US2002115700A1PendingUtilityA1
Substituted indole compounds and methods of their use
Priority: Jul 1, 1999Filed: Feb 13, 2002Published: Aug 22, 2002
Est. expiryJul 1, 2019(expired)· nominal 20-yr term from priority
C07D 513/04A61K 31/426C07D 277/36C07D 277/34C07D 417/10A61K 31/4439C07D 417/06A61K 31/506
46
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Claims
Abstract
5-(3-Isatinylidinyl)thiazolidineones and 3-(thiazolidinon-5-yl)indoles compounds, compositions, and methods of inhibiting telomerase activity in vitro and treatment of telomerase mediated conditions or diseases ex vivo and in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of conditions or diseases mediated by telomerase activity, such as in the treatment of cancer. Also disclosed are novel methods for assaying or screening for inhibitors of telomerase activity.
Claims
exact text as granted — not AI-modifiedwe claim:
1 . A compound of formula (I):
wherein
X 1 is chosen from O, S, CH 2 , or NR 5 where R 5 is H, lower alkyl or aryl;
L 1 is a direct single bond, direct double bond, —CH 2 —, or —CH═;
is a single or a double bond;
R 1 is selected from the group consisting of H, OR 5 , SR 5 , CR 6 R 7 R 8 , and oxo only when is a single, wherein R 6 , R 7 , and R 8 are independently selected from H, OH, lower alkyl, aryl, or heteroaryl;
R 2 and R 3 are independently selected from the group consisting of H, OH, halogen, mercapto, nitro, cyano, trifluromethyl, lower alkyl, lower alkoxy, aryloxy, NR 9 R 10 , SO 2 NR 9 R 10 , OCHR 9 R 10 , COR 9 , CO 2 R 9 , NHCONHR 9 , CONHR 9 , NHCOR 9 , aryl, and heteroaryl wherein R 9 and R 10 are independently selected from the group consisting of hydrogen, lower alkyl, aryl, and heteroaryl, and R 2 and R 3 further represent replacement in the ring of ring methine (—CH═) atoms with aza (—N═) atoms;
L 2 is a direct single bond or a linking group having from 1 to 3 atoms independently selected from unsubstituted or substituted carbon, N, O or S; and
R 4 is H, lower alkyl, alkaryl, aryl, or heteroaryl;
or a pharmaceutically acceptable salt thereof.
2 . A compound of claim 1 , wherein is a double bond, and L 1 is a direct single bond, —CH 2 —, or —CH═.
3 . A compound of claim 1 , wherein is a single bond, and R 1 is H or oxo.
4 . A compound of claim 3 , wherein L 1 is a direct double bond.
5 . A compound of claim 1 , wherein R 2 and R 3 are halogen.
6 . A compound of claim 5 , wherein the halogen is Cl.
7 . A compound of claim 1 , wherein R 3 is hydrogen.
8 . A compound of claim 7 , wherein R 2 is halogen.
9 . A compound of claim 8 , wherein the halogen is Cl.
10 . A compound of claim 8 , wherein R 2 is 4-Cl, 5-Cl, or 6-Cl.
11 . A compound of claim 10 , wherein R 2 is 4-Cl.
12 . A compound of claim 7 , wherein R 2 is SO 2 NHR 9 .
13 . A compound of claim 12 , wherein R 9 is aryl.
14 . A compound of claim 12 , wherein R 9 is alkyl.
15 . A compound of claim 7 , wherein R 2 is COR 9 .
16 . A compound of claim 15 , wherein R 9 is aryl.
17 . A compound of claim 1 , wherein L 2 is a direct bond.
18 . A compound of claim 1 , wherein L 2 is selected from the group consisting of —O—, —S—, —SO—, —SO 2 —, —NH—, —(CH 2 ) n —, —(OCH 2 ) n —, —(CH 2 ) n O(CH 2 ) m —, —SCH 2 —, —OC(O)—, —C(O)NH—, —OC(O)CH 2 —, —OC(O)NH—, —NHC(O)—, and —NHC(O)NH—, where n and m are independently selected from an integer between 0 and 1.
19 . A compound of claim 18 , wherein L 2 is —CH 2 —.
20 . A compound of claim 18 , wherein L 2 is —SO2—.
21 . A compound of formula (II):
wherein
X 1 is O or S;
R 2 is H, OH, halogen, lower alkyl, aryl, or heteroaryl;
L 2 is a direct bond, CH 2 , or SO 2 ; and
R 11 is H, halogen or lower alkoxy;
or a pharmaceutically acceptable salt thereof.
22 . A compound of claim 21 , wherein X 1 is O, L 2 is CH 2 , and R 2 and R 11 are chloro.
23 . A compound of claim 1 , further having telomerase inhibiting activity.
24 . A compound of claim 21 , further having telomerase inhibiting activity.
25 . A method of inhibiting a telomerase enzyme comprising contacting the enzyme with a compound of claim 1 .
26 . A method of inhibiting a telomerase enzyme comprising contacting the enzyme with a compound of claim 21 .
27 . A method of inhibiting proliferation of a telomerase positive cell comprising contacting the cell with a compound of claim 1 .
28 . The method of claim 27 , wherein the cell is a mammalian cell.
29 . The method of claim 28 , wherein the cell is a human cell.
30 . The method of claim 29 , wherein the cell is a cancer cell.
31 . A method of treating a tumor comprising contacting the tumor with a compound of claim 1 .
32 . A method of treating a tumor comprising contacting the tumor with a compound of claim 21 .
33 . A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
34 . A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 21 and a pharmaceutically acceptable carrier.
35 . The use of a compound of claim 1 to inhibit telomerase activity.
36 . The use of a compound of claim 21 to inhibit telomerase activity.
37 . The use of a compound of claim 1 to inhibit proliferation of a telomerase positive cell.
38 . The use of a compound of claim 21 to inhibit proliferation of a telomerase positive cell.
39 . The use of a compound of claim 1 in the manufacture of a medicament for inhibition of telomerase activity.
40 . The use of a compound of claim 21 in the manufacture of a medicament for inhibition of telomerase activity.
41 . The use of a compound of claim 1 in the manufacture of a medicament for inhibition of telomerase activity in a cell.
42 . The use of a compound of claim 21 in the manufacture of a medicament for inhibition of telomerase activity in a cell.
43 . The use of a compound of claim 1 in the manufacture of a medicament for the treatment of a telomerase mediated condition or disease.
44 . The use of a compound of claim 21 in the manufacture of a medicament for the treatment of a telomerase mediated condition or disease.Join the waitlist — get patent alerts
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