methyl (E)-4-(geranyloxy)cinnamate | 111017-07-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl (E)-4-(geranyloxy)cinnamate
• 英文别名: Methyl cis-p-coumarate 3-(3,7-dimethyl-2,6-octadienyl)；methyl (E)-3-[4-[(2E)-3,7-dimethylocta-2,6-dienoxy]phenyl]prop-2-enoate
• CAS: 111017-07-3
• 化学式: C₂₀H₂₆O₃
• 分子量: 314.425
• InChiKey: KSSYIBXTLHIBBX-OZZAOFPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (E)-4-(geranyloxy)cinnamate 在 4-二甲氨基吡啶 、 水 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 (E)-S-2-acetamidoethyl 3-{4-[(E)-3,7-dimethylocta-2,6-dienyloxy]-phenyl}prop-2-enethioate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New Cinnamic Derivatives as Antituberculosis Agents

  摘要：

  Tuberculosis, HIV coinfection with TB, emergence of multidrug-resistant TB, and extensively drug-resistant TB are the major causes of death from infectious diseases worldwide. Because no new drug has been introduced in the last several decades, new classes of molecules as anti-TB drugs are urgently needed. Herein, we report the synthesis and structure-activity relationships of a series of thioester, amide, hydrazide, and triazolophthalazine derivatives of 4-alkoxy cinnamic acid. Many compounds exhibited submicromolar minimum inhibitory concentrations against Mycobacterium tuberculosis strain (H(37)Rv). Interestingly, compound 13e, a 4-isopentenyloxycinnamyl triazolophthalazine derivative, was found to be 100-1800 times more active than isoniazid (INH) when tested for its ability to inhibit the growth of INH-resistant M. tuberculosis strains. The results also revealed that 13e does not interfere with mycolic acid biosynthesis, thereby pointing to a different mode of action and representing an attractive lead compound for the development of new anti-TB agents.

  DOI：

  10.1021/jm101510d
• 作为产物：
  描述：

  4-香豆酸 在 硫酸 、 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 44.0h， 生成 methyl (E)-4-(geranyloxy)cinnamate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New Cinnamic Derivatives as Antituberculosis Agents

  摘要：

  Tuberculosis, HIV coinfection with TB, emergence of multidrug-resistant TB, and extensively drug-resistant TB are the major causes of death from infectious diseases worldwide. Because no new drug has been introduced in the last several decades, new classes of molecules as anti-TB drugs are urgently needed. Herein, we report the synthesis and structure-activity relationships of a series of thioester, amide, hydrazide, and triazolophthalazine derivatives of 4-alkoxy cinnamic acid. Many compounds exhibited submicromolar minimum inhibitory concentrations against Mycobacterium tuberculosis strain (H(37)Rv). Interestingly, compound 13e, a 4-isopentenyloxycinnamyl triazolophthalazine derivative, was found to be 100-1800 times more active than isoniazid (INH) when tested for its ability to inhibit the growth of INH-resistant M. tuberculosis strains. The results also revealed that 13e does not interfere with mycolic acid biosynthesis, thereby pointing to a different mode of action and representing an attractive lead compound for the development of new anti-TB agents.

  DOI：

  10.1021/jm101510d

文献信息

• Organic synthesis using haloboration reaction XVIII. A stereoselective synthesis of β—mono- and β,β-disubstituted α,β-unsaturated esters
  作者：Naoko Yamashina、Satoshi Hyuga、Shoji Hara、Akira Suzuki

  DOI：10.1016/s0040-4039(01)89020-1

  日期：1989.1

  β—Mono- and β,β—disubstituted α,β-unsaturated esters can be prepared in good yields stereoselectively by the stepwise alkylation and alkoxycarbonylation of 2-bromo-1-alkenylboronates.

