4-benzyloxyphenoxyethyl tetrahydro-2H-pyran-2-yl ether | 205381-75-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-benzyloxyphenoxyethyl tetrahydro-2H-pyran-2-yl ether
• 英文别名: 2-[2-(4-Phenylmethoxyphenoxy)ethoxy]oxane
• CAS: 205381-75-5
• 化学式: C₂₀H₂₄O₄
• 分子量: 328.408
• InChiKey: WQNKRRHQPXDJNT-UHFFFAOYSA-N

物化性质

• 沸点：
  484.2±45.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-benzyloxyphenoxyethyl tetrahydro-2H-pyran-2-yl ether 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 以100%的产率得到p-(2-hydroxyethoxy)benzyloxybenzene
  参考文献：
  名称：

  一类新型双官能四亚苯基冠醚的合成

  摘要：

  已经制备了三种新的取代四亚苯基冠醚。双（5-碳甲氧基-1,3-亚苯基）-双（对-亚苯基）-(3x + 6)-冠-x，其中 x = 12、16 和 20 (11b-11d) 通过 [1 + 1] 3,5-双[ω-氯（低聚亚乙氧基）]苯甲酸甲酯（13b-3d）与3,5-双[ω-（对羟基苯氧基）（低聚亚乙氧基）]苯甲酸甲酯（16b-6d）环化K2CO3 作为碱和四丁基碘化铵作为二甲基甲酰胺 (DMF) 中的相转移剂。相应的 30 元 (x = 8) 大环 11a 不能通过这种方法制成；仅分离出消除产物 3,5-双（乙烯基氧基）苯甲酸 (19)。16a-16d 分别通过对苄氧基苯酚 (14) 与 13a-13d 的烷基化反应制备，然后用 Pd/C 作为催化剂进行氢解。

  DOI：

  10.1139/v98-188
• 作为产物：
  描述：

  2-(2-溴乙氧基)四氢吡喃 、 4-苄氧基苯酚 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 0.08h， 以96%的产率得到4-benzyloxyphenoxyethyl tetrahydro-2H-pyran-2-yl ether
  参考文献：
  名称：

  芳氧基乙基硫氰酸盐是克氏锥虫和弓形虫的有效生长抑制剂

  摘要：

  作为我们旨在寻找针对寄生虫病的新型安全化疗药物的项目的一部分，设计、合成了几种结构上与抗寄生虫药物 WC-9（4-苯氧基苯氧基乙基硫氰酸酯）相关的化合物，这些化合物在末端苯环上进行了修饰，并被评估为针对克氏锥虫（恰加斯病的病原体）和弓形虫（引起弓形体病的寄生虫）的生长抑制剂。大多数合成类似物表现出相似的抗寄生虫活性，并且比我们的先导 WC-9 稍强一些。例如，两种三氟甲基化衍生物针对细胞内克氏弓形虫表现出 10.0 和 9.2 μM的 ED 50值，而针对弓形虫速殖子表现出有效的作用（针对弓形虫的 ED 50值为 1.6 和 1.9 μM ）。此外，末端芳基位于带有硫氰酸酯基团的烷基链间位的 WC-9 类似物在非常低的微摩尔范围内对克氏弓形虫和刚地弓形虫均表现出有效的抑制作用。表明对苯基取代模式对于生物活性来说不是必需的。

  DOI：

  10.1002/cmdc.201500100

文献信息

• Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents
  作者：Pablo D. Elicio、María N. Chao、Melina Galizzi、Catherine Li、Sergio H. Szajnman、Roberto Docampo、Silvia N.J. Moreno、Juan B. Rodriguez

  DOI：10.1016/j.ejmech.2013.09.009

  日期：2013.11

  As a part of our project pointed at the search of new safe chemotherapeutic and chemoprophylactic agents against parasitic diseases, several compounds structurally related to 4-phenoxyphenoxyethyl thiocyanate (WC-9), which were modified at the terminal aromatic ring, were designed, synthesized and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible of American

  作为我们项目的一部分，旨在寻找针对寄生虫病的新型安全化学治疗剂和化学预防剂，我们设计、合成了几种与 4-苯氧基苯氧基乙基硫氰酸酯 ( WC - 9 )结构相关的化合物，这些化合物在末端芳环上进行了修饰。被评估为抗克氏锥虫的抗增殖剂，克氏锥虫是导致美洲锥虫病（南美锥虫病）和弓形虫，弓形虫病的病原体的寄生虫。大多数合成类似物表现出类似的抗寄生虫活性，比参考化合物WC - 9更有效。例如，硝基衍生物13显示5.2 μM的 ED 50值。有趣的是，WC - 9的区域异构体化合物36显示出与WC - 9相似的抑制作用，表明对苯基取代模式不一定是生物活性所必需的。针对弓形虫的生物学评价也非常有希望。该ED 50个对应于值13，36和37是在对的速殖子的非常低的微摩尔水平弓形虫。
• Structure−Activity Relationship of New Growth Inhibitors of <i>Trypanosoma</i> <i>cruzi</i>
  作者：Güendalina M. Cinque、Sergio H. Szajnman、Li Zhong、Roberto Docampo、Andrea J. Schvartzapel、Juan B. Rodriguez、Eduardo G. Gros

