(4,4’-(ethyne-1,2-diyl)bis(4,1-phenylene))dimethanol | 84907-57-3

• 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: (4,4’-(ethyne-1,2-diyl)bis(4,1-phenylene))dimethanol
• 英文别名: [4-(4-Hydroxymethyl-phenylethynyl)-phenyl]-methanol；[4-[2-[4-(hydroxymethyl)phenyl]ethynyl]phenyl]methanol
• CAS: 84907-57-3
• 化学式: C₁₆H₁₄O₂
• 分子量: 238.286
• InChiKey: RTXVVHMNRAUUPK-UHFFFAOYSA-N

物化性质

• 熔点：
  198 °C
• 沸点：
  448.7±40.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4,4’-(ethyne-1,2-diyl)bis(4,1-phenylene))dimethanol 在 2,4,6-三甲基氯苯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以80%的产率得到
  参考文献：
  名称：

  通过[2 + 2 + 2]炔烃环三聚过程 从[3]轮烷向六支链的[7]轮烷烷†

  摘要：

  通过使用从[3]轮烷中共催化的[2 + 2 + 2]炔烃环三聚，已经获得了一种基于冠醚的六支[7]轮烷的合成方法。[2 + 2 + 2]炔烃环三聚过程仅需要10 mol％的Co 2（CO）8作为催化剂，并能有效生产目标轮烷，这是构建高度复杂的树枝状轮烷的一种新策略。

  DOI：

  10.1039/c9cc00363k
• 作为产物：
  描述：

  二(4-溴苯基)乙炔 在 盐酸 、 sodium tetrahydroborate 、 正丁基锂 作用下， 以 乙醇 为溶剂， 生成 (4,4’-(ethyne-1,2-diyl)bis(4,1-phenylene))dimethanol
  参考文献：
  名称：

  Raston, Ilona; Wennerstroem, Olof, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1982, vol. 36, # 10, p. 655 - 660

  摘要：

  DOI：

文献信息

• ORGANIC COMPOUNDS TO TREAT HEPATITIS B VIRUS
  申请人：Baryza Jeremy Lee

  公开号：US20160215288A1

  公开（公告）日：2016-07-28

  The disclosure relates to compositions comprising a HBV RNAi agent. In some embodiments, the HBV RNAi agent comprises a sense and an anti-sense strand, each strand being an 18-mer and the strands together forming a blunt-ended duplex, wherein the 3′ end of at least one strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5′ to 3′ order: a spacer; a second phosphate or modified internucleoside linker; and a 3′ end cap. In some embodiments, the 3′ end of both the sense and anti-sense strand further comprise, in 5′ to 3′ order: a spacer; a second phosphate or modified internucleoside linker; and a 3′ end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3′ end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the RNAi agent can be modified on one or both 5′ end. Optionally, the sense strand can comprise a 5′ end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference. The disclosure also pertains to methods of treating, ameliorating and preventing HBV in a patient involving the step of administering to the patient a therapeutic amount of a HBV RNAi agent.

  该披露涉及包含HBV RNAi药剂的组合物。在某些实施例中，HBV RNAi药剂包括一个正义链和一个反义链，每个链都是18个核苷酸长，并且这些链一起形成一个带有钝端的双链，其中至少一个链的3'端终止于磷酸酯或修饰的核苷酸间连接物，并且进一步包括，按照5'到3'的顺序：一个间隔物；第二个磷酸酯或修饰的核苷酸间连接物；和一个3'端帽。在某些实施例中，正义链和反义链的3'端进一步包括，按照5'到3'的顺序：一个间隔物；第二个磷酸酯或修饰的核苷酸间连接物；和一个3'端帽。这两个链可以具有相同或不同的间隔物、磷酸酯或修饰的核苷酸间连接物，和/或3'端帽。这些链可以是核糖核苷酸，或者，可选地，一个或多个核苷酸可以被修饰或替代。可选地，至少一个核苷酸包括一个修饰的核苷酸间连接物。可选地，RNAi药剂可以在一个或两个5'端上被修饰。可选地，正义链可以包括减少由该链介导的RNA干扰量的5'端帽。可选地，RNAi药剂附着在一个配体上。这种格式可以用来设计针对各种不同靶标和序列的RNAi药剂。该披露还涉及制备这种组合物的方法，以及这种组合物的方法和用途，例如，用于介导RNA干扰。该披露还涉及涉及将治疗量的HBV RNAi药剂给患者的步骤来治疗、改善和预防患者体内的HBV的方法。
• Twisting of Alkynes towards a Carbon Double Helix
  作者：Abdulselam Adam、Gebhard Haberhauer

