The estrogen receptor is a target for therapeutic agents for hormone replacement in menopausal women,osteoporosis, reproductive cancers such as breast cancer,uterine cancer and prostate cancer.1,4-Dihydrothieno[3＇,2＇：5,6]thiopyrano[4,3- c]pyrazole-3-carboxylic amide derivatives were designed,synthesized and biological evaluated as potential estrogen receptor antagonists.
Rui SunJing SongSi Jie LiuHui ZhaoChun Li YanAi Jun ZhangDiwa KoiralaDa Wei LiChun Hu
A new series of 4,5-dihydro-lH-thiochromeno[4,3-d]pyrimidine derivatives have been designed and synthesized. The anti- tumor activities of the target compounds have been evaluated in vitro against two human cancer cell lines including A549 （human alveolar adenocarcinoma cell） and H460 （human lung cancer） by MTT assay. Most of the target compounds exhibited significant antitumor activities against A549 and H460 cancer cell lines. The most potent compound 4-（benzo[d][1,3]dioxol- 5-yl）-8,9-difluoro-2-（4-methylpiperazin-l-yl）-4,5-dihydro-1H-thiochromeno[4,3-d]pyrimidine （CH05） （IC50 = 0.44 μM, 3.07 μM） was 2.0 and 8.4 times more active than gefitinib （IC50= 0.89 μM, 16.81 μM） against A549 and H460 cell lines, respectively.
Based on the principles of the bioisosterism, combination of the active substructures of selective estrogen receptor modulators which are currently therapeutic agents available for the prevention and treatment of various estrogen dependent diseases, and structural optimization, a novel series of 2-aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]- chromen derivatives was designed as potent selective estrogen receptor modulators via molecular docking. The target compounds have been synthesized, and characterized by 1R, proton NMR, ESI-MS, elemental analysis and evaluated for their antitumor activity against human osteosarcoma U2OS-EGFP-4FI2G cell line. Some target compounds showed good inhibition effects on U2OS-EGFP-4F12G cell line and the preliminary structure-activity relationships were discussed.
WANG Shi-huiWANG YanZHU Yu-yingLIU Si-jieHAN JianZHOU Yi-fanLI Da-weiKOIRALA DiwaHU Chun
Five 1,4-dihydrothieno[3＇,2＇：5,6]thiopyrano[4,3-c]pyrazole-3-carboxylic amide derivatives were synthesized from 2- mercaptothiophene via a six-step procedure. The prepared compounds were initially evaluated for their antiprolifemtive activity using the estrogen receptors expressing MCF-7 human mammary tumor cell line in vitro. All of the prepared compounds showed moderate anti-tumor activity.
