92014-01-2Relevant academic research and scientific papers
Synthesis of 2-Substituted Benzothio(seleno)phenes and Indoles via Ag-Catalyzed Cyclization/Demethylation of 2-Alkynylthio(seleno)anisoles and 2-Alkynyldimethylanilines
Cai, Tao,Feng, Chengjie,Shen, Fangqi,Bian, Kejun,Wu, Chunlei,Shen, Runpu,Gao, Yuzhen
, p. 653 - 656 (2020/12/23)
An Ag-catalyzed cyclization/demethylation of 2-alkynylthio(seleno)anisoles and 2-alkynyldimethylanilines is described and applied for the construction of valuable benzothio(seleno)phenes as well as indoles. Various 2-substituted benzothio(seleno)phenes and indoles were obtained in good to excellent yields under mild reaction conditions with low catalyst loading. An application of this new method is also exemplified with a concise synthesis of a bioactive molecule precursor. Furthermore, a conceivable reaction mechanism is proposed with supports from isotope-exchange experiments.
Concise synthesis and biological evaluation of 2-Aryl-3-Anilinobenzo[b]thiophene derivatives as potent apoptosis-inducing agents
Romagnoli, Romeo,Preti, Delia,Hamel, Ernest,Bortolozzi, Roberta,Viola, Giampietro,Brancale, Andrea,Ferla, Salvatore,Morciano, Giampaolo,Pinton, Paolo
, (2021/05/06)
Many clinically used agents active in cancer chemotherapy exert their activity through the induction of cell death (apoptosis) by targeting microtubules, altering protein function or inhibiting DNA synthesis. The benzo[b]thiophene scaffold holds a pivotal place as a pharmacophore for the development of anticancer agents, and, in addition, this scaffold has many pharmacological activities. We have developed a flexible method for the construction of a new series of 2-aryl-3-(3,4,5-trimethoxyanilino)-6-methoxybenzo[b]thiophenes as potent antiproliferative agents, giving access to a wide range of substitution patterns at the 2-position of the 6-methoxybenzo[b]thiophene common intermediate. In the present study, all the synthesized compounds retained the 3-(3,4,5-trimethoxyanilino)-6-methoxybenzo[b]thiophene moiety, and the structure–activity relationship was examined by modification of the aryl group at its 2-position with electron-withdrawing (F) or electron-releasing (alkyl and alkoxy) groups. We found that small substituents, such as fluorine or methyl, could be placed in the para-position of the 2-phenyl ring, and these modifications only slightly reduced antiproliferative activity relative to the unsubstituted 2-phenyl analogue. Compounds 3a and 3b, bearing the phenyl and para-fluorophenyl at the 2-position of the 6-methoxybenzo[b]thiophene nucleus, respectively, exhibited the greatest antiproliferative activity among the tested compounds. The treatment of both Caco2 (not metastatic) and HCT-116 (metastatic) colon carcinoma cells with 3a or 3b triggered a significant induction of apoptosis as demonstrated by the increased expression of cleaved-poly(ADP-ribose) polymerase (PARP), receptor-interacting protein (RIP) and caspase-3 proteins. The same effect was not observed with non-transformed colon 841 CoN cells. A potential additional effect during mitosis for 3a in metastatic cells and for 3b in non-metastatic cells was also observed.
Nickel-catalyzed and Li-mediated regiospecific C-H arylation of benzothiophenes
Canivet, Jér?me,Grousset, Léonie,Hisler, Ga?lle,Mohr, Yorck,Quadrelli, Elsje Alessandra,Roux, Yoann,Wisser, Florian M.
, p. 3155 - 3161 (2020/06/19)
A nickel-based catalytic system for the regiospecific C2-H arylation of benzothiophene has been established. NiCl2(bpy) is used as a catalyst in combination with LiHMDS as a base in dioxane. The catalytic system is applicable to a variety of functionalized benzothiophenes, as well as other heteroarenes including thiophene, benzodithiophene, benzofuran and selenophene in combination with iodo aryl electrophiles. The role of LiHMDS as a uniquely potent base and a postulated mechanism are discussed. The applicability of this system is finally demonstrated for the synthesis of an intermediate of an active pharmaceutical ingredient.
