Design, synthesis and biochemical studies of new 7 alpha-allylandrostanes as aromatase inhibitors

作者：Varela Carla L; Amaral Cristina; Correia da Silva Georgina; Carvalho Rui A; Teixeira Natercia A; Costa Saul C; Roleira Fernanda M F^*; Tavares da Silva Elisiario J

来源：Steroids, 2013, 78(7): 662-669.

DOI：10.1016/j.steroids.2013.02.016

• Breast cancer
• Synthetic steroids
• 7 alpha-Allylandrostanes
• Aromatase inhibitors
• Structure-activity relationships

Two series of derivatives of 7 alpha-allylandrostenedione, namely its 3-deoxo and 1-ene analogs, were designed and synthesised and their biochemical activity towards aromatase evaluated. In each of these series, the C-17 carbonyl group was further replaced by the hydroxyl and acetoxyl groups. The attained data pointed out that the absence of the C-3 carbonyl group led to a slightly decrease in the inhibitory activity and the introduction of an additional double bond in C-1 revealed to be a very beneficial structural change in the studied compounds (compound 12, IC50 = 0.47 mu M, K-i = 45.00 nM). Furthermore, the relevance of the C-17 carbonyl group in the D-ring as a structural feature required to achieve maximum aromatase inhibitory activity is also observed for this set of derivatives.

• 出版日期2013-7