Amino-derivatives of the sesquiterpene lactone class of natural products as prodrugs

作者：Woods James R; Mo Huaping; Bieberich Andrew A; Alavanja Tanja; Colby David A^*

来源：Medchemcomm, 2013, 4(1): 27-33.

DOI：10.1039/c2md20172k

The sesquiterpene lactone class of natural products displays a diverse array of biological activities due to the presence of the alpha-methylene-gamma-lactone motif. However, clinical translation of this class has been hampered by poor aqueous solubility and non-selective binding as a Michael acceptor at undesired targets. A prodrug approach has been developed to overcome these problems in which an amine is added into the alpha-methylene-gamma-lactone to mask this group from nucleophiles and increase solubility. The medicinal chemistry of amino-derivatives of the sesquiterpene lactones is described, beginning with synthetic development, moving into pharmacological applications, and finishing with clinical translation.

• 出版日期2013-1