desacetylvinflunine hydrazide | 1454288-51-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: desacetylvinflunine hydrazide
• 英文别名: methyl (12S,14S,16R)-16-(1,1-difluoroethyl)-12-[(1R,9R,10S,11R,12R,19R)-12-ethyl-10-(hydrazinecarbonyl)-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-1,10-diazatetracyclo[12.3.1.03,11.04,9]octadeca-3(11),4,6,8-tetraene-12-carboxylate
• CAS: 1454288-51-7
• 化学式: C₄₂H₅₂F₂N₆O₆
• 分子量: 774.908
• InChiKey: JDCADEXYKQHBDA-NJZYMASKSA-N

物化性质

• 密度：
  1.43±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  56
• 可旋转键数：
  7
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  157
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  1H-benzo[d][1,2,3]triazol-1-yl 2-(pyridin-2-yldisulfanyl)ethyl carbonate 、 desacetylvinflunine hydrazide 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以5 mg的产率得到
  参考文献：
  名称：

  Folate–Vinca Alkaloid Conjugates for Cancer Therapy: A Structure–Activity Relationship

  摘要：

  Vintafolide is a potent folate-targeted vinca alkaloid small molecule drug conjugate (SMDC) that has shown promising results in multiple clinical oncology studies. Structurally, vintafolide consists of 4 essential modules: (1) folic acid, (2) a hydrophilic peptide spacer, (3) a disulfide-containing, self-immolative linker, and (4) the cytotoxic drug, desacetylvinblastine hydrazide (DAVLBH). Here, we report a structure-activity study evaluating the biological impact of (i) substituting DAVLBH within the vintafolide molecule with other vinca alkaloid analogues such as vincristine, vindesine, vinflunine, or vinorelbine; (ii) substituting the naturally (S)-configured Asp-Arg-Asp-Asp-Cys peptide with alternative hydrophilic spacers of varied composition; and (iii) varying the composition of the linker module. A series of vinca alkaloid-containing SMDCs were synthesized and purified by HPLC and LCMS. The SMDCs were screened in vitro against folate receptor (FR)-positive cells, and anti-tumor activity was tested against well-established subcutaneous FR-positive tumor xenografts. The cytotoxic and anti-tumor activity was directly compared to that produced by vintafolide. Among all the folate vinca alkaloid SMDCs tested, DAVLBH-containing SMDCs were active, while those constructed with vincristine, vindesine, or vinorelbine analogues failed to produce meaningful biological activity. Within the DAVLBH series, having a bioreleasable, self-immolative linker system was found to be critical for activity since multiple analogues constructed with thioether-based linkers all failed to produce meaningful activity both in vitro and in vivo. Substitutions of some or all of the natural amino acids within vintafolide's hydrophilic spacer module did not significantly change the in vitro or in vivo potency of the SMDCs. Vintafolide remains one of the most potent folate-vinca alkaloid SMDCs produced to date, and continued clinical development is warranted.

  DOI：

  10.1021/bc400441s
• 作为产物：
  描述：

  长春氟宁 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 60.08h， 以52%的产率得到desacetylvinflunine hydrazide
  参考文献：
  名称：

  VINBLASTINE DERIVATIVES, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF

  摘要：

  本发明提供了一种新型的长春碱衍生物，以及其新的应用和制备方法。长春碱衍生物包括水解长春碱和长春碱二肽衍生物。水解长春碱是通过长春碱或其盐与水解水合物反应得到的化合物；而长春碱二肽衍生物是通过水解长春碱与N-苄氧羰基甘氨酸脯氨酸的缩合反应得到的化合物。本发明提供了长春碱衍生物或其药物组合物在抗肿瘤、预防或治疗糖尿病视网膜病变、类风湿性关节炎以及作为血管生成抑制剂或血管破坏剂中的用途。

  公开号：

  US20160068552A1

文献信息

• Vinblastine derivatives, preparation method therefor and application thereof
  申请人：JINAN UNIVERSITY

  公开号：US10377774B2

  公开（公告）日：2019-08-13

  The present invention provides a new kind of vinca alkaloid derivatives, new applications thereof and preparation methods therefor. The vinca alkaloid derivatives comprise hydrazinolyzed vinca alkaloids and vinca alkaloid dipeptide derivative. The hydrazinolyzed vinca alkaloids are the compounds obtained from the reaction of vinca alkaloids or salts thereof with hydrazinolyzed hydrate; and the vinca alkaloid dipeptide derivatives are the compounds obtained from the condensation of hydrazinolyzed vinca alkaloids with N-benzyloxycarbonylglycyl proline. The present invention provides the uses of the vinca alkaloids derivatives or the pharmaceutical compositions thereof in anti-tumor, preventing or treating diabetic retinopathy, rheumatoid arthritis and serving as angiogenesis inhibitors or vascular disrupting agents.

  本发明提供了一种新的长春花生物碱衍生物、其新的应用及其制备方法。长春花生物碱衍生物包括肼解长春花生物碱和长春花生物碱二肽衍生物。肼解长春花生物碱是长春花生物碱或其盐与肼解水合物反应得到的化合物；长春花生物碱二肽衍生物是肼解长春花生物碱与 N-苄氧羰基甘氨酰脯氨酸缩合得到的化合物。本发明提供了长春花生物碱衍生物或其药物组合物在抗肿瘤、预防或治疗糖尿病视网膜病变、类风湿性关节炎以及作为血管生成抑制剂或血管破坏剂中的用途。