methyl 5-(4-bromophenyl)pent-4-ynoate | 1369558-71-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 5-(4-bromophenyl)pent-4-ynoate
• 英文别名: methyl 5-(4-bromophenyl)-4-pentynoate
• CAS: 1369558-71-3
• 化学式: C₁₂H₁₁BrO₂
• 分子量: 267.122
• InChiKey: LVIIUQSYDVDBCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 5-(4-bromophenyl)pent-4-ynoate 在 potassium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 C₁₁H₉BrO₂
  参考文献：
  名称：

  Gold-Catalyzed Cycloisomerization of 1,6-Diyne Carbonates and Esters to 2,4a-Dihydro-1H-fluorenes

  摘要：

  A synthetic method to prepare 2,4a-dihydro-1H-fluorenes efficiently from gold(I)-catalyzed 1,2-acyloxy migration/cyclopropenation/Nazarov cyclization of 1,6-diyne carbonates and esters is described. The suggested reaction pathway provides rare examples of [2,3]-sigmatropic rearrangement in this class of compounds as well as the involvement of an in situ formed cyclopropene intermediate in gold catalysis. Experimental and ONIOM(QM:QM') [our own n-layered integrated molecular orbital and molecular mechanics(quantum mechanics quantum mechanics')] computational studies based on the proposed Au carbenoid species provide insight into this unique selectivity.

  DOI：

  10.1021/ja4032727
• 作为产物：
  描述：

  (4-溴苯基乙炔基)三甲基硅烷 、 丙烯酸甲酯（MA） 在 indium(III) chloride 、 三乙胺 作用下， 以 氯苯 为溶剂， 反应 24.0h， 以75%的产率得到methyl 5-(4-bromophenyl)pent-4-ynoate
  参考文献：
  名称：

  氯化铟（III）催化炔烷基硅烷与丙烯酸酯的共轭加成反应

  摘要：

  已经开发了在催化量的氯化铟（III）存在下通过将炔基硅烷共轭加成到丙烯酸酯上来合成δ，γ-炔基酯的新颖有效的方法。该方法提供了快速有效地获得取代的δ，γ-炔基酯的方法。

  DOI：

  10.1021/jo202628c

文献信息

• Discovery of Potent, Selective, and Orally Bioavailable Estrogen-Related Receptor-γ Inverse Agonists To Restore the Sodium Iodide Symporter Function in Anaplastic Thyroid Cancer
  作者：Jina Kim、Jaeyoung Song、Hyun Dong Ji、Eun Kyung Yoo、Jae-Eon Lee、Sang Bong Lee、Ji Min Oh、Seungmi Lee、Ji Sun Hwang、Heeseok Yoon、Dong-Su Kim、Su-Jeong Lee、Minseon Jeong、Sungwoo Lee、Kyung-Hee Kim、Hueng-Sik Choi、Sang Woo Lee、Keun-Gyu Park、In-Kyu Lee、Seong Heon Kim、Hayoung Hwang、Yong Hyun Jeon、Jungwook Chin、Sung Jin Cho

  DOI：10.1021/acs.jmedchem.8b01296

  日期：2019.2.28

  An inverse agonist of estrogen-related receptor-gamma (ERR gamma), an orphan nuclear receptor encoded by Esrrg, enhances sodium iodide symporter-mediated radioiodine uptake in anaplastic thyroid cancer (ATC) cells, thereby facilitating responsiveness to radioiodine therapy in vitro. We synthesized potent, selective, and orally bioavailable ERR gamma-inverse agonists and evaluated their activity by analyzing in vitro pharmacology and absorption, distribution, metabolism, excretion, and toxicity profiles. X-ray crystallographic analysis of the ligand and ERR gamma complex showed that 35 completely binds to the target protein (PDB 6A6K). Our results showed improved radioiodine avidity in ATC cells through compound 35 mediated upregulation of iodide-handling genes, leading to enhanced responsiveness to radioiodine therapy in vitro. Importantly, in vivo I-124-positron emission tomography/computed tomography imaging revealed that 35 increases radioiodine avidity in CAL62 tumors. Collectively, these results demonstrated that 35 can be developed as a promising treatment for ERR gamma-related cancer in the future.
• Insights of a Lead Optimization Study and Biological Evaluation of Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists
  作者：Jina Kim、Seo Yeon Woo、Chun Young Im、Eun Kyung Yoo、Seungmi Lee、Hyo-Ji Kim、Hee-Jong Hwang、Joong-heui Cho、Won Seok Lee、Heeseok Yoon、Shinae Kim、Oh-bin Kwon、Hayoung Hwang、Kyung-Hee Kim、Jae-Han Jeon、Thoudam Debraj Singh、Sang Wook Kim、Sung Yeoun Hwang、Hueng-Sik Choi、In-Kyu Lee、Seong Heon Kim、Yong Hyun Jeon、Jungwook Chin、Sung Jin Cho

