5-deoxy L-783277 | 1255639-70-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: 5-deoxy L-783277
• 英文别名: (3S,5Z,9S)a9,16aDihydroxya14amethoxya3amethyla3,4,7,8,9,10,11,12aoctahydroa1Ha2abenzoxacyclotetradecinea1,7adione；(4S,6Z,10S)-10,18-dihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,15,17-tetraene-2,8-dione
• CAS: 1255639-70-3
• 化学式: C₁₉H₂₄O₆
• 分子量: 348.396
• InChiKey: QMEZKJBCLUGJTN-APQFZBCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-1-(tert-butyldimethylsiloxy)-3-(tert-butyldiphenylsiloxy)hex-5-ene 在 咪唑 、 甲醇 、 potassium fluoride 、 Jones reagent 、 正丁基锂 、 草酰氯 、 水 、 氢气 、 对甲苯磺酸 、 氟化氢吡啶 、 二甲基亚砜 、 9-硼双环[3.3.1]壬烷 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， -78.0~87.0 ℃ 、750.01 kPa 条件下， 反应 82.83h， 生成 5-deoxy L-783277
  参考文献：
  名称：

  Kinase Inhibition by Deoxy Analogues of the Resorcylic Lactone L-783277

  摘要：

  The natural product L-783277 is a resorcylic lactone type covalent kinase inhibitor We prepared the 5'-deoxy analogue of L-783277 (1) in a stereoselective fashion. Remarkably, this analogue retains almost the full kinase inhibitory potential of natural L-783277, with low nanomolar IC50 values against the most sensitive kinases, and it exhibits essentially the same selectivity profile (within the panel of 39 kinases investigated). In contrast, removal of both the 4'- and the 5'-hydroxyl groups leads to a more significant reduction in kinase inhibitory activity and so does a change in the geometry of the C7'-C8' double bond in 1 from Z to E. These findings offer new perspectives for the design of second generation resorcylic lactone-based kinase inhibitors.

  DOI：

  10.1021/ml1001807

文献信息

• RESORCYLIC ACID LACTONE COMPOUNDS
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20140155635A1

  公开（公告）日：2014-06-05

  Disclosed are a novel resorcyclic acid lactone compound with inhibitory activity against protein kinases, a pharmaceutically acceptable salt thereof, a method for the synthesis thereof, and a pharmaceutical composition for the treatment and prevention of various cancer diseases comprising the same as an active ingredient. The novel resorcyclic acid lactone compound is useful as a therapeutic for cancer diseases, especially blood cancer, inter alia, acute myeloid leukemia (AML).

  公开了一种新型对蛋白激酶具有抑制活性的蒽环酸内酯化合物，其药用可接受盐，合成方法以及包含该化合物作为活性成分的治疗和预防各种癌症疾病的药物组合物。这种新型蒽环酸内酯化合物可用作治疗癌症疾病的药物，特别是血癌，例如急性髓细胞白血病（AML）。
• Kinase Inhibition by Deoxy Analogues of the Resorcylic Lactone L-783277
  作者：Marc Liniger、Christian Neuhaus、Tatjana Hofmann、Luca Fransioli-Ignazio、Michel Jordi、Peter Drueckes、Jörg Trappe、Doriano Fabbro、Karl-Heinz Altmann

  DOI：10.1021/ml1001807

  日期：2011.1.13

  The natural product L-783277 is a resorcylic lactone type covalent kinase inhibitor We prepared the 5'-deoxy analogue of L-783277 (1) in a stereoselective fashion. Remarkably, this analogue retains almost the full kinase inhibitory potential of natural L-783277, with low nanomolar IC50 values against the most sensitive kinases, and it exhibits essentially the same selectivity profile (within the panel of 39 kinases investigated). In contrast, removal of both the 4'- and the 5'-hydroxyl groups leads to a more significant reduction in kinase inhibitory activity and so does a change in the geometry of the C7'-C8' double bond in 1 from Z to E. These findings offer new perspectives for the design of second generation resorcylic lactone-based kinase inhibitors.