Journal of Medicinal Chemistry p. 3636 - 3657 (2019)
Update date:2022-08-16
Topics:
Roleira, Fernanda M. F.
Varela, Carla
Amaral, Cristina
Costa, Saul C.
Correia-Da-Silva, Georgina
Moraca, Federica
Costa, Giosuè
Alcaro, Stefano
Teixeira, Natércia A. A.
Tavares Da Silva, Elisiário J.
C-6α and C-7α androstanes were studied to disclose which position among them is more convenient to functionalize to reach superior aromatase inhibition. In the first series, the study of C-6 versus C-7 methyl derivatives led to the very active compound 9 with IC50 of 0.06 μM and Ki = 0.025 μM (competitive inhibition). In the second series, the study of C-6 versus C-7 allyl derivatives led to the best aromatase inhibitor 13 of this work with IC50 of 0.055 μM and Ki = 0.0225 μM (irreversible inhibition). Beyond these findings, it was concluded that position C-6α is better to functionalize than C-7α, except when there is a C-4 substituent simultaneously. In addition, the methyl group was the best substituent, followed by the allyl group and next by the hydroxyl group. To rationalize the structure-activity relationship of the best inhibitor 13, molecular modeling studies were carried out.
View MoreWeifang Adde Economic And Trade Co.,LTD.
Contact:86-536-8885548
Address:Room 1402,Wanda Plaza B Block,No.958,Yuanfei Road,Kuiwen District
Contact:+86 21 34123252
Address:14, 4580 Dushi, Shanghai, China
Shandong Xinhua Pharmaceutical Co.,Ltd
website:http://www.xhzy.com
Contact:+86-533-2196801
Address:1 lutai road,zhangdian dis,Zibo City
Hangzhou Bayee Chemical Co.,Ltd.
Contact:+86-571-86990109
Address:No.380, Jiangnan Auenue, Binjiang District, Hangzhou, China
Contact:13357117572
Address:No.149 Shiji dadao Road.
Doi:10.1016/S0040-4039(01)82041-4
(1981)Doi:10.1002/anie.201705753
(2017)Doi:10.3390/12040861
(2007)Doi:10.1021/ja800200r
(2008)Doi:10.1002/aoc.5935
(2020)Doi:10.1021/ja00353a057
(1983)