Cathepsin D is a lysosomal aspartic protease found in all mammalian cells and is considered to be one of the main catabolic proteinases. Cathepsin D has been suggested to play a role in the metastatic potential of several types of cancer. 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 colon cancer, prostate cancer, uterine cancer, and ovarian cancer. Hydroxyethyl isosteres with cyclic tertiary amine have proven to be clinically useful as inhibitors of aspartyl proteases similar to cathepsin D inactivity, such as the HIV-1 aspartyl protease. We have undertaken the design, via computer molecular modeling, and the synthesis of (hydroxyethyl) amine isostere inhibitors, which are similar to potent inhibitors of the aspartyl HIV-1 protease. We now report the preparation of six compounds that contain novel hydroxyethyl isosteres with cyclic tertiary amines.
McConnell, Rose M.; Godwin, Walter E.; Stefan, Amy; Newton, Crystal; Herring, Nikki; and Goss, Crissy
"Preparation of Novel Hydroxyethyl Amine Isosteres as Potential Cathepsin D Inhibitors,"
Journal of the Arkansas Academy of Science: Vol. 56
, Article 18.
Available at: http://scholarworks.uark.edu/jaas/vol56/iss1/18