ascididemin | 114622-04-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ascididemin
• 英文别名: 9H-quino[4,3,2-de][1,10]phenanthrolin-9-one；ascididemine；2,12,15-triazapentacyclo[11.7.1.03,8.09,21.014,19]henicosa-1,3,5,7,9(21),10,12,14(19),15,17-decaen-20-one
• CAS: 114622-04-7
• 化学式: C₁₈H₉N₃O
• 分子量: 283.289
• InChiKey: BTAIBIXHXSXUFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ascididemin 在 溴 、 溶剂黄146 作用下， 反应 24.0h， 以86%的产率得到6-Bromo-2,12,15-triazapentacyclo[11.7.1.03,8.09,21.014,19]henicosa-1(21),2,4,6,8,10,12,14(19),15,17-decaen-20-one
  参考文献：
  名称：

  Synthesis and In Vitro Antitumor Activity of Novel Ring D Analogues of the Marine Pyridoacridine Ascididemin: Structure−Activity Relationship

  摘要：

  Marine compounds with pyridoacridine skeletons are known to exhibit interesting antitumor activities. Ascididemin has already been reported as displaying significant antitumor activities in vitro and has also been found to have a relatively high global toxicity in vivo. We synthesized a series of 16 analogues (among which 11 compounds were different from previously described ones) with the aim of developing new anticancer agents with significant improved efficacy/tolerability ratios. These compounds were obtained either by total synthesis from 5,8-quinolinedione and substituted 2-aminoacetophenones or by the direct substitution of ascididemin. The different compounds and ascididemin used as the control compound were tested at six different concentrations on 12 different human cancer cell lines of various histopathological types (glioblastomas and breast, colon, lung, prostate, and bladder cancers). The IC50 value (ie., the drug concentration inhibiting the mean growth value of the 12 cell lines by 50%) of these compounds ranged over five log concentrations, i.e., between 10 000 and 0.1 nM. For several new chemical entities, the antitumor activity (determined in vitro) and tolerability (determined in vivo) were superior to those of the parent alkaloids, i.e., ascididemin and 2-bromoleptoclinidone.

  DOI：

  10.1021/jm0208774
• 作为产物：
  描述：

  5-硝基-8-羟基喹啉 在 iron(III) sulfate 、 cerium(III) chloride heptahydrate 、 硫酸 、 氧气 、 sodium hydrogensulfite 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 27.0h， 生成 ascididemin
  参考文献：
  名称：

  G-四链体和双链体DNA结合研究新型含有Ascdidemin配体的钌（II）配合物。

  摘要：

  本文合成并表征了三种新的以Ascididemin（ASC）为主要配体的钌（II）聚吡啶基配合物。它们与不同的G-四链体（Htelo，c-myc和c-kit）（Htelo：人类端粒DNA，c-myc：细胞-骨髓细胞瘤病病毒癌基因，c-kit：癌基因c-kit启动子序列）和双链体（ds26的相互作用） ）通过一系列光谱技术，包括紫外线-可见（紫外可见）光谱，FID（荧光嵌入剂置换）测定法和FRET（荧光共振能量转移）融解测定法，对游离序列ASC的DNA序列进行了比较研究。还进行了分子对接研究以支持化合物与G-四链体DNA的结合模式。结果表明[Ru（bpy）2 ASC]·（PF 6）2（1），[Ru（phen）2 ASC]·（PF 6）2（2），[Ru（tatp）2 ASC]·（PF 6）2（3）（bpy = 2,2'-联吡啶， phen = 1,10-菲咯啉，tatp = 1,4,8,9-四氮

  DOI：

  10.1016/j.jinorgbio.2019.03.021

文献信息

• [EN] ANTICANCER CONJUGATE<br/>[FR] CONJUGUÉ ANTICANCÉREUX
  申请人：ADAMED SP ZOO

  公开号：WO2014141094A1

  公开（公告）日：2014-09-18

  An anticancer conjugate, which comprises a fusion protein comprising domain (a), which is the functional fragment of a sequence of soluble human TRAIL (hTRAIL) protein beginning with an amino acid at a position not lower than hTRAIL95 or a sequence having at least 70% identity with said functional fragment, domain (b) which is the sequence of an effector peptide having proapoptotic, antiangiogenic, antiproliferative or pore forming activity, and conjugation domain (d) for attachment of a chemical compound selected from the group consisting of the sequences Cys Ala Ala Ala Cys Ala Ala Cys and Cys Ala Ala Cys Ala Ala Ala Cys, and a molecule of a chemical compound Z having antiblastic activity, which is attached to said conjugation domain (d) of said fusion protein directly or via a conjugation linker L.

