7-hydroxy-5-(2-morpholinoethoxy)-2-oxo-4-propyl-2H-chromene-8-carbaldehyde | 1604839-06-6

• 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: 7-hydroxy-5-(2-morpholinoethoxy)-2-oxo-4-propyl-2H-chromene-8-carbaldehyde
• CAS: 1604839-06-6
• 化学式: C₁₉H₂₃NO₆
• 分子量: 361.395
• InChiKey: FNEJVILWEFBXJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  89.21
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  7-hydroxy-5-(2-morpholinoethoxy)-2-oxo-4-propyl-2H-chromene-8-carbaldehyde 在 叠氮磷酸二苯酯 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 5-(2-morpholin-4-ylethoxy)-8-nitro-4-propyl-7H-pyrano[2,3-e]indol-2-one
  参考文献：
  名称：

  Synthetic Calanolides with Bactericidal Activity against Replicating and Nonreplicating Mycobacterium tuberculosis

  摘要：

  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.

  DOI：

  10.1021/jm4019228
• 作为产物：
  描述：

  5,7-二羟基-4-丙基香豆素 在 三苯基膦 、 偶氮二甲酸二乙酯 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 7-hydroxy-5-(2-morpholinoethoxy)-2-oxo-4-propyl-2H-chromene-8-carbaldehyde
  参考文献：
  名称：

  Synthetic Calanolides with Bactericidal Activity against Replicating and Nonreplicating Mycobacterium tuberculosis

  摘要：

  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.

  DOI：

  10.1021/jm4019228

文献信息

• Modified calanolides incorporated with furan-2-nitro mimics against Mycobacterium tuberculosis
  作者：Zijie Liu、Xiaoyong Guo、Gang Liu

  DOI：10.1016/j.bmcl.2015.01.046

  日期：2015.3

  (+)-Calanolide A was identified as an active agent against both HIV-1 and Mycobacterium tuberculosis (Mtb). We modified Ring D of calanolide compounds with furan-2-nitro mimics and obtained 15 compounds. After in vitro tests, two compounds were shown to be active against replicating (R) Mtb, but not against non-replicating (NR) Mtb. Further optimization for potent candidates against both R Mtb and NR Mtb will result from this research. (C) 2015 Elsevier Ltd. All rights reserved.

  (+)-川芎嗪A被鉴定为对抗HIV-1和结核分枝杆菌（Mtb）的活性剂。我们对川芎嗪类化合物的环D进行修饰，采用了呋喃-2-硝基的模拟物，获得了15种化合物。经过体外测试，其中两种化合物对复制型（R）结核分枝杆菌表现出活性，但对非复制型（NR）结核分枝杆菌无活性。本研究为进一步优化针对R型和NR型结核分枝杆菌的高效候选药物奠定了基础。（C）2015金佰利有限公司版权所有。