6-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)oxy)-2H-chromen-2-one | 1415658-74-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 6-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)oxy)-2H-chromen-2-one
• 英文别名: 6-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienoxy]chromen-2-one
• CAS: 1415658-74-0
• 化学式: C₂₄H₃₀O₃
• 分子量: 366.5
• InChiKey: JAASWVRGXJPPHR-WOWYBKFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-羟基香豆素 、 反,反-法呢基溴 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 12.0h， 生成 6-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)oxy)-2H-chromen-2-one
  参考文献：
  名称：

  O-异戊二烯化喹诺酮作为一类新型 15-脂氧合酶抑制剂：合成、表征和抑制评估

  摘要：

  动物和植物中不饱和脂质的催化过氧化与 15-脂氧合酶的活性密切相关。众所周知，脂氧合酶 (LOX) 在许多急性和慢性综合征中发挥着重要作用，例如炎症、哮喘、癌症和过敏。在本研究中，合成了一系列单异戊二烯氧基喹啉，并评估其作为大豆15-脂氧合酶（SLO）的潜在抑制剂，并将其抑制效力与先前报道的单异戊二烯氧基香豆素进行了比较。合成化合物通过竞争机制抑制脂氧合酶，如异戊二烯氧基香豆素。结果表明异戊烯基部分的位置和长度在脂氧合酶抑制活性中起着重要作用。在所有合成化合物（香豆素和喹诺酮衍生物）中，5-法呢基氧基香豆素和8-法呢基氧基喹诺酮表现出最佳的抑制活性，IC 50值分别为1.1 µM 和0.53 µM。

  DOI：

  10.1111/cbdd.13944

文献信息

• Coumarin derivatives for cancer therapy
  申请人：Wellesley College

  公开号：US09388155B1

  公开（公告）日：2016-07-12

  The disclosure provides methods and compositions for treating and preventing cancer using 6-substituted coumarin derivatives. The coumarin derivatives of the disclosure have substituents at the 6-position with five carbon atoms or greater. The coumarin derivatives may be further substituted and may be 3,4-dihydrocoumarins. In preferred embodiments, the coumarin derivatives of the disclosure are used to treat pancreatic cancer.

  本公开提供使用6-取代香豆素衍生物治疗和预防癌症的方法和组合物。本公开的香豆素衍生物在6位具有五个或更多碳原子的取代基。香豆素衍生物可能进一步取代，并且可能是3,4-二氢香豆素。在首选实施例中，本公开的香豆素衍生物用于治疗胰腺癌。
• Identification of the Factors Responsible for the Selective <i>in vitro</i> Cytotoxic Activity of Isoprenylated Coumarin Derivatives under Nutrient-deprived Conditions
  作者：Hong Zhang、Ronghao Zhou、Maria Jun、Alyssa F. Bacay、Katherine Eyring、Andrew Webb、Dora Carrico-Moniz

  DOI：10.7150/jca.13243

  日期：——

  Pancreatic cancer is one of the most devastating forms of human cancer. The lack of effective clinical treatments for pancreatic cancer has led to one of the lowest five-year survival rates among all cancers. Recently, our laboratory has developed a novel series of isoprenylated coumarin derivatives that have exhibited anti-pancreatic cancer activity exclusively under nutrient-deprived conditions. In this study, we report the effect of the various cell culture medium components on the preferential cytotoxicity of our lead isoprenylated coumarin compound against the pancreatic adenocarcinoma cell line PANC-1. In particular, our findings show a clear link between observed cytotoxicity and glucose deprivation, suggesting that our compound targets a salvage pathway when glycolysis is no longer an option for cancer cell survival. The cytotoxicity of our lead compound was also examined in vitro against two other pancreatic cancer cell lines, BxPC-3 and Capan-2 under both nutrient-rich and nutrient-deprived conditions.

  胰腺癌是最具破坏性的人类癌症之一。由于缺乏有效的临床治疗方法，胰腺癌的五年生存率是所有癌症中最低的。最近，我们实验室开发了一系列新型异戊烯化香豆素衍生物，这些衍生物仅在营养匮乏条件下表现出抗胰腺癌活性。在本研究中，我们报告了各种细胞培养基成分对我们的领先异戊烯化香豆素化合物对胰腺癌细胞系 PANC-1 的优先细胞毒性的影响。特别是，我们的研究结果表明，观察到的细胞毒性与葡萄糖剥夺之间存在明显联系，这表明当糖酵解不再是癌细胞生存的一种选择时，我们的化合物靶向的是一种挽救途径。我们还在营养丰富和营养缺乏的条件下，在体外检测了我们的先导化合物对另外两种胰腺癌细胞系 BxPC-3 和 CaPAN-2 的细胞毒性。
• Synthesis and SAR studies of mono O-prenylated coumarins as potent 15-lipoxygenase inhibitors
  作者：Mehrdad Iranshahi、Atena Jabbari、Ala Orafaie、Robabeh Mehri、Soudabeh Zeraatkar、Taraneh Ahmadi、Maliheh Alimardani、Hamid Sadeghian

  DOI：10.1016/j.ejmech.2012.09.006

  日期：2012.11

  All of the mono isopentenyloxy, -geranyloxy and -farnesyloxy derivatives of coumarin were synthesized and their inhibitory potency against soybean 15-lipoxygenase (SLO) and human 15-lipoxygenase-1 (HLO-1) were determined. Amongst the synthetic analogs, 5-farnesyloxycoumarin showed the most potent inhibitory activity against SLO (IC50 = 0.8 mu M) while 6-farnesyloxycoumarin was the strongest HLO-1 inhibitor (IC50 = 1.3 mu M). The IC50 variations of the farnesyl derivatives for HLO-1 (1.3 to similar to 75 mu M) were much higher than that observed for SLO (0.8-5.8 mu M). SAR studies showed that hydrogen bonding, CH/pi, anion-pi and S-O=C interactions with Fe-III-OH, Leu408, Glu357 and Met419 were the distinct intermolecular interactions which can lead to important role of the coumarin substitution site in HLO-1 inhibitory potency, respectively. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of isoprenylated coumarins as potential anti-pancreatic cancer agents
  作者：Maria Jun、Alyssa F. Bacay、James Moyer、Andrew Webb、Dora Carrico-Moniz

  DOI：10.1016/j.bmcl.2014.08.038

  日期：2014.10

  A series of isoprenylated coumarins has been designed, synthesized, and evaluated against human pancreatic adenocarcinoma cell line PANC-1 under nutrient-rich and nutrient-deprived conditions. The compounds described investigate the effect of isoprenyl chain length and positioning on cell growth inhibition. The majority of these compounds displayed cytotoxicity against PANC-1 cells selectively in the absence of essential amino acids, glucose, and serum, and showed no cytotoxicity under nutrient-rich conditions. In this study, compound 6 exhibited the highest cytotoxic activity with an LC50 value of 4μM and induced apoptosis-like morphological changes in PANC-1 cells after a 24-h incubation. The evaluated structure-activity relationships show that substitution at the 6-position and the presence of a farnesyl isoprenyl tail are important structural features for enhanced preferential cytotoxicity. These findings provide important information to designing other structural analogues for potential application as novel pancreatic antitumor agents.
• US9388155B1
  申请人：——

  公开号：US9388155B1

  公开（公告）日：2016-07-12