally substituted C7-C15 arylalkenyl; optionally substituted C3-C8 cycloalkyl; or an optionally substituted C4-C8 cycloalkylalkyl;
 R2 is hydrogen, C1-C6 alkoxy such as but not limited to methoxy or ethoxy, trifluoromethyl, halogen, methylcarboxy, ethylcarboxy, optionally substituted C1-C6 alkyl, —OH, —SH, —NH 2 , —N 3 , —CN, —NO 2 , —CHO, —COOH, —CONH 2 , —C(═NH)NH 2 , or —SO 3 H; 
 R5 is H, methyl, ethyl, C1-C6 alkyl, C1-C3 arylalkyl, or 2-phenylethyl; 
 Z2 is a bond, —NH—, —O—, —S—, —CH(CH 3 )—, —CH 2 —, —(CH 2 ) n —, —CH═CH—, —CO—, —SO—, —SO 2 —, —C(═NH)—, —CH 2 NH(CO)—, —CH 2 NH(CO)O—, —CH2NH(CO)NH—; —(CH 2 ) n NH(CO)—, —(CH 2 ) n NH(CO)O—, —(CH 2 ) m NH(CO)NH—; and 
 R4 is H, optionally substituted C1-C9 alkyl such as but not limited to tert-butyl; optionally substituted C2-C6 alkenyl; optionally substituted C6-C12 aryl such as but not limited to optionally substituted phenyl; optionally substituted C1-C9 heteroaryl with 1 to 4 ring atoms independently selected from N, S, and O; optionally substituted C7-C15 arylalkyl such as but not limited to benzyl or alpha-methylbenzyl; —O-tert-butyl; where m=1-5; n=1-8; 
 where “substituted” means substituted with one or more independently selected from halogen, trifluoromethyl, methylcarboxy, ethylcarboxy, methoxy, ethoxy, C1-C6 alkoxy, C1-C6 alkyl, —OH, —SH, —NH 2 , —N 3 , —CN, —NO 2 , —CHO, —COOH, —CONH 2 , —C(═NH)NH 2 , or —SO 3 H. 
 
       
     
     
         50 .- 51 . (canceled) 
     
     
         52 . A method of treating cancer in a subject, comprising administering to the subject a compound of Formula 1 to 17, or as set forth in  FIG. 18A-18E , or a compound as drawn out in the present specification at or about pages 48-64. 
     
     
         53 . The method according to  claim 52 , wherein the compound is any as depicted as drawn out in the present specification at or about pages 48-64. 
     
     
         54 . The method according to  claim 52 , wherein the cancer is a MUC1 positive or MUC1* positive cancer. 
     
     
         55 . The method according to  claim 52 , wherein the cancer is an NME7 AB  or NME7-X1 positive cancer. 
     
     
         56 .- 67 . (canceled) 
     
     
         68 . The compound of  claim 42 , wherein X is O or XH, R0 is C1-C5 alkyl, Y is CH—R1, and R1 is optionally substituted heteroaryl; R2 and R2 are hydrogen, m and n are 1. 
     
     
         69 . The compound of  claim 68 , wherein the compound is MN1428 or MN1442. 
     
     
         70 . The compound of  claim 49 , wherein R1 is H, R2 is H, R5 is methyl, Z2 is NH, R4 is optionally substituted C1-C9 alkyl such as but not limited to tert-butyl. 
     
     
         71 . The compound of  claim 70 , wherein the compound is MN1423. 
     
     
         72 . The method of  claim 52 , wherein compound belongs to Formula 8. 
     
     
         73 . The method of  claim 72 , wherein in Formula 8, X is O or XH, R0 is C1-C5 alkyl, Y is CH—R1, and R1 is optionally substituted heteroaryl; R2 and R2 are hydrogen, m and n are 1. 
     
     
         74 . The method of  claim 73 , wherein the compound is MN1428 or MN1442. 
     
     
         75 . The method of  claim 52 , wherein the compound belongs to Formula 15. 
     
     
         76 . The method of  claim 75 , wherein in Formula 15, R1 is H, R2 is H, R5 is methyl, Z2 is NH, R4 is optionally substituted C1-C9 alkyl such as but not limited to tert-butyl. 
     
     
         77 . The method of  claim 76 , wherein the compound is MN1423.