2-hydroxymethyl-1,4-benzoxathiane | 35143-11-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-hydroxymethyl-1,4-benzoxathiane
• 英文别名: 2-Hydroxymethyl-1,4-benzoxathian；(RS)-2,3-dihydro-1,4-benzoxathiin-2-methanol；2,3-Dihydro-1,4-benzoxathiin-2-ylmethanol
• CAS: 35143-11-4
• 化学式: C₉H₁₀O₂S
• mdl: MFCD15209552
• 分子量: 182.243
• InChiKey: CHVOMUACRIMGII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  54.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-hydroxymethyl-1,4-benzoxathiane 、 腺嘌呤 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以30%的产率得到(RS)-6-amino-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine
  参考文献：
  名称：

  Synthesis and anticancer activity of (RS)-9-(2,3-dihydro-1,4-benzoxaheteroin-2-ylmethyl)-9H-purines

  摘要：

  Herein are reported the synthesis and anticancer activity against the human breast cancer cell line MCF-7 of a series of substituted (RS)-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine derivatives and (RS)-9-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-9H-purine derivatives. When the Mitsunobu reaction was carried out between (RS)-2,3-dihydro-1,4-benzoxathiin-3-methanol and the heterocyclic bases 6-chloro-, 2,6-dichloro, and 6-bromo-purines under microwave-assisted conditions, a formal 1,4-sulfur migration takes place through two consecutive oxyranium and episulfonium rings, giving rise to the corresponding (RS)-9-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-9H-purine derivatives, previously reported by us. The most active compound (RS)-2,6-dichloro-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine shows an IC50 = 2.75 +/- 0.02 mu M. When the cancerous cells were treated with this compound, a significant increase of apoptotic cells (70.08 +/- 0.33%) was obtained in relation to the control ones. The induction of the G(2)/M cell cycle arrest and apoptosis by the three most active compounds is associated with increased phosphorylation of eIF2 alpha in human breast cancer cells. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.046
• 作为产物：
  描述：

  2-羟基苯硫酚 、 2,3-二溴丙酸乙酯 在 三乙胺 、 lithium aluminium tetrahydride 作用下， 以 水 、 乙腈 、 四氢呋喃 为溶剂， 生成 2-hydroxymethyl-1,4-benzoxathiane 、 (2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol
  参考文献：
  名称：

  Benzamide Derivatives Targeting the Cell Division Protein FtsZ: Modifications of the Linker and the Benzodioxane Scaffold and Their Effects on Antimicrobial Activity

  摘要：

  细丝状温敏Z（FtsZ）是一种原核蛋白，在细菌细胞分裂过程中起着重要作用。它在革兰氏阳性和革兰氏阴性菌株中广泛保守和表达。在过去的十年中，几个研究小组已经指出了一些能够靶向金黄色葡萄球菌、枯草杆菌和其他革兰氏阳性菌株中的FtsZ的分子，具有亚微摩尔最低抑菌浓度（MICs）。相反，到目前为止还没有发现对革兰氏阴性菌有效的有希望的衍生物。在这里，我们报告了一类苯甲酰胺化合物的结果，这些化合物在金黄色葡萄球菌和大肠杆菌的FtsZ上显示出可比较的抑制活性，尽管它们被大肠杆菌外排泵AcrAB的底物，从而影响了抗菌活性。这些令人惊讶的结果证实了一种单一分子如何可以同时靶向两种物种，同时保持强大的抗

  DOI：

  10.3390/antibiotics9040160

文献信息

• Synthesis and anticancer activity of (RS)-9-(2,3-dihydro-1,4-benzoxaheteroin-2-ylmethyl)-9H-purines
  作者：Ana Conejo-García、M. Eugenia García-Rubiño、Juan A. Marchal、M. Carmen Núñez、Alberto Ramírez、Sandro Cimino、M. Ángel García、Antonia Aránega、Miguel A. Gallo、Joaquín M. Campos

  DOI：10.1016/j.ejmech.2011.05.046

  日期：2011.9

  Herein are reported the synthesis and anticancer activity against the human breast cancer cell line MCF-7 of a series of substituted (RS)-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine derivatives and (RS)-9-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-9H-purine derivatives. When the Mitsunobu reaction was carried out between (RS)-2,3-dihydro-1,4-benzoxathiin-3-methanol and the heterocyclic bases 6-chloro-, 2,6-dichloro, and 6-bromo-purines under microwave-assisted conditions, a formal 1,4-sulfur migration takes place through two consecutive oxyranium and episulfonium rings, giving rise to the corresponding (RS)-9-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-9H-purine derivatives, previously reported by us. The most active compound (RS)-2,6-dichloro-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine shows an IC50 = 2.75 +/- 0.02 mu M. When the cancerous cells were treated with this compound, a significant increase of apoptotic cells (70.08 +/- 0.33%) was obtained in relation to the control ones. The induction of the G(2)/M cell cycle arrest and apoptosis by the three most active compounds is associated with increased phosphorylation of eIF2 alpha in human breast cancer cells. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Benzamide Derivatives Targeting the Cell Division Protein FtsZ: Modifications of the Linker and the Benzodioxane Scaffold and Their Effects on Antimicrobial Activity
  作者：Valentina Straniero、Lorenzo Suigo、Andrea Casiraghi、Victor Sebastián-Pérez、Martina Hrast、Carlo Zanotto、Irena Zdovc、Carlo De Giuli Morghen、Antonia Radaelli、Ermanno Valoti

  DOI：10.3390/antibiotics9040160

  日期：——

  Filamentous temperature-sensitive Z (FtsZ) is a prokaryotic protein with an essential role in the bacterial cell division process. It is widely conserved and expressed in both Gram-positive and Gram-negative strains. In the last decade, several research groups have pointed out molecules able to target FtsZ in Staphylococcus aureus, Bacillus subtilis and other Gram-positive strains, with sub-micromolar Minimum Inhibitory Concentrations (MICs). Conversely, no promising derivatives active on Gram-negatives have been found up to now. Here, we report our results on a class of benzamide compounds, which showed comparable inhibitory activities on both S. aureus and Escherichia coli FtsZ, even though they proved to be substrates of E. coli efflux pump AcrAB, thus affecting the antimicrobial activity. These surprising results confirmed how a single molecule can target both species while maintaining potent antimicrobial activity. A further computational study helped us decipher the structural features necessary for broad spectrum activity and assess the drug-like profile and the on-target activity of this family of compounds.

  细丝状温敏Z（FtsZ）是一种原核蛋白，在细菌细胞分裂过程中起着重要作用。它在革兰氏阳性和革兰氏阴性菌株中广泛保守和表达。在过去的十年中，几个研究小组已经指出了一些能够靶向金黄色葡萄球菌、枯草杆菌和其他革兰氏阳性菌株中的FtsZ的分子，具有亚微摩尔最低抑菌浓度（MICs）。相反，到目前为止还没有发现对革兰氏阴性菌有效的有希望的衍生物。在这里，我们报告了一类苯甲酰胺化合物的结果，这些化合物在金黄色葡萄球菌和大肠杆菌的FtsZ上显示出可比较的抑制活性，尽管它们被大肠杆菌外排泵AcrAB的底物，从而影响了抗菌活性。这些令人惊讶的结果证实了一种单一分子如何可以同时靶向两种物种，同时保持强大的抗