PD 169390 | 313222-88-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: PD 169390
• 英文别名: 3-(1,3-Benzodioxol-5-yl)-5-hydroxy-5-(4-hydroxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]furan-2-one
• CAS: 313222-88-7
• 化学式: C₂₇H₂₄O₉
• 分子量: 492.482
• InChiKey: OEIKFCIWOVHZSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  PD 169390 在 sodium hydroxide sodium iodide 、 K₂HPO₄ buffer 、 chloroamine-T 作用下， 以 甲醇 为溶剂， 反应 0.08h， 生成 [123I]3-(benzo[1,3]dioxol-5-yl)-5-hydroxy-5-(4-hydroxy-3-iodophenyl)-4-(3,4,5-trimethoxybenzyl)-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：

  2-(benzo[1,3]dioxol-5-yl)-1-(4-benzyloxyphenyl)-4-oxobutyric acid methyl ester 在 palladium on activated charcoal 氢气 、 sodium methylate 作用下， 以 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 28.0h， 生成 PD 169390
  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

文献信息

• A Transgenic Strategy for Analysis of the Function of the Endothelin-B-Receptor
  作者：Alan Bagnall、David Webb、Yuri Kotelevtsev

  DOI：10.1097/00005344-200036001-00029

  日期：——

  Summary:  Knockout (KO) models have provided important insights into the function of many receptors and signalling molecules. However, analysis of endothelin (ET) receptor knockouts has been complicated by the development of lethal phenotypes. In this paper, we present our strategy for examining endothelin-B- (ETB) receptor function in the context of other strategies for rescuing the lethal phenotype of ETB knockout mice.

  摘要：基因敲除（KO）模型为了解许多受体和信号分子的功能提供了重要线索。然而，对内皮素（ET）受体基因敲除的分析因出现致死表型而变得复杂。在本文中，我们结合其他挽救 ETB 基因敲除小鼠致死表型的策略，介绍了我们研究内皮素-B（ETB）受体功能的策略。
• Synthesis, in vitro pharmacology and biodistribution studies of new PD 156707-derived ETA receptor radioligands
  作者：Carsten Höltke、Marilyn P. Law、Stefan Wagner、Hans-Jörg Breyholz、Klaus Kopka、Christoph Bremer、Bodo Levkau、Otmar Schober、Michael Schäfers

  DOI：10.1016/j.bmc.2005.10.039

  日期：2006.3

  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.