  DOI：10.1021/acs.jmedchem.6b01204

  日期：2016.11.23

  We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERR gamma but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had comparable potency to 3 and were far more selective for ERR gamma over the ERR alpha, -beta, and ER alpha. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds. Additionally, we observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in 6g- or 10b treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, 6g and 10b-possess advantageous druglike properties and can be used to potentially treat various ERR gamma-related disorders.
• Synthesis and biological evaluation of novel 4-hydroxytamoxifen analogs as estrogen-related receptor gamma inverse agonists
  作者：Jina Kim、Jungwook Chin、Chun Young Im、Eun Kyung Yoo、Seoyeon Woo、Hee Jong Hwang、Joong-heui Cho、Kyung-ah Seo、Jaeyoung Song、Hayoung Hwang、Kyung-Hee Kim、Nam Doo Kim、Suk Kyoon Yoon、Jae-Han Jeon、Seung-Yun Yoon、Yong Hyun Jeon、Hueng-Sik Choi、In-Kyu Lee、Seong Heon Kim、Sung Jin Cho

  DOI：10.1016/j.ejmech.2016.04.076

  日期：2016.9

  Estrogen-related receptor gamma (ERRγ) has recently been recognized as an attractive target for treating inflammation, cancer, and metabolic disorders. Herein, we discovered and demonstrated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that could act as highly selective inverse agonists for ERRγ. The results were comparable to those for GSK5182 (4), a leading ERRγ inverse agonist ligand. Briefly, the half-maximal inhibitory concentration (IC50) range of the synthesized compounds for ERRγ was 0.1-10 μM. Impressively, compound 24e exhibited potency comparable to 4 but was more selective for ERRγ over three other subtypes: ERRα, ERRβ, and estrogen receptor α. Furthermore, compound 24e exhibited a superior in vitro ADMET profile compared to the other compounds. Thus, the newly synthesized class of ERRγ inverse agonists could be lead candidates for developing clinical therapies for ERRγ-related disorders.
• An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer
  作者：Jina Kim、Hayoung Hwang、Heeseok Yoon、Jae-Eon Lee、Ji Min Oh、Hongchan An、Hyun Dong Ji、Seungmi Lee、Eunju Cha、Min Jung Ma、Dong-Su Kim、Su-Jeong Lee、Tara Man Kadayat、Jaeyoung Song、Sang Woo Lee、Jae-Han Jeon、Keun-Gyu Park、In-Kyu Lee、Yong Hyun Jeon、Jungwook Chin、Sung Jin Cho

  DOI：10.1016/j.ejmech.2020.112501

  日期：2020.11

  Estrogen-related receptor gamma (ERR gamma) is the NR3B subgroup of associated transcription factors. In this report, a new generation of a potent and selective ERR gamma inverse agonist (25) with good biocompatibility was proposed. We also explored the potential of the newly developed compound 25 in the PDTC model to expand the original indications from ATC. In addition, an X-ray crystallographic study of the ligand and ERR gamma co-complex showed that 25 completely binds to the target protein (PDB 6KNR). Its medicinal chemistry, including a distinctive structural study to in vivo results, denotes that 25 may be directed towards the development of a pivotal treatment for ERR gamma-related cancers. (C) 2020 Elsevier Masson SAS. All rights reserved.
• Gold-Catalyzed Cycloisomerization of 1,6-Diyne Carbonates and Esters to 2,4a-Dihydro-1<i>H</i>-fluorenes
  作者：Weidong Rao、Ming Joo Koh、Dan Li、Hajime Hirao、Philip Wai Hong Chan

  DOI：10.1021/ja4032727

  日期：2013.5.29

  A synthetic method to prepare 2,4a-dihydro-1H-fluorenes efficiently from gold(I)-catalyzed 1,2-acyloxy migration/cyclopropenation/Nazarov cyclization of 1,6-diyne carbonates and esters is described. The suggested reaction pathway provides rare examples of [2,3]-sigmatropic rearrangement in this class of compounds as well as the involvement of an in situ formed cyclopropene intermediate in gold catalysis. Experimental and ONIOM(QM:QM') [our own n-layered integrated molecular orbital and molecular mechanics(quantum mechanics quantum mechanics')] computational studies based on the proposed Au carbenoid species provide insight into this unique selectivity.