isogranulatimide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: isogranulatimide
• 英文别名: 2,4,9,19-tetrazapentacyclo[10.7.0.02,6.07,11.013,18]nonadeca-1(12),3,5,7(11),13,15,17-heptaene-8,10-dione
• 化学式: C₁₅H₈N₄O₂
• 分子量: 276.254
• InChiKey: WXUJAQBSBZLVEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.85
• 重原子数：
  21.0
• 可旋转键数：
  0.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  79.26
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  didemnimide A 在 钯 作用下， 以 硝基苯 为溶剂， 反应 20.0h， 以75%的产率得到isogranulatimide
  参考文献：
  名称：

  Improved Synthesis of Isogranulatimide, a G2 Checkpoint Inhibitor. Syntheses of Didemnimide C, Isodidemnimide A, Neodidemnimide A, 17-Methylgranulatimide, and Isogranulatimides A−C

  摘要：

  A concise, improved synthesis of isogranulatimide (6), a naturally occurring substance with G2 checkpoint inhibition activity, is described. Also reported are the syntheses of didemnimide C (18), isodidemnimide A (24), neodidemnimide A (36), 17-methylgranulatimide (9), and isogranulatimides A (10), B (11), and C (12). Compounds 9-12, congeners of isogranulatimide (6), are now available for biological evaluation.

  DOI：

  10.1021/jo9914723

文献信息

• Granulatimide compounds and uses thereof
  申请人：The University of British Columbia

  公开号：US06291447B1

  公开（公告）日：2001-09-18

  Novel granulatimide compounds and pharmaceutical formulations thereof are provided. Compounds of this invention have the general formula: wherein are independently R or Z as defined below, or in combination F and F′ is Ar1 as defined below; Ar1 is a monocyclic, bicyclic or tricyclic, fully or partially aromatic system containing five or six membered carbocyclic or, oxygen, nitrogen or sulphur containing heterocyclic rings, optionally substituted with R or Z; W is selected from the group consisting of formula (i); (ii) or (iii), wherein the structures are as follows:

  本发明提供了新型的颗粒状酰胺化合物及其制药组合物。该发明的化合物具有以下通式：其中R或Z独立地定义如下，或者F和F'的组合是以下定义的Ar1；Ar1是一个含有五个或六个成员的碳环或含氧、氮或硫杂环的单环、双环或三环、完全或部分芳香性系统，可选地取代R或Z；W从以下公式（i）、（ii）或（iii）的群组中选取，结构如下：
• Differentiation of hepatocyte-like cells from stem cells
  申请人：Agency for Science, Technology and Research

  公开号：US10323228B2

  公开（公告）日：2019-06-18

  Disclosed are methods of differentiating stem cells in order to obtain hepatocyte-like cells, the method comprising the steps of a) subjecting definitive endoderm to at least one epigenetic modulator to obtain hepatoblasts and b) subjecting the hepatoblasts to at least one stem cell differentiation pathway inhibitor to obtain hepatocyte-like cells; wherein steps a) and b) do not comprise the use of a growth factor. In one preferred embodiment, the epigenetic modulator may be sodium butyrate and/or DMSO and the stem cell differentiation pathway inhibitor may be SB431542 and/or DMSO. Also disclosed are hepatocyte-like cells obtained from the method and uses of these cells such as drug screening.

  本发明公开了分化干细胞以获得肝细胞样细胞的方法，该方法包括以下步骤：a)将确定的内胚层置于至少一种表观遗传调节剂中以获得肝母细胞；b)将肝母细胞置于至少一种干细胞分化途径抑制剂中以获得肝细胞样细胞；其中步骤a)和b)不包括使用生长因子。在一个优选的实施方案中，表观遗传调节剂可以是丁酸钠和/或二甲基亚砜，干细胞分化途径抑制剂可以是SB431542和/或二甲基亚砜。还公开了从该方法中获得的肝细胞样细胞以及这些细胞的用途，如药物筛选。
• Granulatimide and Isogranulatimide, Aromatic Alkaloids with G2 Checkpoint Inhibition Activity Isolated from the Brazilian Ascidian <i>Didemnum </i><i>granulatum</i>:  Structure Elucidation and Synthesis
  作者：Roberto G. S. Berlinck、Robert Britton、Edward Piers、Lynette Lim、Michel Roberge、Rosana Moreira da Rocha、Raymond J. Andersen

  DOI：10.1021/jo981607p

  日期：1998.12.1

  Crude methanol ex-tracts of the ascidian Didemum granulatum collected in Brazil showed activity in a new screen for G2 cell cycle checkpoint inhibitors. Bioassay-guided fractionation of the extract yielded the known alkaloids didemnimides A (1) and D (2), the new alkaloid didemnimide E (3), and a new G2 checkpoint inhibitor. Two candidate structures for the inhibitor, named granulatimide (4) and isogranulatimide (5), have been prepared via a short and efficient biomimetic synthesis involving the photolysis of didemnimide A (1). The synthesis revealed that the correct structure for the naturally occurring G2 checkpoint inhibitor is isogranulatimide (5). Granulatimide (4), the other candidate structure, was also found to be a G2 checkpoint inhibitor, and it was subsequently detected in chromatographic fractions associated with purification of D. granulatum alkaloids. Granulatimide (4) and isogranulatimide (5) represent the first examples of a new class of G2 specific cell cycle checkpoint inhibitors and the first ones identified through a rational screening program.
• DIFFERENTIATION OF HEPATOCYTE-LIKE CELLS FROM STEM CELLS
  申请人：Agency for Science, Technology and Research

  公开号：EP3194569A1

  公开（公告）日：2017-07-26
• VALPROIC ACID COMPOUNDS AND WNT AGONISTS FOR TREATING EAR DISORDERS
  申请人：Frequency Therapeutics, Inc.

  公开号：US20220133740A1

  公开（公告）日：2022-05-05

  The present invention provides methods for treating diseases and disorders of the ear with valproic acid compounds and Wnt agonists. The present invention further provides kits for the same.