Anticancer P21-activated kinase inhibitors
Compounds according to formula I: wherein Ar is a fused aryl group, R 1 is selected from alkyl and aryl amides, CF 3 , and CH 2 OH, and R 2 is selected from hydrogen, —C(═O)CH 2 NH 2 , and —C(═O)CH 2 CH 2 NH 2 are described. The compounds are effective for inhibiting p21-activated kinases, and can be used for prevention and treatment of cancer.
1. A compound according to formula I:
wherein Ar is 3-phenanthrene, R 1 is selected from —C(═O)NH-isopropyl and CF 3 and R 2 is selected from —C(═O)CH 2 NH 2 and —C(═O)CH 2 CH 2 NH 2 , and pharmaceutically acceptable salts thereof.
2. A method of treating PAK-dependent cancer by administering to a subject a therapeutically effective amount of a compound according to formula I:
wherein Ar is 3-phenanthrene, R 1 is selected from —C(═O)NH-isopropyl and CF 3 and R 2 is selected from —C(═O)CH 2 NH 2 and —C(═O)CH 2 CH 2 NH 2 , and pharmaceutically acceptable salts thereof.
3. The method of claim 2 , wherein the cancer is breast cancer.
4. The method of claim 2 , wherein the cancer is thyroid cancer.
5. A method of inhibiting one or more p21-activated kinases in a subject by administering an effective amount of a compound according to formula I:
wherein Ar is 3-phenanthrene, R 1 is selected from —C(═O)NH-isopropyl and CF 3 and R 2 is selected from —C(═O)CH 2 NH 2 and —C(═O)CH 2 CH 2 NH 2 , and pharmaceutically acceptable salts thereof.
6. The method of claim 5 , wherein a plurality of p21-activated kinases are inhibited.
7. The method of claim 5 , wherein the p21-activated kinases comprise PAK1.
8. The method of claim 5 , wherein the compound does not substantially inhibit phosphoinositide-dependent kinase-1.
9. The compound of claim 1 , wherein the compound has the structure
10. The compound of claim 1 , wherein the compound has the structure