[(13R,14S,18R,19S)-9-hydroxy-16,16-dimethyl-11-oxo-5,7,15,17-tetraoxa-12-azapentacyclo[11.7.0.02,10.04,8.014,18]icosa-1(20),2,4(8),9-tetraen-19-yl] benzoate | 1019642-59-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: [(13R,14S,18R,19S)-9-hydroxy-16,16-dimethyl-11-oxo-5,7,15,17-tetraoxa-12-azapentacyclo[11.7.0.02,10.04,8.014,18]icosa-1(20),2,4(8),9-tetraen-19-yl] benzoate
• CAS: 1019642-59-1
• 化学式: C₂₄H₂₁NO₈
• 分子量: 451.433
• InChiKey: XCARIEPNWCKSNE-IAECCPNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [(13R,14S,18R,19S)-9-hydroxy-16,16-dimethyl-11-oxo-5,7,15,17-tetraoxa-12-azapentacyclo[11.7.0.02,10.04,8.014,18]icosa-1(20),2,4(8),9-tetraen-19-yl] benzoate 在 水 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以60%的产率得到benzoic acid 3,4,7-trihydroxy-6-oxo-2,3,4,4a,5,6-hexahydro[1,3]dioxolo[4,5-j]phenanthridin-2-yl ester
  参考文献：
  名称：

  ISOCARBOSTYRIL ALKALOID DERIVATIVES HAVING ANTI-PROLIFERATIVE AND ANTI-MIGRATORY ACTIVITIES

  摘要：

  揭示了具有抗增殖和抗迁移活性的异喹啉生物碱衍生物。具体来说，公开了符合以下化学式(I)或(II)的化合物，以及其立体异构体、互变异构体、消旋体、前药、代谢物、药学上可接受的盐和/或溶剂，这些化合物在癌症的治疗和预防中很有用。还公开了制备方法。

  公开号：

  US20100076005A1
• 作为产物：
  描述：

  narciclasine-3,4-acetonide 、 苯甲酰氯 在 吡啶 作用下， 以53%的产率得到[(13R,14S,18R,19S)-9-hydroxy-16,16-dimethyl-11-oxo-5,7,15,17-tetraoxa-12-azapentacyclo[11.7.0.02,10.04,8.014,18]icosa-1(20),2,4(8),9-tetraen-19-yl] benzoate
  参考文献：
  名称：

  ISOCARBOSTYRIL ALKALOID DERIVATIVES HAVING ANTI-PROLIFERATIVE AND ANTI-MIGRATORY ACTIVITIES

  摘要：

  揭示了具有抗增殖和抗迁移活性的异喹啉生物碱衍生物。具体来说，公开了符合以下化学式(I)或(II)的化合物，以及其立体异构体、互变异构体、消旋体、前药、代谢物、药学上可接受的盐和/或溶剂，这些化合物在癌症的治疗和预防中很有用。还公开了制备方法。

  公开号：

  US20100076005A1

文献信息

• ISOCARBOSTYRIL ALKALOID DERIVATIVES HAVING ANTI-PROLIFERATIVE AND ANTI-MIGRATORY ACTIVITIES
  申请人：Ingrassia Laurent

  公开号：US20100076005A1

  公开（公告）日：2010-03-25

  Isocarbostyril alkaloid derivatives having an anti-proliferative and anti-migratory activities are disclosed. In particular, compounds of formula (I) or (II), as well as stereoisomers, tautomers, racemates, prodrugs, metabolites thereof, pharmaceutically acceptable salt and/or solvate are encompassed which are useful in the treatment and prophylaxis of cancer. Methods of preparation are also disclosed.

  揭示了具有抗增殖和抗迁移活性的异喹啉生物碱衍生物。具体来说，公开了符合以下化学式(I)或(II)的化合物，以及其立体异构体、互变异构体、消旋体、前药、代谢物、药学上可接受的盐和/或溶剂，这些化合物在癌症的治疗和预防中很有用。还公开了制备方法。
• [EN] NEW ISOCARBOSTYRIL ALKALOID DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'ISOCARBOSTYRYL ALCALOÏDE
  申请人：UNIBIOSCREEN SA

  公开号：WO2008043846A2

  公开（公告）日：2008-04-17

  [EN] The present invention relates to novel isocarbostyril alkaloid derivatives having an anti-proliferative and anti-migratory activities, in particular to compounds of formula (I) or (II), stereoisomers, tautomers, racemates, prodrugs, metabolites thereof, or a pharmaceutically acceptable salt and/or solvate thereof, wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ have the same meaning as that defined in the claims. The present invention also relates to a method for the preparation of said compounds, to compositions, in particular pharmaceuticals, comprising such compounds, and to uses of such compounds in the treatment and prophylaxis of cancer.
  [FR] La présente invention concerne de nouveaux dérivés d'isocarbostyryl alcaloïde présentant des activités antiprolifératives et anti-migratoires, en particulier des composés représentés par la formule (I) ou (II), des stéréo-isomères, des tautomères, des racémates, des promédicaments, des métabolites de ceux-ci, ou un sel et/ou un solvate de ceux-ci acceptable du point de vue pharmaceutique, où R¹, R², R³, R⁴, R⁵, R⁶, et R⁷ ont la même signification que celle qui est définie dans les revendications. La présente invention porte également sur un procédé pour la préparation desdits composés, sur des compositions, en particulier des compositions pharmaceutiques comportant de tels composés, et sur des utilisations de tels composés dans le traitement et la prophylaxie du cancer.
• Structure−Activity Relationship Analysis of Novel Derivatives of Narciclasine (an <i>Amaryllidaceae</i> Isocarbostyril Derivative) as Potential Anticancer Agents
  作者：Laurent Ingrassia、Florence Lefranc、Janique Dewelle、Laurent Pottier、Véronique Mathieu、Sabine Spiegl-Kreinecker、Sébastien Sauvage、Mohamed El Yazidi、Mischaël Dehoux、Walter Berger、Eric Van Quaquebeke、Robert Kiss

  DOI：10.1021/jm8013585

  日期：2009.2.26

  Narciclasine (1) is a plant growth regulator that has been previously demonstrated to be proapoptotic to cancer cells at high concentrations (>= 1 mu M). Data generated in the present study show that narciclasine displays potent antitumor effects in apoptosis-resistant as well as in apoptosis-sensitive cancer cells by impairing the organization of the actin cytoskeleton in cancer cells at concentrations that are not cytotoxic (IC50 values of 30-90 nM). The current study further revealed that any chemical modification to the narciclasine backbone generally led to compounds of variable stability, weaker activity, or even the complete loss of antiproliferative effects in vitro. However, one hemisynthetic derivative of narciclasine, compound 7k, demonstrated by both the intravenous and oral routes higher in vivo antitumor activity in human orthotopic 4, glioma models in mice when compared to narciclasine at nontoxic doses. Narciclasine and compound 7k may therefore be of potential use to combat brain tumors.