6-氟-3-羟基异苯并呋喃-1(3h)-酮 | 105398-58-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 中文名称: 6-氟-3-羟基异苯并呋喃-1(3h)-酮
• 英文名称: 6-fluoro-3-hydroxyisobenzofuran-1(3H)-one
• 英文别名: 6-fluoro-3-hydroxy-3H-2-benzofuran-1-one
• CAS: 105398-58-1
• 化学式: C₈H₅FO₃
• 分子量: 168.124
• InChiKey: PZIAMZVABBTWEZ-UHFFFAOYSA-N

物化性质

• 沸点：
  366.8±42.0 °C(Predicted)
• 密度：
  1.567±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-氟-3-羟基异苯并呋喃-1(3h)-酮 在 sodium methylate 作用下， 以 甲醇 、 氯仿 、 乙酸乙酯 为溶剂， 反应 34.0h， 生成 (S)-3-fluoro-5,6-dihydro-6-(2,3-dihydroxypropyl)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
  参考文献：
  名称：

  Discovery of Potent Indenoisoquinoline Topoisomerase I Poisons Lacking the 3-Nitro Toxicophore

  摘要：

  3-Nitroindenoisoquinoline human topoisomerase IB (Top1) poisons have potent antiproliferative effects on cancer cells. The undesirable nitro toxicophore could hypothetically be replaced by other functional groups that would retain the desired biological activities and minimize potential safety risks. Eleven series of indenoisoquinolines bearing 3-nitro bioisosteres were synthesized. The molecules were evaluated in the Top1-mediated DNA cleavage assay and in the National Cancer Institute's 60 cell line cytotoxicity assay. The data reveal that fluorine and chlorine may substitute for the 3-nitro group with minimal loss of Top1 poisoning activity. The new information gained from these efforts can be used to design novel indenoisoquinolines with improved safety.

  DOI：

  10.1021/acs.jmedchem.5b00303
• 作为产物：
  描述：

  3-bromo-6-fluoroisobenzofuran-1(3H)-one 在 水 作用下， 反应 1.0h， 生成 6-氟-3-羟基异苯并呋喃-1(3h)-酮
  参考文献：
  名称：

  手性双环咪唑催化的酰基动力学动力学拆分合成手性邻苯二甲酰基酯

  摘要：

  利用手性双环咪唑有机催化剂并采用连续注射工艺，已开发出另一种途径，可通过对映选择性酰化作用（3-99％ee）动态动力学拆分3-羟基邻苯二酚来有效合成手性邻苯二甲酸酯基前药。计算研究表明，一般的基础催化机理不同于广泛接受的亲核催化机理。关键过渡态的结构分析表明，催化剂与底物之间的CH-π相互作用而不是先前考虑的阳离子/π-π相互作用是引起观察到的立体控制的主要因素。

  DOI：

  10.1002/anie.202012445

文献信息

• Chiral Phosphoric Acid Catalyzed Asymmetric Ugi Reaction by Dynamic Kinetic Resolution of the Primary Multicomponent Adduct
  作者：Yun Zhang、Yu-Fei Ao、Zhi-Tang Huang、De-Xian Wang、Mei-Xiang Wang、Jieping Zhu

  DOI：10.1002/anie.201600751

  日期：2016.4.18

  Reaction of isonitriles with 3‐(arylamino)isobenzofuran‐1(3H)‐ones in the presence of a catalytic amount of an octahydro (R)‐binol‐derived chiral phosphoric acid afforded 3‐oxo‐2‐arylisoindoline‐1‐carboxamides in high yields with good to high enantioselectivities. An enantioselective Ugi four‐center three‐component reaction of 2‐formylbenzoic acids, anilines, and isonitriles was subsequently developed

  在催化量的八氢（R）-苯酚衍生的手性磷酸存在下，异腈与3-（芳基氨基）异苯并呋喃-1（3 H）-酮反应，得到3-氧代-2-芳基异吲哚啉-1-羧酰胺高收率，对映选择性好。随后开发了2-甲酰基苯甲酸，苯胺和异腈的对映选择性Ugi四中心三组分反应，用于合成相同的杂环。机理研究表明，对映选择性是由主要的Ugi加合物的动态动力学拆分引起的，而不是由C-C键形成过程引起的。所得的杂环产物具有重要的医学重要性。
• Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons
  作者：Daniel E. Beck、Wei Lv、Monica Abdelmalak、Caroline B. Plescia、Keli Agama、Christophe Marchand、Yves Pommier、Mark Cushman

  DOI：10.1016/j.bmc.2016.02.015

  日期：2016.4

  nitro group at the 3-position of indenoisoquinoline topoisomerase IB (Top1) poisons. A number of strategies were employed in the present investigation to enhance the Top1 inhibitory potencies and cancer cell growth inhibitory activities of halogenated indenoisoquinolines. In several cases, the new compounds' activities were found to rival or surpass those of similarly substituted 3-nitroindenoisoquinolines

  氟和氯在代谢上是稳定的，但通常在茚并异喹啉拓扑异构酶IB（Top1）毒物的3位上取代硝基的活性较低。在本研究中采用了多种策略来增强卤代茚并异喹啉的Top1抑制能力和癌细胞生长抑制活性。在某些情况下，发现新化合物的活性可与同类取代的3-硝基茚并异喹啉类药物媲美或超越，并通过在人类癌细胞培养物中进行测试发现了几种异常有效的类似物。发现两种卤代茚并异喹啉Top1抑制剂的内酰胺氮上的羟乙基氨基丙基侧链也具有对酪氨酰DNA磷酸二酯酶1和2（TDP1和TDP2）的抑制活性，
• 플루오로기가 치환된 프탈라지논 유도체 및 그 제조방법
  申请人：ILDONG PHARMACEUTICAL CO., LTD. 일동제약(주)(120160670930) Corp. No ▼ 110111-6139277BRN ▼803-88-00431

  公开号：KR20170037116A

  公开（公告）日：2017-04-04

  본 발명은 플루오로기가 치환된 프탈라지논 유도체, 이를 포함하는 약제학적 조성물 및 상기 프탈라지논 유도체의 제조 방법에 관한 것이다. 특히 본 발명은 폴리(ADP-리보스) 폴리머라제 효소의 활성을 억제하기 위한 프탈라지논 유도체의 약제학적 조성물에 관한 것이다.

  本发明涉及氟罗吡嗪取代的邻苯二甲酮衍生物，包括其药物组合物以及制备所述邻苯二甲酮衍生物的方法。特别是本发明涉及用于抑制聚(ADP-核糖)聚合酶酶活性的邻苯二甲酮衍生物的药物组合物。
• Synthesis and biological activity of n-butylphthalide derivatives
  作者：Wei Wang、Xue-Xiang Cha、John Reiner、Yuan Gao、Hai-Ling Qiao、Jia-Xiang Shen、Jun-Biao Chang

  DOI：10.1016/j.ejmech.2010.01.036

  日期：2010.5

  A series of n-butylphthalide derivatives were designed and synthesized. The in vitro activities of these compounds were evaluated by a resting tension of isolated rat thoracic aorta ring assay. Compounds 4g and 41 were found to be more active than n-butylphthalide. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Russel, Richard A.; Pilley, Boyd A.; Warrener, Ronald N., Synthetic Communications, 1986, vol. 16, # 4, p. 425 - 430
  作者：Russel, Richard A.、Pilley, Boyd A.、Warrener, Ronald N.

  DOI：——

  日期：——