1443983-85-4Relevant articles and documents
Maximizing ER-α Degradation Maximizes Activity in a Tamoxifen-Resistant Breast Cancer Model: Identification of GDC-0927
Kahraman, Mehmet,Govek, Steven P.,Nagasawa, Johnny Y.,Lai, Andiliy,Bonnefous, Celine,Douglas, Karensa,Sensintaffar, John,Liu, Nhin,Lee, Kyoungjin,Aparicio, Anna,Kaufman, Josh,Qian, Jing,Shao, Gang,Prudente, Rene,Joseph, James D.,Darimont, Beatrice,Brigham, Daniel,Heyman, Richard,Rix, Peter J.,Hager, Jeffrey H.,Smith, Nicholas D.
supporting information, p. 50 - 55 (2019/01/15)
The further optimization of ER-α degradation efficacy of a series of ER modulators by refining side-chain substitution led to efficacious selective estrogen receptor degraders (SERDs). A fluoromethyl azetidine group was found to be preferred and resulted
Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer
Lu, Yunlong,Gutgesell, Lauren M.,Xiong, Rui,Zhao, Jiong,Li, Yangfeng,Rosales, Carlo I.,Hollas, Michael,Shen, Zhengnan,Gordon-Blake, Jesse,Dye, Katherine,Wang, Yueting,Lee, Sue,Chen, Hu,He, Donghong,Dubrovyskyii, Oleksii,Zhao, Huiping,Huang, Fei,Lasek, Amy W.,Tonetti, Debra A.,Thatcher, Gregory R. J.
, p. 11301 - 11323 (2019/12/27)
The clinical steroidal selective estrogen receptor (ER) degrader (SERD), fulvestrant, is effective in metastatic breast cancer, but limited by poor pharmacokinetics, prompting the development of orally bioavailable, nonsteroidal SERDs, currently in clinical trials. These trials address local breast cancer as well as peripheral metastases, but patients with brain metastases are generally excluded because of the lack of blood-brain barrier penetration. A novel family of benzothiophene SERDs with a basic amino side arm (B-SERDs) was synthesized. Proteasomal degradation of ERα was induced by B-SERDs that achieved the objectives of oral and brain bioavailability, while maintaining high affinity binding to ERα and both potency and efficacy comparable to fulvestrant in cell lines resistant to endocrine therapy or bearing ESR1 mutations. A novel 3-oxyazetidine side chain was designed, leading to 37d, a B-SERD that caused endocrine-resistant ER+ tumors to regress in a mouse orthotopic xenograft model.
DERIVATIVES OF 2,3-DIPHENYLCHROMENE USEFUL FOR THE TREATMENT OF CANCER
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Page/Page column 158, (2016/07/05)
Described herein are compounds that are estrogen receptor modulators of Formula I and stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.
