3-fluoro-5,7-dihydroxy-4-propyl-2H-chromen-2-one | 1005323-02-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-fluoro-5,7-dihydroxy-4-propyl-2H-chromen-2-one
• 英文别名: 3-Fluoro-5,7-dihydroxy-4-propylchromen-2-one
• CAS: 1005323-02-3
• 化学式: C₁₂H₁₁FO₄
• 分子量: 238.215
• InChiKey: CGRZXFLLWUFDRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-fluoro-5,7-dihydroxy-4-propyl-2H-chromen-2-one 在 吡啶 、 aluminum (III) chloride 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  N-Oxide heterocycles and imidazoles replacing ring D of calanolides against Mycobacterium tuberculosis

  摘要：

  We have explored the chemistry of N-oxide heterocycles and imidazoles replacing ring D of the natural product (+)-calanolide A, and have synthesized 12 new analogues, two of which were active against both R Mtb and NR Mtb with MIC values of 12.5 mu g/mL, which would lead to further optimization for more potent anti-TB candidates. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.cclet.2015.11.001
• 作为产物：
  描述：

  间苯三酚 、 2-氟-3-氧代己酸乙酯 在 三氟化硼乙醚 作用下， 反应 5.0h， 以90%的产率得到3-fluoro-5,7-dihydroxy-4-propyl-2H-chromen-2-one
  参考文献：
  名称：

  N-Oxide heterocycles and imidazoles replacing ring D of calanolides against Mycobacterium tuberculosis

  摘要：

  We have explored the chemistry of N-oxide heterocycles and imidazoles replacing ring D of the natural product (+)-calanolide A, and have synthesized 12 new analogues, two of which were active against both R Mtb and NR Mtb with MIC values of 12.5 mu g/mL, which would lead to further optimization for more potent anti-TB candidates. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.cclet.2015.11.001

文献信息

• Chemical Library and Structure–Activity Relationships of 11-Demethyl-12-oxo Calanolide A Analogues as Anti-HIV-1 Agents
  作者：Tao Ma、Li Liu、Hai Xue、Li Li、Chunyan Han、Lin Wang、Zhiwei Chen、Gang Liu

  DOI：10.1021/jm701405p

  日期：2008.3.13

  (+)-Calanolide A (1) as a natural product was previously found as an inhibitor of HIV-1 reverse tratiscriptase. In our further investigation of its template, racemic 11-demethyl-12-oxo calanolide A (15), which had two fewer chiral carbon centers at the C-11 and C-12 positions than (+)-calanolide A, had a comparably inhibitory activity and better therapeutic index (EC(50) = 0.11 mu M, TI = 818) against HIV-1 in vitro. A library based on its structural core was then designed and synthesized with introduction of nine diversity points in this article. The evaluations of anti-HIV-1 activity in vitro concluded their structure-activity relationships (SARs). A novel compound (10-bromomethyl-11-demethyl-12-oxo calanolide A, 123) was identified to have much higher inhibitory potency and therapeutic index (EC(50) = 2.85 nM, TI > 10,526) than those of the class compound against HIV-1. This finding provided a very important clue that modifications of the C ring at the C-10 position may be conducted to obtain drug candidates with better activity against HIV-1.

  (+)-Calanolide A (1) 作为一种天然产物，先前被发现是HIV-1逆转录酶的抑制剂。在我们对其模板的进一步研究中，外消旋的11-去甲基-12-酮基calanolide A (15) 被发现。与(+)-calanolide A相比，它在C-11和C-12位上少两个手性碳中心，但其对HIV-1的抑制活性相当，并且具有更好的治疗指数（EC(50) = 0.11 μM，TI = 818）。随后，基于其结构核心设计并合成了一个化合物库，并在本文中引入了九个多样性点。体外评估抗HIV-1活性得出了它们的结构-活性关系（SARs）。发现了一个新的化合物（10-溴甲基-11-去甲基-12-酮基calanolide A，123），其对HIV-1的抑制效力和治疗指数（EC(50) = 2.85 nM，TI > 10,526）显著高于该类化合物。这一发现提供了非常重要的线索，即对C环的C-10位进行修饰，可能会得到对HIV-1活性更好的药物候选物。
• TETRACYCLIC DIPYRANO-COUMARIN COMPOUNDS WITH ANTI-HIV AND ANTI-MYCOBACTERIUM TUBERCULOSIS ACTIVITIES
  申请人：Liu Gang

  公开号：US20100324067A1

  公开（公告）日：2010-12-23

  The present invention relates to tetracyclodipyrano-coumarin compounds of general formula (I), wherein the substituents are defined herein. These compounds exihibit dual biological activities of anti human immunodeficiency virus type 1 (HIV-1) infection and anti- Mycobacterium Tuberculosis (TB) infection.

  本发明涉及通式（I）的四环二吡喃香豆素类化合物，其中取代基在此定义。这些化合物表现出抗人类免疫缺陷病毒类型1（HIV-1）感染和抗结核分枝杆菌（TB）感染的双重生物活性。
• TETRIACYCLODIPYRANYL COUMARINS AND THE ANTI-HIV AND ANTI-TUBERCULOSIS USES THEREOF
  申请人：Institute of Mataria Medica, Chinese Academy of Medical Sciences

  公开号：EP2216335A1

  公开（公告）日：2010-08-11

  The present invention relates to tctracyclodipyrano-coumarin compounds of general formula (I), wherein the substituents are defined herein. These compounds exihibit dual biological activities of anti human immunodeficiency virus type 1 (HIV-1) infection and anti-Mycobacterium Tuberculosis (TB) infection.

  本发明涉及通式(I)的三环二吡喃香豆素化合物，其中取代基在本文中定义。这些化合物具有抗人类免疫缺陷病毒 1 型（HIV-1）感染和抗结核分枝杆菌（TB）感染的双重生物活性。
• Synthetic Calanolides with Bactericidal Activity against Replicating and Nonreplicating <i>Mycobacterium tuberculosis</i>
  作者：Purong Zheng、Selin Somersan-Karakaya、Shichao Lu、Julia Roberts、Maneesh Pingle、Thulasi Warrier、David Little、Xiaoyong Guo、Steven J. Brickner、Carl F. Nathan、Ben Gold、Gang Liu

  DOI：10.1021/jm4019228

  日期：2014.5.8

  It is urgent to introduce new drugs for tuberculosis to shorten the prolonged course of treatment and control drug-resistant Mycobacterium tuberculosis (Mtb). One strategy toward this goal is to develop antibiotics that eradicate both replicating (R) and nonreplicating (NR) Mtb. Naturally occurring (+)-calanolide A was active against R-Mtb. The present report details the design, synthesis, antimycobacterial activities, and structure-activity relationships of synthetic calanolides. We identified potent dual-active nitro-containing calanolides with minimal in vitro toxicity that were cidal to axenic Mtb and Mtb in human macrophages, while sparing Gram-positive and -negative bacteria and yeast. Two of the nitrobenzofuran-containing lead compounds were found to be genotoxic to mammalian cells. Although genotoxicity precluded clinical progression, the profound, selective mycobactericidal activity of these calanolides will be useful in identifying pathways for killing both R- and NR-Mtb, as well as in further structure-based design of more effective and drug-like antimycobacterial agents.
• TETRACYCLODIPYRANYL COUMARINS AND THE ANTI-HIV AND ANTI-TUBERCULOSIS USES THEREOF
  申请人：Institute of Mataria Medica, Chinese Academy of Medical Sciences

  公开号：EP2216335B1

  公开（公告）日：2014-03-12