AGENTS FOR DIFFERENTIATING STEM CELLS AND TREATING CANCER
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.