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Published on: August 13, 2019
6beta,19-Bridged androstenedione analogs as aromatase inhibitors
Sachiko Komatsu1, Ayaka Yaguchi, Kouwa Yamashita
1Tohoku Pharmaceutical University, 4-1 Komatsushima-4-chome, Aoba-ku, Sendai 981-8558, Japan.
Abstract:
Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. New 6beta,19-bridged steroid analogs of androstenedione, 6beta,19-epithio- and 6beta,19-methano compounds 11 and 17, were synthesized starting from 19-hydroxyandrostenedione (6) and 19-formylandrost-5-ene-3beta,17beta-yl diacetate (12), respectively, as aromatase inhibitors. All of the compounds including known steroids 6beta,19-epoxyandrostenedione (4) and 6beta,19-cycloandrostenedione (5) tested were weak to poor competitive inhibitors of aromatase and, among them, 6beta,19-epoxy steroid 4 provided only moderate inhibition (K(i): 2.2 microM). These results show that the 6beta,19-bridged groups of the inhibitors interfere with binding in active site of aromatase.
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