Comparative Study
doi: 10.1016/j.bmcl.2007.09.073.
Epub 2007 Sep 26.
A phosphorylated prodrug for the inhibition of Pin1
Affiliations
- PMID: 17935986
- PMCID: PMC2277516
- DOI: 10.1016/j.bmcl.2007.09.073
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Comparative Study
A phosphorylated prodrug for the inhibition of Pin1
Bioorg Med Chem Lett.
.
Abstract
Fmoc-pSer-Psi[(Z)CHC]-Pro-(2)-N-(3)-ethylaminoindole 1, showed moderate inhibition towards the mitotic regulator, Pin1 (IC(50)=28.3microM). To improve the cell permeability, the charged phosphate was masked as the bis-pivaloyloxymethyl (POM) phosphate in Fmoc-(bisPOM)-pSer-Psi[(Z)CHC]-Pro-(2)-N-(3)-ethylaminoindole 2. Antiproliferative activity towards A2780 ovarian cancer cells of 1 (IC(50)=46.2microM) was improved significantly in 2 (IC(50)=26.9microM), comparable to the IC(50) of 1 towards Pin1 enzymatic activity.
Figures
Phosphorylated Pin1 inhibitors without (1) and with (2) bis- POM prodrug masking group.
Lactonization of intermediate 3.
Synthesis of inhibitor 1.
Synthesis of prodrug 2.
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