An efficient approach to novel 17-5 %26apos;-(1 %26apos;,2 %26apos;,4 %26apos;)-oxadiazolyl androstenes via the cyclodehydration of cytotoxic O-steroidacylamidoximes, and an evaluation of their inhibitory action on 17 alpha-hydroxylase/C-17,C-20-lyase

作者：Kovacs Dora; Woelfling Janos; Szabo Nikoletta; Szecsi Mihaly; Kovacs Ida; Zupko Istvan; Frank Eva^*

来源：European Journal of Medicinal Chemistry, 2013, 70: 649-660.

DOI：10.1016/j.ejmech.2013.10.038

• Steroids
• O-Acylamidoximes
• Antiproliferative activity
• 1,2,4-Oxadiazoles
• P450(17 alpha) inhibitor

Novel 17-exo-oxadiazoles in the androst-5-ene series were efficiently synthesized in a two-step sequence via the corresponding O-acylamidoxime intermediates (obtained from steroidal 17-carboxylic acids and amidoximes in the presence of coupling reagent), which then underwent tetrabutylammonium fluoride-induced cyclocondensation under mild reaction conditions. The synthesized compounds were subjected to in vitro pharmacological studies to investigate their inhibitory effect on rat testicular C-17,C-20-lyase and their antiproliferative action on four malignant human adherent cell lines (HeLa, MCF7, A2780 and A431). One of the oxadiazolyl derivatives proved to exert significant enzyme-inhibitory action (IC50 = 0.60 mu M), while some of the isolated O-acylated amidoxime intermediates displayed high cytotoxic activities on all examined cell lines, with IC50 values in the range 0.22-3.94 mu M.

• 出版日期2013-12