  DOI：10.1002/chem.201701096

  日期：2017.9.7

  only one-dimensional sp-hybridized carbon atoms is called carbyne. However, its existence is very controversial. Studies on model compounds for carbyne revealed that many oligoalkynes show not a straight, but a bent structure of the carbon chain. Here, we question whether it would also be possible to obtain a more complex structure from carbyne, such as a dimeric double helix. Based on quantum chemical

  仅表现出一维sp杂化碳原子的碳同素异形体称为卡宾。但是，它的存在是很有争议的。研究的卡宾化合物模型表明，许多oligoalkynes显示不碳链的直的但弯曲的结构。在这里，我们质疑是否还可能从卡宾获得更复杂的结构，例如二聚体双螺旋。基于量子化学计算，我们表明从低炔烃链开始形成双螺旋仅需要少量的能量消耗。在某些情况下，双螺旋状构象比具有平行排列的乙炔链的相应构象更稳定。此外，合成了模型系统，其中两个二苯基低炔烃链被固定并且通过含手性咪唑的夹具被扭曲。这些模型系统的结构研究是基于UV和CD光谱学和量子化学计算进行的。
• NOVEL FORMATS FOR ORGANIC COMPOUNDS FOR USE IN RNA INTERFERENCE
  申请人：BARYZA Jeremy Lee

  公开号：US20160244756A1

  公开（公告）日：2016-08-25

  The disclosure relates to compositions comprising a RNAi agent having a novel format including a spacer subunit. The disclosure relates to compositions comprising a RNAi agent having a novel format: an 18-mer format with at least one internal spacer. These RNAi agents comprise a first and a second 18-mer strand, wherein the first strand is 18 ribonucleotides or 18 total ribonucleotides and spacer subunit(s), and the second strand is 18 total ribonucleotides and spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand; the two strands form a duplex with at least one blunt end; and the 3 end of one or both strands terminates in a phosphate or modified internucleoside linker and further comprises, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker, and a 3 end cap. In various embodiments, the RNAi agents comprise a first and a second strand, wherein each strand is a 30-mer or shorter, the first strand comprises ribonucleotides, and the second strand comprises ribonucleotides and one or more spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer; a spacer subunit can be at any position in the strand. In some embodiments, the 3 end of both strands further comprise, in 5 to 3 order: a second spacer; a second phosphate or modified internucleoside linker; and a 3 end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3 end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the first two base-pairing nucleotides on the 3 end of the one or both strand are 2-MOE. Optionally, the RNAi agent can be modified on one or both 5 end. Optionally, the first or second strand is the sense strand, and the sense strand can comprise a 5 end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.

