4-(4-(trimethylsilyl)but-3-yn-1-yl)pyridine | 1595282-02-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(4-(trimethylsilyl)but-3-yn-1-yl)pyridine
• 英文别名: Trimethyl(4-pyridin-4-ylbut-1-ynyl)silane；trimethyl(4-pyridin-4-ylbut-1-ynyl)silane
• CAS: 1595282-02-2
• 化学式: C₁₂H₁₇NSi
• 分子量: 203.359
• InChiKey: QGZSANIYJOABJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-(4-(trimethylsilyl)but-3-yn-1-yl)pyridine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 以64 mg的产率得到4-丁-3-炔基吡啶
  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-甲基吡啶 、 3-溴-1-三甲基硅基-1-丙炔 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.92h， 以23%的产率得到4-(4-(trimethylsilyl)but-3-yn-1-yl)pyridine
  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

文献信息

• Copper-Catalyzed Monoborylation of Silylalkynes; Regio- and Stereoselective Synthesis of (<i>Z</i>)-β-(Borylvinyl)silanes
  作者：Yeong Mi Chae、Jun Sung Bae、Jong Hun Moon、Jin Yong Lee、Jaesook Yun

  DOI：10.1002/adsc.201300881

  日期：2014.3.10

  The selective copper‐catalyzed borylation of silylalkynes in the presence of a diboron reagent and methanol produced a variety of (Z)‐β‐(borylvinyl)silanes. The appropriate use of a selective ligand for copper allows the chemo‐, regio‐, and stereoselective monoborylation of silylalkynes. The β‐regioselectivity of an N‐heterocyclic carbene (NHC)‐copper catalyst was investigated by DFT calculations.

  在存在二硼试剂和甲醇的情况下，铜催化的甲硅烷基炔烃的选择性硼化反应生成了各种（Z）-β-（硼乙烯基乙烯基）硅烷。铜的选择性配体的适当使用可实现甲硅烷基炔的化学，区域和立体选择性单硼化。通过DFT计算研究了N-杂环卡宾（NHC）-铜催化剂的β-区域选择性。
• 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.