Peptide mimetic ligands of polo-like kinase 1 polo box domain and methods of use

摘要

Found in various eukaryotic organisms, polo-like kinases (collectively, Plks) are a conserved subfamily of Ser/Thr protein kinases that play critical roles in cell proliferation. Provided herein are compounds that specifically inhibit the activity of Plks, specifically Plk1. Further provided herein are methods for use of the compounds for the treatment of hyperproliferative disorders, particularly cancer. Also provided are uses of the compounds for the preparation of a medicament.

主权项

1. A compound comprising the structure:wherein
Z is selected from the group consisting of: O, CH2, and CF2; R1X is selected from the group consisting of: R1—CH═N—O—; R1—CH2—CH2—O—; R1—C(O)—NH—O—; R1—CH2—CH2—CH2—; and R1—CH2—CH2—S—; R1 is selected from the group consisting of: Y is a group selected from the group consisting of: aryl, heteroaryl, lower alkyl, higher alkyl, lower alkene, higher alkene, halogen, amine, amide, carboxyl, olefin, and carbonyl; or any pharmaceutically acceptable salt thereof.