  本公开涉及包含具有新型格式的RNAi药剂的组合物，其中包括一个间隔亚基。本公开涉及包括具有新型格式的RNAi药剂的组合物：具有至少一个内部间隔的18-mer格式。这些RNAi药剂包括第一和第二个18-mer链，其中第一链是18个核苷酸或18个总核苷酸和间隔亚基，第二链是18个总核苷酸和间隔亚基，其中：每个间隔亚基由(a)磷酸酯或修饰的核苷酸间连体和(b)间隔组成；间隔亚基可以在链的任何位置；两个链形成至少一个钝端的双链；并且一个或两个链的3'端以磷酸酯或修饰的核苷酸间连体终止，并进一步包括，以5到3的顺序：第二个间隔；第二个磷酸酯或修饰的核苷酸间连体，以及3'端帽。在各种实施例中，RNAi药剂包括第一和第二链，其中每个链是30-mer或更短，第一链包括核苷酸，第二链包括核苷酸和一个或多个间隔亚基，其中：每个间隔亚基由(a)磷酸酯或修饰的核苷酸间连体和(b)间隔组成；间隔亚基可以在链的任何位置。在某些实施例中，两个链的3'端进一步包括，以5到3的顺序：第二个间隔；第二个磷酸酯或修饰的核苷酸间连体；和3'端帽。两个链可以具有相同或不同的间隔、磷酸酯或修饰的核苷酸间连体和/或3'端帽。链可以是核苷酸，或者可选地，一个或多个核苷酸可以被修饰或替换。可选地，至少一个核苷酸包含修饰的核苷酸间连体。可选地，一个或两个链的3'端的前两个配对核苷酸是2-MOE。可选地，RNAi药剂可以在一个或两个5'端上被修饰。可选地，第一或第二链是正义链，正义链可以包括减少由该链介导的RNA干扰的5'端帽。可选地，RNAi药剂附着在配体上。此格式可用于设计针对各种不同靶标和序列的RNAi药剂。本公开还涉及制备这种组合物的过程，以及这种组合物的方法和用途，例如介导RNA干扰。
• 3′end caps for RNAi agents for use in RNA interference
  申请人：Novartis AG

  公开号：US10227588B2

  公开（公告）日：2019-03-12

  The disclosure relates to novel compounds and compositions comprising a RNAi agent comprising a novel compound as a 3′ end cap. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.

  本公开涉及新型化合物和组合物，该组合物包含作为 3′端盖的新型化合物的 RNAi 剂。本发明还涉及制造这种组合物的工艺，以及这种组合物的方法和用途，如介导 RNA 干扰。
• Organic compounds to treat hepatitis B virus
  申请人：Novartis AG

  公开号：US10519446B2

  公开（公告）日：2019-12-31

  The disclosure relates to compositions comprising a HBV RNAi agent. In some embodiments, the HBV RNAi agent comprises a sense and an anti-sense strand, each strand being an 18-mer and the strands together forming a blunt-ended duplex, wherein the 3′ end of at least one strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5′ to 3′ order: a spacer; a second phosphate or modified internucleoside linker; and a 3′ end cap. In some embodiments, the 3′ end of both the sense and anti-sense strand further comprise, in 5′ to 3′ order: a spacer; a second phosphate or modified internucleoside linker; and a 3′ end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3′ end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the RNAi agent can be modified on one or both 5′ end. Optionally, the sense strand can comprise a 5′ end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference. The disclosure also pertains to methods of treating, ameliorating and preventing HBV in a patient involving the step of administering to the patient a therapeutic amount of a HBV RNAi agent.

  本公开涉及包含 HBV RNAi 剂的组合物。在一些实施方案中，HBV RNAi 剂包括有义链和无义链，每条链都是 18-mer，这些链一起形成钝端双链，其中至少一条链的 3′端终止于磷酸或修饰的核苷间连接体，并按 5′至 3′的顺序进一步包括：间隔物；第二个磷酸或修饰的核苷间连接体；以及 3′端盖。在某些实施方案中，有义链和反义链的 3′端按 5′至 3′的顺序进一步包括：间隔物；第二个磷酸或修饰的核苷连接物；以及 3′端盖。两条链可以具有相同或不同的间隔物、磷酸或修饰的核苷连接物和/或 3′端盖。链可以是核糖核苷酸，也可以是经过修饰或取代的一种或多种核苷酸。可选地，至少一种核苷酸包括修饰的核苷间连接体。可选地，RNAi 剂可以在一个或两个 5′端进行修饰。可选地，有义链可包括一个 5′端盖，它可减少由该链介导的 RNA 干扰量。可选地，RNAi 剂附着在配体上。这种形式可用于设计针对各种不同靶标和序列的 RNAi 制剂。本公开还涉及制造这种组合物的工艺，以及这种组合物的方法和用途，例如介导 RNA 干扰。本发明还涉及治疗、改善和预防患者 HBV 的方法，包括向患者施用治疗量的 HBV RNAi 制剂。