(5R,8S,11R)-11-ethenyl-5-methyl-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione | 1056880-65-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (5R,8S,11R)-11-ethenyl-5-methyl-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
• CAS: 1056880-65-9
• 化学式: C₁₉H₂₄N₄O₄S₂
• 分子量: 436.556
• InChiKey: JNRMMKPRYUCMAF-LLJZQGTPSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  S-butyl 3-enyloctanethioate 、 (5R,8S,11R)-11-ethenyl-5-methyl-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以33%的产率得到S-[(E)-4-[(5R,8S,11R)-5-methyl-6,9,13-trioxo-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-enyl] octanethioate
  参考文献：
  名称：

  Synthesis and Activity of Largazole Analogues with Linker and Macrocycle Modification

  摘要：

  To characterize largazole's structural requirements for histone deacetylase (HDAC) inhibitory and anti proliferative activities, a series of analogues with modifications to the side chain or 16-membered macrocycle were prepared and biologically evaluated. Structure-activity relationships suggested that the four-atom linker between the macrocycle and octanoyl group in the side chain and the (S)-configuration at the C17 position are critical to repression of HDAC activity. However, the valine residue in the macrocycle can be replaced with alanine without significant loss of activity.

  DOI：

  10.1021/ol801532s
• 作为产物：
  描述：

  在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 以30 mg的产率得到(5R,8S,11R)-11-ethenyl-5-methyl-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
  参考文献：
  名称：

  Synthesis and Activity of Largazole Analogues with Linker and Macrocycle Modification

  摘要：

  To characterize largazole's structural requirements for histone deacetylase (HDAC) inhibitory and anti proliferative activities, a series of analogues with modifications to the side chain or 16-membered macrocycle were prepared and biologically evaluated. Structure-activity relationships suggested that the four-atom linker between the macrocycle and octanoyl group in the side chain and the (S)-configuration at the C17 position are critical to repression of HDAC activity. However, the valine residue in the macrocycle can be replaced with alanine without significant loss of activity.

  DOI：

  10.1021/ol801532s

文献信息

• Method for preparing largazole analogs and uses thereof
  申请人：Colorado State University Research Foundation

  公开号：US10676504B2

  公开（公告）日：2020-06-09

  Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.

  本文描述了拉加唑的类似物。本文还描述了使用拉加唑和拉加唑类似物治疗癌症和血液疾病的方法，以及包含这些类似物的药物组合物。同样也描述了制备拉加唑类似物的方法。
• Method for Preparing Largazole Analogs and Uses Thereof
  申请人：Colorado State University Research Foundation

  公开号：US20180044376A1

  公开（公告）日：2018-02-15

  Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.