NK 10958P

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: NK 10958P
• 英文别名: (2R,3R)-2-[(E,2R,3S,4R,5S)-2,4-dihydroxy-3,5-dimethylnon-7-enyl]-3-ethyl-2,3-dihydropyran-6-one
• 化学式: C₁₈H₃₀O₄
• 分子量: 310.434
• InChiKey: DGTXWIIFBBXJAA-BZQBGSLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-乙基-5,6-二氢-6-[(2R,3S,4R,5S,7E)-2-羟基-4-甲氧基-3,5-二甲基-7-壬烯-1-基]-,(5R,6R)-2H-吡喃-2-酮 在 15-冠醚-5 、 三溴化硼 、 sodium iodide 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以57%的产率得到NK 10958P
  参考文献：
  名称：

  Identification of the Metabolic Profile of the α-Tubulin-Binding Natural Product (−)–Pironetin

  摘要：

  Pironetin, the only crystallographically confirmed natural product to target a-tubulin, displays potent cytotoxic activity against sensitive and resistant A2780 ovarian cancer cell lines but is only marginally active in vivo. We now report that pironetin has a short half-life (<7 min) in human liver microsomes, suggesting that its limited in vivo efficacy is due to rapid metabolism. Further, we describe the discovery of epoxypironetin as pironetin's major metabolite in human liver microsomes.

  DOI：

  10.1021/acs.jmedchem.8b01774

文献信息

• Small molecule immunopotentiators and assays for their detection
  申请人：Novartis Vaccines and Diagnostics, Inc.

  公开号：EP2583678A2

  公开（公告）日：2013-04-24

  The invention provides immunostimulatory compositions comprising a small molecule immuno-potentiator (SMIP) compound and methods of administration thereof. Also provided are methods of administering a SMIP compound in an effective amount to enhance the immune response of a subject to an antigen. Further provided are novel compositions and methods of administering SMIP compounds alone or in combination with another agent for the treatment of cancer, infectious diseases and/or allergies/asthma. In a further aspect, the invention relates generally to methods of screening for small molecule immuno-modulatory compositions.

  本发明提供了包含小分子免疫促进剂（SMIP）化合物的免疫刺激组合物及其施用方法。还提供了施用有效量的 SMIP 化合物以增强受试者对抗原的免疫应答的方法。本发明还提供了单独施用 SMIP 化合物或与另一种制剂联合施用 SMIP 化合物以治疗癌症、传染性疾病和/或过敏/哮喘的新型组合物和方法。在另一方面，本发明一般涉及筛选小分子免疫调节组合物的方法。
• An efficient synthesis of pironetins employing a useful chiral building block,(1S,5S,6R)-5-hydroxybicyclo[4.1.0]heptan-2-one
  作者：Hidenori Watanabe、Hiroyuki Watanabe、Masahiko Bando、Masaru Kido、Takeshi Kitahara

  DOI：10.1016/s0040-4020(99)00556-6

  日期：1999.8

  A convergent total synthesis of pironetin 1 and related compound 2 using a chiral building block, (1S,5S,6R)-5-hydroxybicyclo[4.1.0]heptan-2-one 5 is described. Both the dithiane 47 and the epoxide 32 with proper substituents were employed as coupling partners to construct the whole carbon skeleton 48, which was converted to (-)-pironetin 1 and (-)-2 in few steps. The usefulness of 5 for polyketide synthesis was demonstrated. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Total Synthesis of (−)-Pironetin
  作者：Luiz C. Dias、Luciana G. de Oliveira、Márcio A. de Sousa

  DOI：10.1021/ol027211o

  日期：2003.2.1

  [GRAPHICS]The asymmetric total synthesis of pironetin, a compound that shows plant growth regulatory activity, immunosuppressive as well as a remarkable antitumoral activity, is described. The approach involves the use of three very efficient Evans oxazolidinone-mediated syn-aldol condensations, a high-yielding coupling between lithium acetylide ethylenediamine complex and a tosylate followed by methylation, and selective reduction to establish the C12-C13 (E) double bond.
• Identification of the Metabolic Profile of the α-Tubulin-Binding Natural Product (−)–Pironetin
  作者：Sara K. Coulup、David S. Huang、Henry L. Wong、Gunda I. Georg

  DOI：10.1021/acs.jmedchem.8b01774

  日期：2019.2.14

  Pironetin, the only crystallographically confirmed natural product to target a-tubulin, displays potent cytotoxic activity against sensitive and resistant A2780 ovarian cancer cell lines but is only marginally active in vivo. We now report that pironetin has a short half-life (<7 min) in human liver microsomes, suggesting that its limited in vivo efficacy is due to rapid metabolism. Further, we describe the discovery of epoxypironetin as pironetin's major metabolite in human liver microsomes.