  DOI：10.1021/jm970860z

  日期：1998.4.1

  Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety replacing selected aromatic protons by different groups via electrophilic aromatic substitution reactions as well as introducing a sulfur atom at the polar extreme. Of the designed compounds, sulfur-containing derivatives were shown to be potent antireplicative agents against T. cruzi. Among these drugs, 4-phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC50 of 2.2 mu M. Under the same assay conditions, this drug was much more active than Nifurtimox, one of the drugs currently in clinical use to control this disease. This thiocyanate derivative was also a very active inhibitor against the intracellular form of the parasite at the nanomolar level. Other sulfur derivatives prepared also exhibited very potent antiproliferative action against T. cruzi. The presence of a sulfur atom at the polar extreme for this family of compounds seems to be very important for biological action because this atom was always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate presents very good prospective not only as a lead drug but also as a potential chemotherapeutic agent.
• Synthesis and Structure–Activity Relationships of Varied Ether Linker Analogues of the Antitubercular Drug (6<i>S</i>)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazine (PA-824)
  作者：Andrew M. Thompson、Hamish S. Sutherland、Brian D. Palmer、Iveta Kmentova、Adrian Blaser、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、William A. Denny

  DOI：10.1021/jm200377r

  日期：2011.10.13

  New analogues of antitubercular drug PA-824 were synthesized, featuring alternative side chain ether linkers of varying size and flexibility, seeking drug candidates with enhanced metabolic stability and high efficacy. Both alpha-methyl substitution and removal of the benzylic methylene were broadly tolerated in vitro, with a biaryl example of the latter class exhibiting an 8-fold better efficacy than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection and negligible fragmentation to an alcohol metabolite in liver microsomes. Extended linkers (notably propenyloxy, propynyloxy, and pentynyloxy) provided greater potencies against replicating M. tb (monoaryl analogues), with propynyl ethers being most effective under anaerobic (nonreplicating) conditions (mono/biaryl analogues). For benzyloxybenzyl and biaryl derivatives, aerobic activity was maximal with the original (OCH2) linker. One propynyloxy-linked compound displayed an 89-fold higher efficacy than the parent drug in the acute model, and it was slightly superior to antitubercular drug OPC-67683 in a chronic infection model.
• WO2023/102477
  申请人：——

  公开号：——

  公开（公告）日：——
• Aryloxyethyl Thiocyanates Are Potent Growth Inhibitors of<i>Trypanosoma cruzi</i>and<i>Toxoplasma gondii</i>
  作者：María N. Chao、Carolina Exeni Matiuzzi、Melissa Storey、Catherine Li、Sergio H. Szajnman、Roberto Docampo、Silvia N. J. Moreno、Juan B. Rodriguez

  DOI：10.1002/cmdc.201500100

  日期：2015.6

  intracellular T. cruzi, whereas they showed potent action against tachyzoites of T. gondii (ED50 values of 1.6 and 1.9 μM against T. gondii). In addition, analogues of WC‐9 in which the terminal aryl group is in the meta position with respect to the alkyl chain bearing the thiocyanate group showed potent inhibitory action against both T. cruzi and T. gondii at the very low micromolar range, which suggests

  作为我们旨在寻找针对寄生虫病的新型安全化疗药物的项目的一部分，设计、合成了几种结构上与抗寄生虫药物 WC-9（4-苯氧基苯氧基乙基硫氰酸酯）相关的化合物，这些化合物在末端苯环上进行了修饰，并被评估为针对克氏锥虫（恰加斯病的病原体）和弓形虫（引起弓形体病的寄生虫）的生长抑制剂。大多数合成类似物表现出相似的抗寄生虫活性，并且比我们的先导 WC-9 稍强一些。例如，两种三氟甲基化衍生物针对细胞内克氏弓形虫表现出 10.0 和 9.2 μM的 ED 50值，而针对弓形虫速殖子表现出有效的作用（针对弓形虫的 ED 50值为 1.6 和 1.9 μM ）。此外，末端芳基位于带有硫氰酸酯基团的烷基链间位的 WC-9 类似物在非常低的微摩尔范围内对克氏弓形虫和刚地弓形虫均表现出有效的抑制作用。表明对苯基取代模式对于生物活性来说不是必需的。