1373116-44-9Relevant articles and documents
New structure-activity relationships of A-and D-ring modified steroidal aromatase inhibitors: Design, synthesis, and biochemical evaluation
Varela, Carla,Tavares Da Silva, Elisiário J.,Amaral, Cristina,Correia Da Silva, Georgina,Baptista, Teresa,Alcaro, Stefano,Costa, Giosuè,Carvalho, Rui A.,Teixeira, Natércia A. A.,Roleira, Fernanda M. F.
experimental part, p. 3992 - 4002 (2012/07/30)
A- and D-ring androstenedione derivatives were synthesized and tested for their abilities to inhibit aromatase. In one series, C-3 hydroxyl derivatives were studied leading to a very active compound, when the C-3 hydroxyl group assumes 3β stereochemistry (1, IC50 = 0.18 μM). In a second series, the influence of double bonds or epoxide functions in different positions along the A-ring was studied. Among epoxides, the 3,4-epoxide 15 showed the best activity (IC50 = 0.145 μM) revealing the possibility of the 3,4-oxiran oxygen resembling the C-3 carbonyl group of androstenedione. Among olefins, the 4,5-olefin 12 (IC50 = 0.135 μM) revealed the best activity, pointing out the importance of planarity in the A,B-ring junction near C-5. C-4 acetoxy and acetylsalicyloxy derivatives were also studied showing that bulky substituents in C-4 diminish the activity. In addition, IFD simulations helped to explain the recognition of the C-3 hydroxyl derivatives (1 and 2) as well as 15 within the enzyme.
