4-methoxy-5-(5-ethyl-1H-pyrrol-2-ylmethylidene)-1,5-dihydropyrrol-2-one | 289058-28-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-methoxy-5-(5-ethyl-1H-pyrrol-2-ylmethylidene)-1,5-dihydropyrrol-2-one
• 英文别名: 5-[(5-ethyl-1H-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-one
• CAS: 289058-28-2
• 化学式: C₁₂H₁₄N₂O₂
• 分子量: 218.255
• InChiKey: GXKBJPISIZIVGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.58
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.12
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-methoxy-5-(5-ethyl-1H-pyrrol-2-ylmethylidene)-1,5-dihydropyrrol-2-one 在 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 4-methoxy-5-[(5-ethyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi-1H-pyrrole
  参考文献：
  名称：

  Influence of the A-Ring on the Proton Affinity and Anticancer Properties of the Prodigiosins

  摘要：

  Prodigiosin (Prod, 1) is the parent member of a class of polypyrrole natural products that exhibit promising immunosuppressive and anticancer activities. They are known to act as H+/ Cl- symporters possibly through electrostatic binding to Cl- that facilitates proton-coupled transmembrane transport of halides. This activity has been ascribed to their promotion of apoptosis by acidification of the intracellular pH (pHi). Since the protonated pyrromethene chromophore of Prod (1) is expected to play a critical role in pHi regulation, and the A-pyrrole ring is known to be important for anticancer activity, we prepared several Prod analogues with various A-ring systems to determine their proton affinity in 1: 1 (v/v) acetonitrile (MeCN)/ H2O and anticancer properties against HL-60 cancer cells. Our studies show that the A-ring strongly influences the proton affinity of the pyrromethene entity. Replacement of the C-2 methoxy group in 2,4-dimethoxy-pyrromethene 3 (apparent pK(a) = 4.95) with the A-pyrrole ring to generate the Prod analogue 5 raised the apparent pK(a) to 7.54 (increase by 2.59 pK units) and caused a 76 nm red shift in the UV-vis absorbance of the protonated species (AH(+)). The A-pyrrole NH atom plays an important role in stabilization of AH(+), as its replacement with 0 or S atoms decreases the apparent pK(a) by 0.79 and 1.07 pK units, respectively. A 4-substituted phenyl series of Prod analogues 8-14 exhibited a linear correlation with the Hammett sigma(p) values. Within the phenyl series, two Prod analogues were found to inhibit colony formation of HL-60 cancer cells, although the inhibition did not correlate with the proton affinity of the pyrromethene entity. The implications of these findings with regard to the anticancer activities of the prodigiosins are discussed.

  DOI：

  10.1021/tx025507x
• 作为产物：
  描述：

  2-乙基吡咯 在 sodium hydroxide 、 三氯氧磷 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 4-methoxy-5-(5-ethyl-1H-pyrrol-2-ylmethylidene)-1,5-dihydropyrrol-2-one
  参考文献：
  名称：

  Influence of the A-Ring on the Proton Affinity and Anticancer Properties of the Prodigiosins

  摘要：

  Prodigiosin (Prod, 1) is the parent member of a class of polypyrrole natural products that exhibit promising immunosuppressive and anticancer activities. They are known to act as H+/ Cl- symporters possibly through electrostatic binding to Cl- that facilitates proton-coupled transmembrane transport of halides. This activity has been ascribed to their promotion of apoptosis by acidification of the intracellular pH (pHi). Since the protonated pyrromethene chromophore of Prod (1) is expected to play a critical role in pHi regulation, and the A-pyrrole ring is known to be important for anticancer activity, we prepared several Prod analogues with various A-ring systems to determine their proton affinity in 1: 1 (v/v) acetonitrile (MeCN)/ H2O and anticancer properties against HL-60 cancer cells. Our studies show that the A-ring strongly influences the proton affinity of the pyrromethene entity. Replacement of the C-2 methoxy group in 2,4-dimethoxy-pyrromethene 3 (apparent pK(a) = 4.95) with the A-pyrrole ring to generate the Prod analogue 5 raised the apparent pK(a) to 7.54 (increase by 2.59 pK units) and caused a 76 nm red shift in the UV-vis absorbance of the protonated species (AH(+)). The A-pyrrole NH atom plays an important role in stabilization of AH(+), as its replacement with 0 or S atoms decreases the apparent pK(a) by 0.79 and 1.07 pK units, respectively. A 4-substituted phenyl series of Prod analogues 8-14 exhibited a linear correlation with the Hammett sigma(p) values. Within the phenyl series, two Prod analogues were found to inhibit colony formation of HL-60 cancer cells, although the inhibition did not correlate with the proton affinity of the pyrromethene entity. The implications of these findings with regard to the anticancer activities of the prodigiosins are discussed.

