206434-77-7Relevant academic research and scientific papers
Benzothiophene derivatives as selective estrogen receptor covalent antagonists: Design, synthesis and anti-ERα activities
Bai, Chengfeng,Luo, Guoshun,Ren, Shengnan,Wu, Shuangjie,Xiang, Hua,Zhu, Meiqi
, (2021/09/13)
Estrogen receptor α emerged as a well validated therapeutic target of breast cancer for decades. However, approximately 50% of patients who initially responding to standard-of-care (SoC), such as undergo therapy of Tamoxifen, generally inevitably progress to an endocrine-resistance ER+ phenotype. Recently, selective estrogen receptor covalent antagonists (SERCAs) targeted to ERα have been demonstrated as a therapeutic alternative. In the present study, series of novel 6-OH-benzothiophene (BT) derivatives targeting ERα and deriving from Raloxifene were designed, synthesized, and biologically evaluated as covalent antagonists. Driven by the antiproliferative efficacy in ER+ breast cancer cells, our chemical optimization finally led to compound 19d that with potent antagonistic activity in ER+ tumor cells while without agonistic activity in endometrial cells. Moreover, the docking simulation was carried out to elucidate the binding mode, revealing 19d as an antagonist and covalently binding to the cysteine residue at the 530 position of ER helix H11.
ANTI-CANCER NUCLEAR HORMONE RECEPTOR-TARGETING COMPOUNDS
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Page/Page column 248; 250, (2019/12/04)
The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation.
A Nickel-Catalyzed Carbonyl-Heck Reaction
Vandavasi, Jaya Kishore,Hua, XiYe,Halima, Hamdi Ben,Newman, Stephen G.
supporting information, p. 15441 - 15445 (2017/11/10)
The use of transition-metal catalysis to enable the coupling of readily available organic molecules has greatly enhanced the ability of chemists to access complex chemical structures. In this work, an intermolecular coupling reaction that unites organotriflates and aldehydes is presented. A unique catalyst system is identified to enable this reaction, featuring a Ni0 precatalyst, a tridentate Triphos ligand, and a bulky amine base. This transformation provides access to a variety of ketone-containing products without the selectivity- and reactivity-related challenges associated with more traditional Friedel–Crafts reactions. A Heck-type mechanism is postulated, wherein the π bond of the aldehyde takes the role of the olefin in the insertion/elimination steps.
BENZOTHIOPHENE DERIVATIVES AS ESTROGEN RECEPTOR INHIBITORS
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Page/Page column 60-61, (2015/01/16)
A compound of formula (I), or a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.
Benzothiophenes containing a piperazine side chain as selective ligands for the estrogen receptor α and their bioactivities in vivo
Yang, Chunhao,Xu, Guangyu,Li, Jia,Wu, Xihan,Liu, Bo,Yan, Xueming,Wang, Mingwei,Xie, Yuyuan
, p. 1505 - 1507 (2007/10/03)
The synthesis of benzothiophenes containing a piperazine side chain and their binding affinities for estrogen receptors are described. These compounds bearing piperazine side chains were identified to be high-affinity ligands with high selectivity for ER
Synergistic methodologies for the synthesis of 3-aroyl-2- arylbenzo[b]thiophene-based selective estrogen receptor modulators. Two concise syntheses of raloxifene
Bradley, David A.,Godfrey, Alexander G.,Schmid, Christopher R.
, p. 5155 - 5159 (2007/10/03)
Difunctionalized benzo[b]thiophene intermediates are prepared which allow fully independent elaboration of the 2-aryl position or the tether position of benzo[b]thiophene-based selective estrogen receptor modulators (SERMs). Two concise syntheses of the SERM raloxifene (Evista) are presented.
Nucleophilic aromatic substitution on 3-aroyl-2-arylbenzothiophenes. Rapid access to raloxifene and other selective estrogen receptor modulators
Schmid, Christopher R.,Sluka, James P.,Duke, Kristin M.
, p. 675 - 678 (2007/10/03)
Versatile, mild and high yielding methods for nucleophilic aromatic substitution of 2-dialkylamino-1-ethoxides and related nucleophiles on 3- aroyl-2-arylbenzothiophene nuclei are presented. A short synthesis of raloxifene is detailed.
Substituted benzo(b)thiophene compounds having activity as selective estrogen receptor modulators
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, (2008/06/13)
The present invention provides compounds with nitrogen, sulfur or carbon linked basic side chains of formula where R1and R2are independently hydrogen, halo, hydroxy, alkoxy, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, arylca