Discovery of LSZ102, a potent, orally bioavailable selective estrogen receptor degrader (SERD) for the treatment of estrogen receptor positive breast cancer
Tria, George S.,Abrams, Tinya,Baird, Jason,Burks, Heather E.,Firestone, Brant,Gaither, L. Alex,Hamann, Lawrence G.,He, Guo,Kirby, Christina A.,Kim, Sunkyu,Lombardo, Franco,Macchi, Kaitlin J.,McDonnell, Donald P.,Mishina, Yuji,Norris, John D.,Nunez, Jill,Springer, Clayton,Sun, Yingchuan,Thomsen, Noel M.,Wang, Chunrong,Wang, Jianling,Yu, Bing,Tiong-Yip, Choi-Lai,Peukert, Stefan
supporting information, p. 2837 - 2864 (2018/04/23)
In breast cancer, estrogen receptor alpha (ERα) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERα positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochemical properties. We describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs. This article culminates in the identification of LSZ102 (10), a compound in clinical development for the treatment of ERα positive breast cancer.
MODULATORS OF ESTROGEN RECEPTOR PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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Paragraph 00399, (2018/08/20)
The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
HYDROPHOBIC COMPOUNDS FOR OPTICALLY ACTIVE DEVICES
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Paragraph 150; 288; 289, (2018/09/12)
The present invention relates to novel compounds (I) particularly to compounds comprising a photoactive unit, said novel compounds being particularly suitable for compositions and ophthalmic devices as well as to compositions and ophthalmic devices compri
Preparation of Benzothiophenes and Benzoselenophenes from Arylamines and Alkynes via Radical Cascade Reactions
Zang, Hao,Sun, Jian-Guo,Dong, Xin,Li, Ping,Zhang, Bo
, p. 1746 - 1752 (2016/06/09)
An intermolecular radical cascade reaction between readily prepared o-methylthio-arylamines or o-methylselanyl-arylamines and alkynes for the preparation of valuable benzothiophenes or benzoselenophenes is reported. These transformations occur efficiently with complete regioselectivity and the products are obtained in moderate to good yields. The current protocol is successfully applied to the synthesis of the key intermediates of the drug raloxifene and an AT1receptor antagonist.
COMPOUNDS AND COMPOSITIONS AS SELECTIVE ESTROGEN RECEPTOR DEGRADERS
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Paragraph 0255; 0258; 0259; 260, (2014/09/03)
The present invention relates to compounds of formula I: in which n, m, X, Y1, R1, R2, R3, R4 and R5 are defined in the Summary of the Invention; capable of being both potent antagonists and degraders of estrogen receptors. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with aberrant estrogen receptor activity.
Transition-metal-free method for the synthesis of benzo[b]thiophenes from o -halovinylbenzenes and K2S via direct SNAr-type reaction, cyclization, and dehydrogenation process
Zhang, Xiaoyun,Zeng, Weilan,Yang, Yuan,Huang, Hui,Liang, Yun
supporting information, p. 1687 - 1692 (2013/09/02)
A new, highly efficient procedure for the synthesis of benzothiophenes from easily available o-halovinylbenzenes and potassium sulfide has been developed. The reaction tolerated a wide range of functionalities, and various 2-substituted benzo[b]thiophenes
Visible light photocatalytic synthesis of benzothiophenes
Hari, Durga Prasad,Hering, Thea,Koenig, Burkhard
, p. 5334 - 5337,4 (2012/12/12)
The photocatalytic reaction of o-methylthio-arenediazonium salts with alkynes yields substituted benzothiophenes regioselectively through a radical annulation process. Green light irradiation of eosin Y initiates the photoredox catalysis. The scope of the reaction was investigated by using various substituted diazonium salts and different alkynes.