  DOI：

  10.1021/tx025507x

文献信息

• Design, synthesis, molecular modeling, and bioactivity evaluation of 1,10-phenanthroline and prodigiosin (Ps) derivatives and their Copper(I) complexes against mTOR and HDAC enzymes as highly potent and effective new anticancer therapeutic drugs
  作者：M. Mustafa Cetin、Wenjing Peng、Daniel Unruh、Michael F. Mayer、Yehia Mechref、Kemal Yelekci

  DOI：10.3389/fphar.2022.980479

  日期：——

  in the development of breast cancer brain metastasis. Therefore, it is vital to develop some new drugs and conduct studies toward the inhibition of these enzymes that might be a possible solution to treat breast cancer brain metastasis. In this study, a series of 1,10-phenanthroline and Prodigiosin derivatives consisting of their copper(I) complexes have been synthesized and characterized. Their biological

  乳腺癌是脑转移概率第二高的癌症，由于缺乏有效的治疗方法，一直是乳腺癌研究的主要问题之一。开发一种有效的抗乳腺癌脑转移药物和寻找在有效治疗中起作用的分子机制的需求正在逐渐增加。然而，目前还没有针对乳腺癌，特别是对于脑转移高危患者的有效抗癌治疗药物或治疗方法。已知mTOR和HDAC酶在乳腺癌脑转移的发展中起重要作用。因此，开发一些新药并进行研究以抑制这些酶可能是治疗乳腺癌脑转移的可能解决方案至关重要。在这项研究中，合成并表征了一系列由其铜 (I) 配合物组成的 1,10-菲咯啉和灵菌红素衍生物。测试了它们的生物活性体外在六种不同的细胞系（包括正常细胞系）上。为了获得对实验数据的额外平行验证，一些计算机对 mTOR 和 HDAC1 酶进行了建模研究，这些酶是非常重要的药物靶点，以发现治疗乳腺癌和相关脑转移疾病的新型有效药物。
• Influence of the <b>A</b>-Ring on the Proton Affinity and Anticancer Properties of the Prodigiosins
  作者：Matt S. Melvin、John T. Tomlinson、Gyungse Park、Cynthia S. Day、Gilda R. Saluta、Gregory L. Kucera、Richard A. Manderville

  DOI：10.1021/tx025507x

  日期：2002.5.1

  Prodigiosin (Prod, 1) is the parent member of a class of polypyrrole natural products that exhibit promising immunosuppressive and anticancer activities. They are known to act as H+/ Cl- symporters possibly through electrostatic binding to Cl- that facilitates proton-coupled transmembrane transport of halides. This activity has been ascribed to their promotion of apoptosis by acidification of the intracellular pH (pHi). Since the protonated pyrromethene chromophore of Prod (1) is expected to play a critical role in pHi regulation, and the A-pyrrole ring is known to be important for anticancer activity, we prepared several Prod analogues with various A-ring systems to determine their proton affinity in 1: 1 (v/v) acetonitrile (MeCN)/ H2O and anticancer properties against HL-60 cancer cells. Our studies show that the A-ring strongly influences the proton affinity of the pyrromethene entity. Replacement of the C-2 methoxy group in 2,4-dimethoxy-pyrromethene 3 (apparent pK(a) = 4.95) with the A-pyrrole ring to generate the Prod analogue 5 raised the apparent pK(a) to 7.54 (increase by 2.59 pK units) and caused a 76 nm red shift in the UV-vis absorbance of the protonated species (AH(+)). The A-pyrrole NH atom plays an important role in stabilization of AH(+), as its replacement with 0 or S atoms decreases the apparent pK(a) by 0.79 and 1.07 pK units, respectively. A 4-substituted phenyl series of Prod analogues 8-14 exhibited a linear correlation with the Hammett sigma(p) values. Within the phenyl series, two Prod analogues were found to inhibit colony formation of HL-60 cancer cells, although the inhibition did not correlate with the proton affinity of the pyrromethene entity. The implications of these findings with regard to the anticancer activities of the prodigiosins are discussed.