  通过2-溴-1-链烯基硼酸酯的逐步烷基化和烷氧羰基化，可以立体选择性地高产率地制备β-单-和β，β-二取代的α，β-不饱和酯。
• Discovery and development of CPL207280 as new GPR40/FFA1 agonist
  作者：Mateusz Mach、Katarzyna Bazydło-Guzenda、Paweł Buda、Mikołaj Matłoka、Radosław Dzida、Filip Stelmach、Kinga Gałązka、Małgorzata Wąsińska-Kałwa、Damian Smuga、Dagmara Hołowińska、Urszula Dawid、Lidia Gurba-Bryśkiewicz、Krzysztof Wiśniewski、Krzysztof Dubiel、Jerzy Pieczykolan、Maciej Wieczorek

  DOI：10.1016/j.ejmech.2021.113810

  日期：2021.12

  unique mechanism that limits the possibility of hypoglycemia, the free fatty acid receptor (FFA1) is an attractive target for the treatment of type 2 diabetes. So far, however, none of the promising agonists have been able to enter the market. The most advanced clinical candidate, TAK-875, was withdrawn from phase III clinical trials due to liver safety issues. In this article, we describe the key aspects

  由于限制低血糖可能性的独特机制，游离脂肪酸受体 (FFA1) 是治疗 2 型糖尿病的有吸引力的靶标。然而，到目前为止，没有一个有前途的激动剂能够进入市场。由于肝脏安全问题，最先进的临床候选药物 TAK-875 退出了 III 期临床试验。在本文中，我们描述了导致发现 CPL207280 ( 13 ) 的关键方面，其设计侧重于长期安全性。引入小的、受自然启发的无环结构片段导致化合物具有保留的高效力和令人满意的药代动力学特征。优化的合成和放大提供了稳定的固体形式的 CPL207280-51 ( 45) 具有毒理学研究和正在进行的临床试验所需的特性。
• Synthesis and anticancer activity evaluation of 2(4-alkoxyphenyl)cyclopropyl hydrazides and triazolo phthalazines
  作者：Prithwiraj De、Michel Baltas、Delphine Lamoral-Theys、Céline Bruyère、Robert Kiss、Florence Bedos-Belval、Nathalie Saffon

  DOI：10.1016/j.bmc.2010.02.041

  日期：2010.4

  A series of new 2(4-alkoxyphenyl) cyclopropyl hydrazide-and triazolo-derivatives were synthesized starting from 4-hydroxycinnamic acid (1) in a clean, mild, efficient and straightforward synthetic protocol. These compounds consisting of different alkoxy substitution, phenylcyclopropyl backbone and different heterocyclic groups were evaluated for in vitro anticancer activity against 4 cell lines displaying certain levels of resistance to pro-apoptotic stimuli and 2 cell lines sensitive to pro-apoptotic compounds. Compounds 7f and 8e were most active and displaying moderate in vitro cytostatic effect through different mechanisms. Significantly, chemically modified derivatives could be obtained in order to develop novel types of compounds aiming to combat apoptosis-resistant cancers, for example, those cancers associated with dismal prognoses. (C) 2010 Elsevier Ltd. All rights reserved.
• Weyerstahl, Peter; Marschall, Helga; Bork, Wolf-Rainer, Liebigs Annalen der Chemie, 1994, # 10, p. 1043 - 1048
  作者：Weyerstahl, Peter、Marschall, Helga、Bork, Wolf-Rainer、Rilk, Rainer

  DOI：——

  日期：——
• In vitro inhibitory activity of boropinic acid against Helicobacter pylori
  作者：Francesco Epifano、Luigi Menghini、Rita Pagiotti、Paola Angelini、Salvatore Genovese、Massimo Curini

  DOI：10.1016/j.bmcl.2006.08.043

  日期：2006.11

  In this study, we assessed in vitro minimum inhibitory concentration (MIC) values of some natural geranyloxycoumarins, geranyloxy- and isopentenyloxy acids against growth of Helicobacter pylori. Boropinic acid, active principle isolated from Boronia pinnata (Fam. Rutaceae), was seen to be the most effective compound with a MIC value of 1.62 mu g/mL. (c) 2006 Elsevier Ltd. All rights reserved.