4-phenylsulfanylphenoxyethyl tetrahydro-2H-pyran-2-yl ether | 445283-57-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-phenylsulfanylphenoxyethyl tetrahydro-2H-pyran-2-yl ether
• 英文别名: 4-(phenylthio)phenoxyethyl tetrahydro-2H-pyran-2-yl ether；2-[2-(4-Phenylsulfanylphenoxy)ethoxy]oxane
• CAS: 445283-57-8
• 化学式: C₁₉H₂₂O₃S
• 分子量: 330.448
• InChiKey: HGWTWUJMDRHATO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-phenylsulfanylphenoxyethyl tetrahydro-2H-pyran-2-yl ether 在 吡啶 、 甲醇 、 sodium periodate 、 4-甲基苯磺酸吡啶 作用下， 以 甲醇 、 水 为溶剂， 反应 68.0h， 生成 4-phenylsulfinylphenoxyethyl 4-toluenesulfonate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Aryloxyethyl Thiocyanate Derivatives against Trypanosoma cruzi

  摘要：

  As a continuation of our project aimed at the search for new and safe chemotherapeutic and chemoprophylactic agents against American trypanosomiasis (Chagas' disease), several drugs structurally related to 4-phenoxyphenoxyethyl thiocyanate (4) were designed, synthesized, and evaluated as antiproliferative agents against the parasite responsible for this disease, the hemoflagellated protozoan Trypanosoma cruzi. This thiocyanate derivative was previously shown to be an effective and potent agent against T. cruzi proliferation. Several drugs possessing thiocyanate groups proved to be effective growth inhibitors of T. cruzi growth. Among the designed compounds, it is important to point out the extremely potent activity shown by 11, 23, 38, 53, 90, 99, and 117 against the epimastigote forms of the parasite. All of them exhibited IC50 values in the low micromolar range, and these values were comparable with those presented by our lead drug 4 and ketokonazole, a well-known antiparasitic agent. The activity displayed by the nitrogen-containing derivative 90 was very promising with IC50 values of 3.3 muM. Several other thiocyanate derivatives also proved to be very potent inhibitors of the multiplication of T. cruzi epimastigotes, such as compounds 28, 33, 43, 48, 56, 61, 66, 71, 76, and 124. Compound 43 resulted in being a promising drug because it was also very effective against amastigotes, the clinically more relevant form of the parasite. This compound was Mold more potent than 4, while 11 showed nearly the same activity as our lead drug against intracellular T. cruzi. It was very surprising that the experimental juvenoid 124, although fairly devoid of activity against epimastigotes, was very effective against intracellular amastigotes growing in myoblasts. The rest of the designed compounds showed a broad degree of inhibitory action, from moderately active drugs to drugs almost devoid of antiparasitic activity. Compound 43 is an interesting example of an effective antichagasic agent that presents excellent prospectives not only as a lead drug but also to be used for further in vivo studies.

  DOI：

  10.1021/jm0201518
• 作为产物：
  描述：

  2-(2-溴乙氧基)四氢吡喃 、 4-羟基苯基苯硫醚 在 氢氧化钾 作用下， 以 二甲基亚砜 为溶剂， 反应 16.08h， 以62%的产率得到4-phenylsulfanylphenoxyethyl tetrahydro-2H-pyran-2-yl ether
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Aryloxyethyl Thiocyanate Derivatives against Trypanosoma cruzi

  摘要：

  As a continuation of our project aimed at the search for new and safe chemotherapeutic and chemoprophylactic agents against American trypanosomiasis (Chagas' disease), several drugs structurally related to 4-phenoxyphenoxyethyl thiocyanate (4) were designed, synthesized, and evaluated as antiproliferative agents against the parasite responsible for this disease, the hemoflagellated protozoan Trypanosoma cruzi. This thiocyanate derivative was previously shown to be an effective and potent agent against T. cruzi proliferation. Several drugs possessing thiocyanate groups proved to be effective growth inhibitors of T. cruzi growth. Among the designed compounds, it is important to point out the extremely potent activity shown by 11, 23, 38, 53, 90, 99, and 117 against the epimastigote forms of the parasite. All of them exhibited IC50 values in the low micromolar range, and these values were comparable with those presented by our lead drug 4 and ketokonazole, a well-known antiparasitic agent. The activity displayed by the nitrogen-containing derivative 90 was very promising with IC50 values of 3.3 muM. Several other thiocyanate derivatives also proved to be very potent inhibitors of the multiplication of T. cruzi epimastigotes, such as compounds 28, 33, 43, 48, 56, 61, 66, 71, 76, and 124. Compound 43 resulted in being a promising drug because it was also very effective against amastigotes, the clinically more relevant form of the parasite. This compound was Mold more potent than 4, while 11 showed nearly the same activity as our lead drug against intracellular T. cruzi. It was very surprising that the experimental juvenoid 124, although fairly devoid of activity against epimastigotes, was very effective against intracellular amastigotes growing in myoblasts. The rest of the designed compounds showed a broad degree of inhibitory action, from moderately active drugs to drugs almost devoid of antiparasitic activity. Compound 43 is an interesting example of an effective antichagasic agent that presents excellent prospectives not only as a lead drug but also to be used for further in vivo studies.

  DOI：

  10.1021/jm0201518

文献信息

• Selenium-containing analogues of WC-9 are extremely potent inhibitors of Trypanosoma cruzi proliferation
  作者：María N. Chao、Melissa Storey、Catherine Li、Maricel G. Rodríguez、Florencia Di Salvo、Sergio H. Szajnman、Silvia N.J. Moreno、Roberto Docampo、Juan B. Rodriguez

  DOI：10.1016/j.bmc.2017.10.016

  日期：2017.12

  Chagas disease. Especially, inhibitors of the enzymatic activity of squalene synthase were shown to be effective compounds on T. cruzi proliferation in in vitro assays. In the present study we designed, synthesized and evaluated the effect of a number of isosteric analogues of WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, on T. cruzi growth in tissue culture cells. The

  独占的细胞内寄生虫克氏锥虫是南美锥虫病或美洲锥虫病的病原体，锥虫病是美洲最流行的寄生虫病。目前控制这种疾病的化学疗法仍然是不足的，特别是在该疾病的慢性阶段。麦角固醇的生物合成途径作为查加斯病新药开发的分子靶标受到了广泛关注。特别是，在体外试验中，角鲨烯合酶的酶活性抑制剂被证明是有效的克氏锥虫增殖化合物。在本研究中，我们设计，合成和评估了WC-9的许多等规类似物的作用（4-苯氧基苯氧基乙基硫氰酸盐），一种已知的角鲨烯合酶抑制剂，对组织培养细胞中的克鲁氏锥虫生长。事实证明，含硒衍生物是克鲁维酵母生长的极强抑制剂。当然，出现了3-苯氧基苯氧基乙基，4-苯氧基苯氧基乙基，4-（3-氟苯氧基）苯氧基乙基，3-（3-氟苯氧基）苯氧基乙基硒氰酸酯和（±）-5-苯氧基-2-（硒代氰基甲基）-2,3-二氢苯并呋喃。该化合物家族的相关成员，表现出有效的ED 50值分别为0.084 µM，0.11 µM，0.083，µM，0