1-(2,4-dichlorophenyl)-2-(2H-tetrazol-2-yl)ethan-1-one | 220902-32-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2,4-dichlorophenyl)-2-(2H-tetrazol-2-yl)ethan-1-one
• 英文别名: 1-(2,4-dichlorophenyl)-2-tetrazol-2-yl-ethanone；1-(2,4-dichlorophenyl)-2-(tetrazol-2-yl)ethanone
• CAS: 220902-32-9
• 化学式: C₉H₆Cl₂N₄O
• 分子量: 257.079
• InChiKey: OLNGHNMEXQKLJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  60.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2,4-dichlorophenyl)-2-(2H-tetrazol-2-yl)ethan-1-one 在 三氟甲磺酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 64.0h， 生成 4-(4-(4-(4-(((2S,4R)-2-((2H-tetrazol-2-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-1-(sec-butyl)-1H-1,2,4-triazol-5(4H)-one
  参考文献：
  名称：

  Novel Tetrazole-Containing Analogues of Itraconazole as Potent Antiangiogenic Agents with Reduced Cytochrome P450 3A4 Inhibition

  摘要：

  Itraconazole has been found to possess potent antiangiogenic activity, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). In an effort to eliminate the CYP3A4 inhibition while retaining its antiangiogenic activity, we designed and synthesized a series of derivatives in which the 1,2,4-triazole ring is replaced with various azoles and nonazoles. Among these analogues, 15n with tetrazole in place of 1,2,4-triazole exhibited optimal inhibition of human umbilical vein endothelial cell proliferation with an IC50 of 73 nM without a significant effect on CYP3A4 (EC50 > 20 mu M). Similar to itraconazole, 15n induced Niemann-Pick C phenotype (NPC phenotype) and blocked AMPK/mechanistic target of rapamycin signaling. These results suggest that 15n is a promising angiogenesis inhibitor that can be used in combination with most other known anticancer drugs.

  DOI：

  10.1021/acs.jmedchem.8b01252
• 作为产物：
  描述：

  1,3-二氯苯 在 aluminum (III) chloride 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 16.67h， 生成 1-(2,4-dichlorophenyl)-2-(2H-tetrazol-2-yl)ethan-1-one
  参考文献：
  名称：

  Novel Tetrazole-Containing Analogues of Itraconazole as Potent Antiangiogenic Agents with Reduced Cytochrome P450 3A4 Inhibition

  摘要：

  Itraconazole has been found to possess potent antiangiogenic activity, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). In an effort to eliminate the CYP3A4 inhibition while retaining its antiangiogenic activity, we designed and synthesized a series of derivatives in which the 1,2,4-triazole ring is replaced with various azoles and nonazoles. Among these analogues, 15n with tetrazole in place of 1,2,4-triazole exhibited optimal inhibition of human umbilical vein endothelial cell proliferation with an IC50 of 73 nM without a significant effect on CYP3A4 (EC50 > 20 mu M). Similar to itraconazole, 15n induced Niemann-Pick C phenotype (NPC phenotype) and blocked AMPK/mechanistic target of rapamycin signaling. These results suggest that 15n is a promising angiogenesis inhibitor that can be used in combination with most other known anticancer drugs.

  DOI：

  10.1021/acs.jmedchem.8b01252

文献信息

• Heterocyclic vinyl ethers
  申请人：Hoffman-La Roche Inc.

  公开号：US06054588A1

  公开（公告）日：2000-04-25

  The compounds of the formula ##STR1## wherein R signifies halogen or lower alkyl; n signifies 0-3; R.sup.1 signifies lower alkyl; cycloalkyl; benzyl optionally substituted by hydroxy, halogen, lower alkoxy or lower alkyl; benzoyl optionally substituted by amino, lower alkyl-amino or di-lower alkylamino; acetyl or cycloalkyl-carbonyl; and ##STR2## signifies an aromatic 5-membered residue which is bonded via a N-atom and which contains further 1-3 N atoms in addition to the linking N atom, as well as their pharmaceutically acceptable salts as therapeutically active substances, especially for the control or prevention of acute and/or chronic neurological disorders.

  该公式化合物的化合物##STR1##其中R表示卤素或较低的烷基；n表示0-3；R.sup.1表示较低的烷基；环烷基；苄基，可选择地被羟基，卤素，较低的烷氧基或较低的烷基取代；苯甲酰，可选择地被氨基，较低烷基氨基或双较低烷氨基取代；乙酰基或环烷基羰基；和##STR2##表示经由N原子键合的含有进一步1-3个N原子的芳香5-成员残基，除了连接的N原子外，以及它们的药用可接受的盐作为治疗活性物质，特别用于控制或预防急性和/或慢性神经系统疾病。
• A Three‐Step Chemoenzymatic Cascade Synthesis of Miconazole Analogues Based on the Asymmetric Synthesis of β‐Heteroaryl Amino Alcohols via Ketoreductases
  作者：Jiali Fang、Yiping Xu、Hanwen Ren、Chenming Huang、Wenhe Zhang、Xian Jia、Song You、Bin Qin

  DOI：10.1002/adsc.202300740

  日期：2023.12.5

  isolation of ketone and alcohol intermediates, and avoids the use of metal catalysts in the synthesis of chiral miconazole analogues. Furthermore, we successfully scaled up the preparation of (S)-miconazole, achieving a 30% isolated yield and >99% ee. This method presents a novel synthetic approach for production chiral ether drugs and chiral β-heteroaryl amino alcohols, offering new possibilities in pharmaceutical

  手性 β-杂芳基氨基醇作为中间体在许多生物活性药物的合成中发挥着至关重要的作用，包括西诺贝酯、奥替康唑和咪康唑。然而，缺乏文献记录建立合成β-杂芳基氨基醇和上述药物的通用方法。在这项研究中，我们使用两种具有相反立体选择性的工程酮还原酶（KRED）成功不对称合成了 50 对手性 β-杂芳基氨基醇。基于这一成果，我们开发了一种三步化学酶级联路线，用于从市售的 2-溴苯乙酮衍生物合成手性咪康唑类似物。通过优化第一步合成α-咪唑基酮的溶剂，然后在第二步中使用KREDs还原α-咪唑基酮，并在第三步中进行醚化，我们获得了20种具有良好产率的手性咪康唑类似物（26 –84%）和令人印象深刻的立体选择性（高达 >99% ee）。值得注意的是，该路线无需分离酮和醇中间体，并避免在手性咪康唑类似物的合成中使用金属催化剂。此外，我们成功放大了( S )-咪康唑的制备，实现了30%的分离收率和>99% ee。该方
• Synthesis of heterocyclic enol ethers and their use as group 2 metabotropic glutamate receptor antagonists
  作者：Sabine Kolczewski、Geo Adam、Heinz Stadler、Vincent Mutel、Jürgen Wichmann、Thomas Woltering

  DOI：10.1016/s0960-894x(99)00346-7

  日期：1999.8

  Heterocyclic enol ethers of type 1 were studied with respect to the inhibition of 1S,3R-ACPD (10 mu M)stimulated GTP gamma(35)S binding on rat mGluR2 transfected cell membranes. The structure activity relationship with regard to the substitution pattern of the phenyl ring, the oxygen substituent and the nature of the heterocycle is discussed, (C) 1999 Elsevier Science Ltd. All rights reserved.
• HETEROCYCLIC VINYLETHERS AGAINST NEUROLOGICAL DISORDERS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1003505A1

  公开（公告）日：2000-05-31
• US6054588A
  申请人：——

  公开号：US6054588A

  公开（公告）日：2000-04-25