876617-33-3Relevant academic research and scientific papers
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.
SUBSTITUTED BENZOTHIOPHENE ANALOGS AS SELECTIVE ESTROGEN RECEPTOR DEGRADERS
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Paragraph 0312; 0315; 0339; 0340; 0345; 0346; 0399; 0400, (2019/08/29)
In one aspect, the disclosure relates to relates to substituted benzothiophene analogs which are useful as selective degraders of estrogen receptor, methods of making same, pharmaceutical compositions comprising same, and methods of treating one or more clinical conditions associated with estrogen receptor, such as a cancer, including breast cancer, or osteoporosis. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
DERIVATIVES OF 2,3-DIPHENYLCHROMENE USEFUL FOR THE TREATMENT OF CANCER
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Page/Page column 155, (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.
OXAZOLE DERIVATIVES AS HISTAMINE H3 RECEPTOR AGENTS, PREPARATION AND THERAPEUTIC USES
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Page/Page column 65, (2008/06/13)
The present invention discloses novel aryl oxazole compounds of Formula I (I), or pharmaceutically acceptable salts thereof, which have histamine-H3 receptor antagonist or inverse agonist activity, as well as methods for preparing and using such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using these compositions to treat obesity, cognitive deficiencies, narcolepsy, and other histamine H3 receptor-related diseases. Formula I (I) or a pharmaceutically acceptable salt thereof, wherein: m is independenlly at each occurrence 1, 2, or 3, Z independently represents carbon (substituted with hydrogen or the optional substituents indicated herein) or nitrogen, provided that when Z is nitrogen then R6 is not attached to Z; R1 and R2 are independently -(C1-C7) alkyl(optionally substituted with one to three halogens), or R1 and R2 and the nitrogen to which they are attached form an azetidinyl ring, a pyrrolidinyl ring, or a piperidinyl ring, wherein further the azetidinyl, pyrrolidinyl, or piperidinyl ring so formed may be optionally substituted one to three times with R5; R6 is independently at each occurrence -H, -halogen, or -CH3.
