2-(adamantan-1-yl)-6,8-dichloroquinoline-4-carboxylic acid | 49647-91-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(adamantan-1-yl)-6,8-dichloroquinoline-4-carboxylic acid
• 英文别名: 2-adamantan-1-yl-6,8-dichloro-quinoline-4-carboxylic acid；6,8-Dichlor-2-(1-adamantyl)-cinchoninsaeure；6,8-Dichloro-2-(1-adamantanyl)-4-quinolinecarboxylic acid；2-(1-adamantyl)-6,8-dichloroquinoline-4-carboxylic acid
• CAS: 49647-91-8
• 化学式: C₂₀H₁₉Cl₂NO₂
• 分子量: 376.282
• InChiKey: UBEOXBXGCAWKSO-UHFFFAOYSA-N

物化性质

• 沸点：
  543.9±50.0 °C(Predicted)
• 密度：
  1.435±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(adamantan-1-yl)-6,8-dichloroquinoline-4-carboxylic acid 在 氯化亚砜 、 硼烷四氢呋喃络合物 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 103.0h， 生成 2-((E)-6-(2-(adamantan-1-yl)-6,8-dichloroquinolin-4-yl)hex-5-en-1-yl)isoindoline-1,3-dione
  参考文献：
  名称：

  Synthesis and initial evaluation of quinoline-based inhibitors of the SH2-containing inositol 5′-phosphatase (SHIP)

  摘要：

  Recently, inhibition of the SH2-containing inositol 5'-phosphatase 1 (SHIP1) has become an attractive strategy for facilitating engraftment of MHC-I mismatched bone marrow grafts, increasing the number of adult stem cells in vivo, and inducing mobilization of hematopoietic stem cells. Utilizing high-throughput screening, two quinoline small molecules (NSC13480 and NSC305787) that inhibit SHIP1 enzymatic activity were discovered. New syntheses of these inhibitors have been developed which verified the relative stereochemistry of these structures. Utilizing this synthetic route, some analogs of these quinolines have been prepared and tested for their ability to inhibit SHIP. These structure activity studies determined that an amine tethered to the quinoline core is required for SHIP inhibition. SHIP inhibition may explain the antitumor effects of similar quinoline amino alcohols and provides an impetus for further synthetic studies in this class of compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.034
• 作为产物：
  描述：

  1-金刚烷甲酸 在 甲基锂 、 potassium hydroxide 作用下， 以 乙醚 、 乙醇 、 水 为溶剂， 反应 49.0h， 生成 2-(adamantan-1-yl)-6,8-dichloroquinoline-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and initial evaluation of quinoline-based inhibitors of the SH2-containing inositol 5′-phosphatase (SHIP)

  摘要：

  Recently, inhibition of the SH2-containing inositol 5'-phosphatase 1 (SHIP1) has become an attractive strategy for facilitating engraftment of MHC-I mismatched bone marrow grafts, increasing the number of adult stem cells in vivo, and inducing mobilization of hematopoietic stem cells. Utilizing high-throughput screening, two quinoline small molecules (NSC13480 and NSC305787) that inhibit SHIP1 enzymatic activity were discovered. New syntheses of these inhibitors have been developed which verified the relative stereochemistry of these structures. Utilizing this synthetic route, some analogs of these quinolines have been prepared and tested for their ability to inhibit SHIP. These structure activity studies determined that an amine tethered to the quinoline core is required for SHIP inhibition. SHIP inhibition may explain the antitumor effects of similar quinoline amino alcohols and provides an impetus for further synthetic studies in this class of compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.034

文献信息

• Synthesis and initial evaluation of quinoline-based inhibitors of the SH2-containing inositol 5′-phosphatase (SHIP)
  作者：Christopher M. Russo、Arijit A. Adhikari、Daniel R. Wallach、Sandra Fernandes、Amanda N. Balch、William G. Kerr、John D. Chisholm

  DOI：10.1016/j.bmcl.2015.09.034

  日期：2015.11

  Recently, inhibition of the SH2-containing inositol 5'-phosphatase 1 (SHIP1) has become an attractive strategy for facilitating engraftment of MHC-I mismatched bone marrow grafts, increasing the number of adult stem cells in vivo, and inducing mobilization of hematopoietic stem cells. Utilizing high-throughput screening, two quinoline small molecules (NSC13480 and NSC305787) that inhibit SHIP1 enzymatic activity were discovered. New syntheses of these inhibitors have been developed which verified the relative stereochemistry of these structures. Utilizing this synthetic route, some analogs of these quinolines have been prepared and tested for their ability to inhibit SHIP. These structure activity studies determined that an amine tethered to the quinoline core is required for SHIP inhibition. SHIP inhibition may explain the antitumor effects of similar quinoline amino alcohols and provides an impetus for further synthetic studies in this class of compounds. (C) 2015 Elsevier Ltd. All rights reserved.