(2-(adamantan-1-yl)-6,8-dichloroquinolin-4-yl)(piperidin-2-yl)methanol

• 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-dichloroquinolin-4-yl)(piperidin-2-yl)methanol
• 英文别名: [2-(1-Adamantyl)-6,8-dichloroquinolin-4-yl]-piperidin-2-ylmethanol
• 化学式: C₂₅H₃₀Cl₂N₂O
• 分子量: 445.432
• InChiKey: YNGQUUFYBFKLNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  45.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2-(adamantan-1-yl)-6,8-dichloroquinolin-4-yl)(piperidin-2-yl)methanol 在 盐酸 作用下， 以 乙醚 为溶剂， 以60%的产率得到PKC抑制剂(NSC305787HYDROCHLORIDE)
  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：

  2-(4-(3-(2-(adamantan-1-yl)-6,8-dichloroquinolin-4-yl)oxiran-2-yl)butyl)isoindoline-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以62%的产率得到(2-(adamantan-1-yl)-6,8-dichloroquinolin-4-yl)(piperidin-2-yl)methanol
  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

• NOVEL EZRIN INHIBITORS AND METHODS OF MAKING AND USING
  申请人：GEORGETOWN UNIVERSITY

  公开号：US20140135325A1

  公开（公告）日：2014-05-15

  The invention encompasses compound and pharmaceutical composition comprising the compound of the following Formula (I): or pharmaceutically acceptable salts or prodrugs thereof, that are useful for inhibiting ezrin protein in a cell or for inhibiting the growth of a cancer cell.
• 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.