Integrin-linked kinase inhibitors
A number of compounds and use of the compounds in a method for treating or preventing cancer in a subject by administering to the subject a pharmaceutical composition including a compound of formula I or a pharmaceutically acceptable salt thereof are described. The compounds can also be used to inhibit integrin-linked kinase in a cell, which has an effect on the Akt signaling pathway.
1. A compound according to Formula I:
wherein Ar is a substituted or unsubstituted biphenyl group;
Y is selected from the group consisting of sulfonamide,
wherein n is an integer from 0-3,
R 1 is H, methyl, ethyl, propyl, i-propyl, or benzyl; and R 2 is H, methyl or ethyl; and
X is
wherein
R 4 is H, methyl, ethyl, allyl, CH 2 CH 2 OH, or CH 2 CN;
or pharmaceutically acceptable salts thereof.
2. The compound of claim 1 wherein Ar is a biphenyl group according to formula II
wherein R 5 is H, methyl, ethyl, propyl, isopropyl, tert-butyl, CF 3 , CCl 3 , hydroxyl, OMe, CN, NO 2 , NH 2 , CONH 2 , CONHMe, acetate, CO 2 H, CO 2 Me, F, Cl, Br, or I.
3. The compound of claim 2 where R 5 is CF 3 .
4. The compound of claim 3 , wherein X is piperazine, Y
and R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl.
5. The compound of claim 3 wherein X is piperazine, Y is
and R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl.
6. The compound of claim 5 , wherein R 1 is methyl or ethyl.
7. The compound of claim 3 wherein X is
Y is
and R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl.
8. The compound of claim 3 wherein X is
Y is
and R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl.
9. The compound of claim 2 wherein R 5 is CN, Y is
and R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl.
10. The compound of claim 2 wherein R 5 is methyl, Y is
and R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl.
11. The compound of claim 2 , wherein R 5 is hydrogen, Y is
and R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl.
12. A method for treating cancer in a subject, wherein the cancer is selected from the group consisting of leukemia, non-small cell lung cancer, colon cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer, comprising administering to the subject a pharmaceutical composition including a compound of formula I or a pharmaceutically acceptable salt thereof,
wherein Ar is a substituted or unsubstituted biphenyl group;
Y is selected from the group consisting of sulfonamide,
and
wherein n is an integer from 0-3, R 1 is H, methyl, ethyl, propyl, i-propyl, or benzyl; and R 2 is H, methyl or ethyl; and
X is
wherein
R 4 is methyl, ethyl, allyl, CH 2 CH 2 OH, or CH 2 CN.
13. The method of claim 12 , wherein X is piperazine, Y is
and Ar is a biphenyl group according to formula II
wherein R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl and R 5 is H, methyl, ethyl, propyl, isopropyl, tert-butyl, CF 3 , CCl 3 , hydroxyl, OMe, CN, NO 2 , NH 2 , CONH 2 , CONHMe, acetate, CO 2 H, CO 2 Me, F, Cl, Br, or I.
14. The method of claim 13 , wherein R 1 is methyl or ethyl and R 5 is CF 3 .
15. A method of inhibiting integrin-linked kinase in a cell by contacting the cell with a compound of formula I or a pharmaceutically acceptable salt thereof,
wherein Ar is a substituted or unsubstituted biphenyl group;
Y is selected from the group consisting of sulfonamide,
wherein n is an integer from 0-3,
R 1 is H, methyl, ethyl, propyl, i-propyl, or benzyl; and R 2 is H, methyl or ethyl; and
X is
wherein
R 4 is methyl, ethyl, allyl, CH 2 CH 2 OH, or CH 2 CN.
16. The method of claim 15 , wherein X is piperazine, Y is
and Ar is a biphenyl group according to formula II
wherein R 1 is H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl and R 5 is H, methyl, ethyl, propyl, isopropyl, tert-butyl, CF 3 , CCl 3 , hydroxyl, OMe, CN, NO 2 , NH 2 , CONH 2 , CONHMe, acetate, CO 2 H, CO 2 Me, F, Cl, Br, or I.
17. The method of claim 16 , wherein R 1 is methyl or ethyl and R 5 is CF 3 .