2-(benzo[1,3]dioxol-5-yl)-1-(4-benzyloxyphenyl)-4-oxobutyric acid methyl ester | 169804-39-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2-(benzo[1,3]dioxol-5-yl)-1-(4-benzyloxyphenyl)-4-oxobutyric acid methyl ester
• 英文别名: 2-(1,3-benzodioxol-5-yl)-1-(4-benzyloxyphenyl)-4-oxobutyric acid methyl ester；Methyl 2-(1,3-benzodioxol-5-yl)-4-oxo-4-(4-phenylmethoxyphenyl)butanoate
• CAS: 169804-39-1
• 化学式: C₂₅H₂₂O₆
• 分子量: 418.446
• InChiKey: YCUQLHVMWMERNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(benzo[1,3]dioxol-5-yl)-1-(4-benzyloxyphenyl)-4-oxobutyric acid methyl ester 在 palladium on activated charcoal 氨 、 氢气 、 碘 、 sodium methylate 作用下， 以 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 29.0h， 生成 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5-(4-hydroxy-3-iodo-phenyl)-4-(3,4,5-trimethoxy-benzyl)-5H-furan-2-one
  参考文献：
  名称：

  Synthesis, in vitro pharmacology and biodistribution studies of new PD 156707-derived ETA receptor radioligands

  摘要：

  It is assumed that the regulation of cardiac endothelin (ET) receptor density is abnormal in heart diseases. From that perspective, an ET receptor radioligand is needed to assess ET receptor density in vivo. The nonpeptidyl ETA receptor antagonist PD 169390 was labelled with radioiodine to give a putative radioligand for SPECT. Labelling with [I-125]iodide and [I-123]iodide was accomplished with good to excellent radiochemical yields. The affinities of the nonradioactive reference and those of selected precursor compounds for ETA receptors were determined, using [I-125]iodine labelled endothelin-1 with mouse ventricular membranes. All employed substances exhibited potent in vitro pharmacological characteristics with K-i values comparable to that of the lead compound PD 156707. Biodistribution studies and scintigraphic imaging experiments in mice, however, showed no significant uptake of the [I-123] derivative in the heart. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.039
• 作为产物：
  描述：

  (E)-3-(1,3-benzodioxol-5-yl)-1-(4-phenylmethoxyphenyl)prop-2-en-1-one 在 对甲苯磺酸 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 乙二醇乙醚 、 水 为溶剂， 反应 0.5h， 生成 2-(benzo[1,3]dioxol-5-yl)-1-(4-benzyloxyphenyl)-4-oxobutyric acid methyl ester
  参考文献：
  名称：

  一系列口服活性γ-羟基丁烯内酯内皮素拮抗剂的构效关系。

  摘要：

  设计有效的和选择性的内皮素-1（ET-1）及其相关异肽类非肽拮抗剂是确定ET在人类疾病中的作用的重要工具。在本报告中，我们将描述详细的结构-活性关系（SAR）研究，该研究导致发现了一系列有效的丁烯内酯ETA选择拮抗剂。从微摩尔筛选产物PD012527开始，使用Topliss决策树分析导致发现纳摩尔ET（A）选择性拮抗剂PD155080。丁烯内酯环周围的进一步结构修饰直接导致了亚纳摩尔ETA选择性拮抗剂PD156707，IC50 = 0.3（ET（A））和780 nM（ET（B））。该系列化合物表现出以PD156707为例的功能活性。该衍生物抑制ETA受体介导的花生四烯酸从兔肾动脉血管平滑肌细胞中释放，IC50 = 1.1 nM，并且还抑制ET-1诱导的兔股动脉环收缩（ETA介导），pA2 = 7.6。PD156707还显示出体内功能活性，该活性功能抑制了大鼠以剂量依赖方式外源给予ET-1引

  DOI：

  10.1021/jm9606507

文献信息

• PET-compatible endothelin receptor radioligands: Synthesis and first in vitro and in vivo studies
  作者：Carsten Höltke、Marilyn P. Law、Stefan Wagner、Klaus Kopka、Andreas Faust、Hans-Jörg Breyholz、Otmar Schober、Christoph Bremer、Burkhard Riemann、Michael Schäfers

  DOI：10.1016/j.bmc.2009.08.058

  日期：2009.10

  The expression and function of endothelin (ET) receptors is abnormal in cardiovascular diseases, tumor progression, and tumor metastasis. In this study, we prepared two [F-18]-fluorinated derivatives of the non-peptide ETA receptor antagonist PD 156707 and evaluated their ET receptor binding potencies. Ex vivo as well as in vivo biodistribution studies in mice were performed, as well as the metabolism of the radiotracer, which was examined by metabolite analysis in mice and rats. All tested derivatives of PD 156707 exhibited potent in vitro pharmacological characteristics with K-i values comparable to that of the lead compound. The biodistribution studies showed a high accumulation of the tracer in bile and intestine. In vivo we were able to show that the visualization of the heart as a major target organ with high ETAR expression is possible. (C) 2009 Elsevier Ltd. All rights reserved.