(Z)-2-(3-(tert-butyldimethylsilyloxy)propenyl)phenol | 185995-96-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Z)-2-(3-(tert-butyldimethylsilyloxy)propenyl)phenol
• 英文别名: 2-[(Z)-3-[tert-butyl(dimethyl)silyl]oxyprop-1-enyl]phenol
• CAS: 185995-96-4
• 化学式: C₁₅H₂₄O₂Si
• 分子量: 264.44
• InChiKey: DABLIYCOMTWUDM-NTMALXAHSA-N

物化性质

• 沸点：
  347.0±30.0 °C(Predicted)
• 密度：
  0.979±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.43
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (Z)-2-(3-(tert-butyldimethylsilyloxy)propenyl)phenol 在 4-二甲氨基吡啶 、 sodium chlorite 、 TEA 、 水 、 双氧水 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 sodium phosphate 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 溶剂黄146 、 乙腈 为溶剂， 反应 9.0h， 生成 [2-[(Z)-3-(diethylamino)-3-oxoprop-1-enyl]phenyl] acetate
  参考文献：
  名称：

  基于香豆素的前药。第3部分：结构对胺的酯酶敏感性前药释放动力学的影响。

  摘要：

  为了研究对香豆素基酯酶敏感的前药系统的释放动力学的结构影响，合成了酯“触发”部分和胺“药物”部分具有不同结构特征的两个系列化合物。在猪肝酯酶存在下，这九种模型前药的半衰期为约2分钟至190分钟。酰基的空间体积似乎对酯酶触发的胺从模型前药中释放的半衰期影响很小。内酯化的速率取决于胺部分的空间和电子性质。

  DOI：

  10.1016/s0968-0896(98)00014-5
• 作为产物：
  描述：

  香豆素 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 作用下， 反应 14.25h， 生成 (Z)-2-(3-(tert-butyldimethylsilyloxy)propenyl)phenol
  参考文献：
  名称：

  Design, synthesis, and bioavailability evaluation of coumarin-based prodrug of meptazinol

  摘要：

  Based on the known coumarin-based prodrug system, a new meptazinol (Z)-3-[2-(propionyloxy) phenyl]-2-propenoic ester (3) was designed and synthesized as prodrug to minimize the first-pass effect of meptazinol (1) and improve the oral bioavailability. The prodrug (3) showed a 4-fold increase in oral bioavailability over the parent drug meptazinol in rats. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.016

文献信息

• Synthesis and Evaluation of Novel Coumarin-Based Esterase-Sensitive Cyclic Prodrugs of Peptidomimetic RGD Analogs with Improved Membrane Permeability.
  作者：Binghe WANG、Wei WANG、Gian P. CAMENISCH、Jennifer ELMO、Huijuan ZHANG、Ronald T. BORCHARDT

  DOI：10.1248/cpb.47.90

  日期：——

  Earlier, we reported the development of a coumarin-based prodrug system that could be used for the preparation of cyclic prodrugs of opioid peptides. These cyclic prodrugs exhibited excellent membrane permeability characteristics. Therefore, it was of interest to determine the effects of this prodrug strategy on the membrane permeabilities of peptidomimetics which also have low membrane permeabilities. For this study, we have chosen two RGD (Arg-Gly-Asp) peptidomimetics, which have the potentials to be developed clinically as orally active antithrombotic agents. However, the clinical development of oral dosage forms of these RGD analogs has been hindered by their low intestinal mucosal permeability. Therefore, we have synthesized the corresponding coumarin-based cyclic prodrugs of these RGD peptidomimetics, which have the two most polar functional groups, a carboxyl and an amino group, masked as an ester and an amide, respectively. These cyclic prodrugs were shown to have higher membrane interaction potentials, as estimated by their partitioning between aqueous buffer and an immobilized artificial membrane, than the corresponding RGD analogs suggesting that they should exhibit good membrane permeation characteristics. Subsequently, in a separate study these cyclic prodrugs were shown to be 5 to 6-fold more able to permeate monolayers of Caco-2 cells, an in vitro cell culture model of the intestinal mucosa barrier, than the corresponding RGD peptidomimetics.

  早些时候，我们报道了香豆素原药体系的开发，该体系可用于制备阿片肽的环状原药。这些环状原药具有出色的膜渗透特性。因此，我们有兴趣确定这种原药策略对膜渗透性较低的拟肽类药物膜渗透性的影响。在这项研究中，我们选择了两种 RGD（Arg-Gly-Asp）拟肽物，它们具有作为口服活性抗血栓药物进行临床开发的潜力。然而，由于这些 RGD 类似物的肠粘膜渗透性较低，其口服剂型的临床开发一直受到阻碍。因此，我们合成了这些 RGD 肽拟类似物的相应香豆素基环状原药，其两个极性最强的官能团（羧基和氨基）分别被掩蔽为酯和酰胺。根据这些环状原药在水缓冲液和固定人工膜之间的分配估计，它们比相应的 RGD 类似物具有更高的膜相互作用电位，这表明它们应该具有良好的膜渗透特性。随后，在另一项研究中，这些环状原药渗透 Caco-2 细胞单层（一种肠粘膜屏障的体外细胞培养模型）的能力比相应的 RGD 肽模拟物强 5 到 6 倍。
• Chemical feasibility studies of a potential coumarin-based prodrug system
  作者：Binghe Wang、Huijuan Zhang、Wei Wang

  DOI：10.1016/0960-894x(96)00147-3

  日期：1996.4
• Design, synthesis, and bioavailability evaluation of coumarin-based prodrug of meptazinol
  作者：Qiong Xie、Xiaolin Wang、Xinghai Wang、Zhiqiang Jiang、Zhuibai Qiu

  DOI：10.1016/j.bmcl.2005.08.016

  日期：2005.11

  Based on the known coumarin-based prodrug system, a new meptazinol (Z)-3-[2-(propionyloxy) phenyl]-2-propenoic ester (3) was designed and synthesized as prodrug to minimize the first-pass effect of meptazinol (1) and improve the oral bioavailability. The prodrug (3) showed a 4-fold increase in oral bioavailability over the parent drug meptazinol in rats. (c) 2005 Elsevier Ltd. All rights reserved.
• Coumarin-based prodrugs. Part 3: Structural effects on the release kinetics of esterase-sensitive prodrugs of amines 1 1Part of this work was performed at the University of Oklahoma Health Sciences Center, College of Pharmacy.
  作者：Binghe Wang、Huijuan Zhang、Ailian Zheng、Wei Wang

  DOI：10.1016/s0968-0896(98)00014-5

  日期：1998.4

  structural effects on the release kinetics of a coumarin-based esterase-sensitive prodrug system, two series of compounds with varying structural features of the ester 'trigger' part and the amine 'drug' part were synthesized. The half-lives of the nine model prodrugs in the presence of porcine liver esterase ranged from about 2 min to 190 min. The steric bulkiness of the acyl group seems to have only a

  为了研究对香豆素基酯酶敏感的前药系统的释放动力学的结构影响，合成了酯“触发”部分和胺“药物”部分具有不同结构特征的两个系列化合物。在猪肝酯酶存在下，这九种模型前药的半衰期为约2分钟至190分钟。酰基的空间体积似乎对酯酶触发的胺从模型前药中释放的半衰期影响很小。内酯化的速率取决于胺部分的空间和电子性质。