Cathepsin D has been suggested to play important roles in the metastatic potential of several types of cancer.  Also, a high activated cathepsin D level in breast tumor tissue has been associated with an increased incidence of relapse and metastasis.  High levels of active cathepsin D have also been found in lung cancer, colon cancer, prostate cancer, uterine cancer, and ovarian cancer.  In fact cathepsin D levels have been used as markers to predict the prognosis of breast cancer and uterine cancer patients.  The design and synthesis of new (hydroxyethyl)amine isosteres containing cyclized tertiary amines as inhibitors as cathepsin D is reported.  These compounds utilize substituted piperazines as the hydroxyethyl tertiary amine. Ki values by fluorometric assay for inhibition of Cathepsin D hydrolysis of substrate: Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly-Lys(Methyl Red)-Glu-NH2 is reported.

Development of new cathepsin D inhibitors with hydroxyethylamine isosteres

239th National Meeting (2010)

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