5-(but-3-yn-1-yl)-1H-tetrazole | 954371-22-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(but-3-yn-1-yl)-1H-tetrazole
• 英文别名: 5-but-3-ynyl-1H-tetrazole；5-but-3-ynyl-2H-tetrazole
• CAS: 954371-22-3
• 化学式: C₅H₆N₄
• 分子量: 122.129
• InChiKey: XUVHXPCGYCQQSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(but-3-yn-1-yl)-1H-tetrazole 、 di-tert-butyl 8,8′-(((5-Iodo-1,3-phenylene)bis(methylene))bis-(oxy))(11S,11aS,11′S,11a′S)-bis(11-hydroxy-7-methoxy-2-methylene-5-oxo-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]-diazepine-10(5H)-carboxylate) 在 copper(l) iodide 、 四(三苯基膦)钯 、 二乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Systematic Variation of Pyrrolobenzodiazepine (PBD)-Dimer Payload Physicochemical Properties Impacts Efficacy and Tolerability of the Corresponding Antibody–Drug Conjugates

  摘要：

  Cytotoxic pyrrolobenzodiazepine (PBD)-dimer molecules are frequently utilized as payloads for antibody-drug conjugates (ADCs), and many examples are currently in clinical development. In order to further explore this ADC payload class, the physicochemical properties of various PBD-dimer molecules were modified by the systematic introduction of acidic and basic moieties into their chemical structures. The impact of these changes on DNA binding, cell membrane permeability, and in vitro antiproliferation potency was, respectively, determined using a DNA alkylation assay, PAMPA assessments, and cell-based cytotoxicity measurements conducted with a variety of cancer lines. The modified PBD-dimer compounds were subsequently incorporated into CD22-targeting ADCs, and these entities were profiled in a variety of in vitro and in vivo experiments. The introduction of a strongly basic moiety into the PBD-dimer scaffold afforded a conjugate with dramatically worsened mouse tolerability properties relative to ADCs derived from related payloads, which lacked the basic group.

  DOI：

  10.1021/acs.jmedchem.0c00691
• 作为产物：
  描述：

  4-氰基-1-丁炔 在 sodium azide 、 三乙胺盐酸盐 作用下， 以 甲苯 为溶剂， 反应 9.5h， 以49%的产率得到5-(but-3-yn-1-yl)-1H-tetrazole
  参考文献：
  名称：

  具有增强的水解稳定性的烯基二芳基甲烷HIV-1非核苷逆转录酶抑制剂的合成和生物学评估。

  摘要：

  HIV逆转录酶（NNRTIs）的非核苷抑制剂尽管不是HIV / AIDS治疗的主要手段，但由于其独特的作用机理，在高活性抗逆转录病毒疗法（HAART）中已变得越来越重要。几年前，我们的研究小组将烯基二芳基甲烷（ADAMs）鉴定为一种有效的新型NNRTIs。然而，发现活性最高的化合物在代谢上不稳定。随后的工作通过用各种杂环，腈和硫代酯代替不稳定的酯，从而合成了33种具有改善的代谢特性的类似物。结果，在纳摩尔浓度范围内鉴定出许多具有抗HIV活性的水解稳定的NNRTI。此外，基于新的ADAM系列，开发了一种改进的药效团模型，

  DOI：

  10.1021/jm070382k

文献信息

• Synthesis and Biological Evaluation of Alkenyldiarylmethane HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors That Possess Increased Hydrolytic Stability
  作者：Matthew D. Cullen、Bo-Liang Deng、Tracy L. Hartman、Karen M. Watson、Robert W. Buckheit,、Christophe Pannecouque、Erik De Clercq、Mark Cushman

  DOI：10.1021/jm070382k

  日期：2007.10.1

  Non-nucleoside inhibitors of HIV reverse transcriptase (NNRTIs), albeit not the mainstays of HIV/AIDS treatment, have become increasingly important in highly active antiretroviral therapy (HAART) due to their unique mechanism of action. Several years ago our group identified the alkenyldiarylmethanes (ADAMs) as a potent and novel class of NNRTIs; however, the most active compounds were found to be

  HIV逆转录酶（NNRTIs）的非核苷抑制剂尽管不是HIV / AIDS治疗的主要手段，但由于其独特的作用机理，在高活性抗逆转录病毒疗法（HAART）中已变得越来越重要。几年前，我们的研究小组将烯基二芳基甲烷（ADAMs）鉴定为一种有效的新型NNRTIs。然而，发现活性最高的化合物在代谢上不稳定。随后的工作通过用各种杂环，腈和硫代酯代替不稳定的酯，从而合成了33种具有改善的代谢特性的类似物。结果，在纳摩尔浓度范围内鉴定出许多具有抗HIV活性的水解稳定的NNRTI。此外，基于新的ADAM系列，开发了一种改进的药效团模型，
• WO2008/119028
  申请人：——

  公开号：——

  公开（公告）日：——
• Systematic Variation of Pyrrolobenzodiazepine (PBD)-Dimer Payload Physicochemical Properties Impacts Efficacy and Tolerability of the Corresponding Antibody–Drug Conjugates
  作者：Leanna R. Staben、Jinhua Chen、Josefa dela Cruz-Chuh、Geoff del Rosario、Mary Ann Go、Jun Guo、S. Cyrus Khojasteh、Katherine R. Kozak、Guangmin Li、Carl Ng、Gail D. Lewis Phillips、Thomas H. Pillow、Rebecca K. Rowntree、John Wai、BinQing Wei、Keyang Xu、Zijin Xu、Shang-Fan Yu、Donglu Zhang、Peter S. Dragovich

  DOI：10.1021/acs.jmedchem.0c00691

  日期：2020.9.10

  Cytotoxic pyrrolobenzodiazepine (PBD)-dimer molecules are frequently utilized as payloads for antibody-drug conjugates (ADCs), and many examples are currently in clinical development. In order to further explore this ADC payload class, the physicochemical properties of various PBD-dimer molecules were modified by the systematic introduction of acidic and basic moieties into their chemical structures. The impact of these changes on DNA binding, cell membrane permeability, and in vitro antiproliferation potency was, respectively, determined using a DNA alkylation assay, PAMPA assessments, and cell-based cytotoxicity measurements conducted with a variety of cancer lines. The modified PBD-dimer compounds were subsequently incorporated into CD22-targeting ADCs, and these entities were profiled in a variety of in vitro and in vivo experiments. The introduction of a strongly basic moiety into the PBD-dimer scaffold afforded a conjugate with dramatically worsened mouse tolerability properties relative to ADCs derived from related payloads, which lacked the basic group.