Modulators of HEC1 activity and methods therefor
Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.
1. A antineoplastic compound having a structure according to Formula I
R 1 is OR a , SR a , or —S(O) 2 R a ;
R a is alkyl, aryl, or aryl substituted with alkyl, fluoroalkyl, halogen, or alkoxy;
R 2 and R 3 are independently alkyl or halogen, and R 4 is hydrogen; and
R 5 is optionally substituted pyridyl;
wherein each of R 1 , R 2 , R 3 , R 5 , and R a is independently optionally substituted with alkyl, fluoroalkyl, halogen, or alkoxy.
2. The compound of claim 1 wherein R 1 is SR a , OR a , or , —S(O) 2 R a , and wherein R a is aryl substituted with alkyl, fluoroalkyl, halogen, or alkoxy.
3. The compound of claim 2 wherein R 1 is SR a or OR a , and wherein R a is aryl or aryl substituted with alkoxy.
4. The compound of claim 1 having a structure selected from the group consisting of
5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 1 in a concentration effective to disrupt Hec1/Nek2binding in a patient when the composition is administered to the patient.
6. The pharmaceutical composition of claim 5 wherein the compound is a compound according to claim 4 .
7. The compound of claim 1 having the structure
8. The compound of claim 1 having the structure
9. The compound of claim 1 having the structure
10. The compound of claim 1 having the structure
11. The compound of claim 1 having the structure
12. The compound of claim 1 having the structure
13. The compound of claim 1 having the structure
14. The compound of claim 1 having the structure
15. The compound of claim 1 having the structure