An expeditious synthesis of tamoxifen, a representative SERM (selective estrogen receptor modulator), via the three-component coupling reaction among aromatic aldehyde, cinnamyltrimethylsilane, and β-chlorophenetole

Shiina, Isamu; Sano, Yoshiyuki; Nakata, Kenya; Suzuki, Masahiko; Yokoyama, Toshikazu; Sasaki, Akane; Orikasa, Tomoko; Miyamoto, Tomomi; Ikekita, Masahiko; Nagahara, Yukitoshi; Hasome, Yoshimune

doi:10.1016/j.bmc.2007.09.008

Cited by 23 publications

(33 citation statements)

References 46 publications

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“…The final products 10 were obtained after hydrogenolysis, demethylation, and halogenation. [42][43][44] To further determine the importance of the D-ring and the aromatic property of the C-ring, additional D-ring deletion analogues were synthesized. These analogues use a 4-phenylnaphthalene scaffold (II, Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Rose Bengal Analogues as SecA Inhibitors

et al. 2013

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SecA, a key component of bacterial Sec-dependent secretion pathway, is an attractive target for exploring novel antimicrobials. Rose bengal (RB), a polyhalogenated fluorescein derivative, was found from our previous study as a potent SecA inhibitor. Here we describe the synthesis and structure-activity relationships (SAR) of 23 RB analogues that were designed by systematical dissection of RB. Evaluation of these analogues allowed us to establish an initial SAR in SecA inhibition. The antimicrobial effects of these SecA inhibitors are confirmed in experiments using E. coli and B. subtilis.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Rose Bengal Analogues as SecA Inhibitors

et al. 2013

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“…Tamoxifen and its derivatives ( Fig. 1) were synthesized chemically in our laboratory based on the methods described by Shiina et al (18)(19)(20)(21) Medium and cell cultures. Cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum and 75 mg/ L kanamycin sulfate, and maintained at 37°C in a humidified chamber under an atmosphere of 95% air and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…1) were synthesized chemically in our laboratory based on the methods described by Shiina et al . ( 18–21 )…”

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confidence: 99%

Induction of mitochondria‐involved apoptosis in estrogen receptor‐negative cells by a novel tamoxifen derivative, ridaifen‐B

et al. 2008

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Tamoxifen is an antagonist of estrogen receptor, which is used widely as an estrogen receptor-positive breast cancer drug that blocks growth signals and provokes apoptosis. However, recent studies have revealed that tamoxifen induces apoptosis even in estrogen receptor-negative cells. In the present study, we synthesized several tamoxifen derivatives to augment the apoptosis-inducing effect of tamoxifen and evaluated the apoptosis-inducing pathway. The estrogen receptor-positive human leukemia cell line HL-60 and estrogen receptor-negative human leukemia cell line Jurkat were treated with tamoxifen and synthesized tamoxifen derivatives, and thereafter subjected to cell viability-detection assays. Tamoxifen derivatives, as well as the lead compound tamoxifen, decreased the cell viability despite the expression of estrogen receptor. Among all of the synthesized tamoxifen derivatives, ridaifen-B had more potent cancer cell-damaging activity than tamoxifen. Ridaifen-B fragmented Jurkat cell DNA and activated caspases, suggesting that the ridaifen-B-induced apoptosis pathway is estrogen receptor independent. Moreover, mitochondrial involvement during ridaifen-B-induced apoptosis was estimated. Ridaifen-B significantly reduced mitochondrial membrane potential, and overexpression of Bcl-2 inhibited ridaifen-B-induced apoptosis. These results suggest that the induction of apoptosis by ridaifen-B, a novel tamoxifen derivative, is dependent on mitochondrial perturbation without estrogen receptor involvement. (Cancer Sci 2008; 99: 608-614) O ne way of enhancing the ability of cancer cells to multiply is by utilizing growth factor receptors, as well as growth hormone receptors, to effectively receive cellular growth signals. One of the hormone receptors, ER, is expressed in most breast cancer cells. ER has two subtypes, ER-α and ER-β. ER-α is a transcription factor that induces not only growth-promoting genes but also differentiation-related genes, (1,2) resulting in the mediation of reproduction, metabolism, and cancer-cell growth. Another ER subtype, ER-β, was cloned in 1996, (3) and has a ligand-binding domain identical to that of ER-α. However, the physiological effect of ER-β seems to be the opposite of that of ER-α: it inhibits proliferation.(4) The non-steroidal SERM TAM binds to ER instead of the endogenous growth hormone estrogen 17β-estradiol, leading to inhibition of breast cancer cell proliferation and resulting in apoptosis.(5) Therefore, TAM is now used widely as an ER-positive breast cancer drug. However, how TAM induces apoptosis, which is the pharmacological effect of TAM, is obscure as several reports have demonstrated that a high dose and long time treatment with TAM is able to induce apoptosis even in ER-negative cancer cells.(6,7) TAM therefore seems to induce apoptosis in both ER-positive and -negative cells, suggesting that ER is not necessary for TAM to provoke a cancer-cell decrease.Mitochondria play an important role in apoptosis. With multiple cytotoxic stimuli, including UV, X-ray, and many chemi...

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“…The combined organic phases were dried over anhydrous sodium sulfate and evaporated to dryness in vacuo. The crude mixture was purified via flash chromatography (ethyl acetate) to afford the desired product as an off-white resin (94%, Z/E = 3.5/1) 55 …”

Section: (E)-4-(8-fluoro-5-(4-styrylphenyl)-23-dihydrobenzo[b]oxepinmentioning

confidence: 99%

Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity

et al. 2017

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Estrogen receptor ERis an important target for the design of drugs such as tamoxifen (2a) and fulvestrant (5). Three series of ER-ligands based on the benzoxepin scaffold structure were 2 synthesised -series I containing an acrylic acid, series II with an acrylamide and series III with a saturated carboxylic acid substituent. These compounds were shown to be high affinity ligands for the ER with nanomolar IC50 binding values. Series I acrylic acid ligands were generally ER selective. In particular, compound 13e featuring a phenylpenta-2,4-dienoic acid substituent was shown to be antiproliferative and downregulated ERand ER expression in MCF-7 breast cancer cells. Interestingly, from series III, the phenoxybutyric acid derivative compound 22 was not antiproliferative and selectively downregulated ER. A docking study of the benzoxepin ligands was undertaken. Compound 13e is a promising lead for development as a clinically relevant SERD, whilst compound 22 will be a useful experimental probe for helping to elucidate the role of ERβ in cancer cells.

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An expeditious synthesis of tamoxifen, a representative SERM (selective estrogen receptor modulator), via the three-component coupling reaction among aromatic aldehyde, cinnamyltrimethylsilane, and β-chlorophenetole

Cited by 23 publications

References 46 publications

Design, Synthesis and Biological Evaluation of Rose Bengal Analogues as SecA Inhibitors

Design, Synthesis and Biological Evaluation of Rose Bengal Analogues as SecA Inhibitors

Induction of mitochondria‐involved apoptosis in estrogen receptor‐negative cells by a novel tamoxifen derivative, ridaifen‐B

Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity

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