  一种抗癌结合物，包括融合蛋白，该融合蛋白包括以下部分：（a）功能性片段，该片段是以不低于hTRAIL95位置的氨基酸开始的可溶性人类TRAIL（hTRAIL）蛋白序列的片段，或者具有与该功能性片段至少70%同源性的序列；（b）是具有促凋亡、抗血管生成、抗增殖或形成孔活性的效应肽序列；以及（d）用于连接来自以下序列的化学化合物的结合结构域，该序列包括Cys Ala Ala Ala Cys Ala Ala Cys和Cys Ala Ala Cys Ala Ala Ala Cys，以及具有抗肿瘤活性的化学化合物Z的分子，该分子附着在所述融合蛋白的结合结构域（d）上，直接或通过结合连接物L连接。
• Synthesis of Ascididemine and an Isomer
  作者：Mercedes Álvarez、Lidia Feliu、Wadi Ajana、John A. Joule、José Luis Fernández-Puentes

  DOI：10.1002/(sici)1099-0690(200003)2000:5<849::aid-ejoc849>3.0.co;2-r

  日期：2000.3

  Ascididemine (9H-quino[4,3,2-de][1,10]phenanthrolin-9-one) (1) and an isomer (9H-quino[4,3,2-de][1,7]phenanthrolin-9-one) (4) have been synthesized starting from 1,4-dimethoxyacridone (7). The acridone was converted into 1,4-dimethoxy-9-ethynylacridine (11) by a triflate coupling. The ethynylacridine was converted in one-pot into 3H-6-methoxypyrido[2,3,4-kl]acridine (15) by reaction with sodium diformylamide;

  Ascididemine (9H-quino[4,3,2-de][1,10]phenanthrolin-9-one) (1) 和异构体 (9H-quino[4,3,2-de][1,7]phenanthrolin -9-one) (4) 已从 1,4-二甲氧基吖啶酮 (7) 开始合成。通过三氟甲磺酸酯偶联，吖啶酮被转化为 1,4-二甲氧基-9-乙炔基吖啶 (11)。通过与二甲酰胺钠反应，乙炔丙啶在一锅中转化为3H-6-甲氧基吡啶并[2,3,4-kl]吖啶(15)；讨论了这种关键转变的机制。转化为 6H-4-溴吡啶并[2,3,4-kl]吖啶-6-酮 (19) 和 6H-吡啶并[2,3,4-kl]吖啶-6-酮 (17)，然后反应这些中的每一个在高压条件下与丙烯醛N，N-二甲基腙，分别得到ascididemine及其异构体。
• Intramolecular Michael-type addition of azadienes to 1,4-naphthoquinones instead of Aza-Diels–Alder cycloaddition: a synthesis of ascididemin
  作者：Juan M. Cuerva、Diego J. Cárdenas、Antonio M. Echavarren

  DOI：10.1039/b202555h

  日期：2002.5.23

  α,β-Unsaturated hydrazones tethered by an amino group to 1,4-naphthoquinone or quinoline-5,8-dione do not react by intramolecular aza-Diels–Alder cycloaddition. Instead, these substrates cyclize to form benzo[b]acridine-6,11-dione or pyrido[2,3-b]acridine-5,12-dione derivatives, respectively. This route leads to a highly concise synthesis of the pyridoacridine alkaloid ascididemin.

  与氨基连接的α,β-不饱和肼酮与1,4-萘醌或喹啉-5,8-二酮并不会通过分子内氮杂Diels–Alder环加成反应。相反，这些底物会环化形成苯并[b]氨基芴-6,11-二酮或吡啶[2,3-b]氨基芴-5,12-二酮衍生物。该路线实现了吡啶氨基芴生物碱ascididemin的高效合成。
• New synthesis of pyridoacridines based on an intramolecular aza-Diels–Alder reaction followed by an unprecedented rearrangement†
  作者：Juan M. Cuerva、Diego J. Cárdenas、Antonio M. Echavarren

  DOI：10.1039/a905234h

  日期：——

  The synthesis of pyridoacridines related to the ascididemins can be performed by an intramolecular aza-Diels–Alder cycloaddition of an α,β-unsaturated hydrazone to a quinone followed by an unprecedented rearrangement to yield benzo- or pyrido-[b]acridine-6,11-diones.

  通过δ,δ-不饱和腙与醌的分子内偶氮-DielsâAlder 环加成反应，然后进行前所未有的重排，生成苯并吖啶或吡啶并[b]吖啶-6,11-二酮，从而合成与抗坏血酸有关的吡啶并吖啶。
• Total Synthesis of Ascididemin-Type Alkaloids Using Alkyne Building Blocks
  作者：Hao Yin、Naiyu Shan、Shaozhong Wang、Zhu-Jun Yao

  DOI：10.1021/jo501927e

  日期：2014.10.17

  ascididemin, bromoleptoclinidinone, neocalliactine acetate, and 11-hydroxyascididemin, based on a Brønsted acid-promoted tandem annulation has been developed. Alkyne building blocks were first designed and then employed in alkaloid synthesis; these building blocks can be accessed by a Sonogashira coupling reaction on a multigram scale.

  已经开发了一种基于布朗斯台德酸促进的串联环化技术的常见的杀虫剂型生物碱方法，包括杀虫剂，溴代肽环己酮，乙酸新愈伤组织乙酸酯和11-羟基杀虫剂。首先设计炔烃构建基块，然后将其用于生物碱合成。这些构建基块可以通过数克规模的Sonogashira偶联反应访问。