3-chloro-5H,10H,11H-indolo[3,2-b]quinolin-11-one | 178271-37-9

• 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: 3-chloro-5H,10H,11H-indolo[3,2-b]quinolin-11-one
• 英文别名: 3-chloro-5H-indolo[3,2-b]quinolin-11(10H)-one；3-Chloro-5,10-dihydroindolo[3,2-b]quinolin-11-one
• CAS: 178271-37-9
• 化学式: C₁₅H₉ClN₂O
• 分子量: 268.702
• InChiKey: HKWMNMYPJNMUDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloro-5H,10H,11H-indolo[3,2-b]quinolin-11-one 在 三氯氧磷 作用下， 以66%的产率得到3,11-dichloro-10H-indolo[3,2-b]quinoline
  参考文献：
  名称：

  将基本侧链并入Cryptolepine支架中：结构-抗疟活性关系和机制研究。

  摘要：

  报道了在C-11位上含有基本侧链的隐肾上腺素衍生物的合成及其抗血浆和细胞毒性的评价。丙基，丁基和环烷基二胺侧链显着提高了对耐氯喹的恶性疟原虫的活性与母体化合物相比，可降低细胞毒性。通过荧光显微镜对寄生虫血液阶段进行的定位研究表明，这些衍生物在核内积累，表明掺入碱性侧链不足以促进寄生虫在酸性消化液中的选择性积累。该系列中的大多数化合物都具有与双链DNA双链体以及单体血红素结合的能力，表明这些是与观察到的抗疟活性相关的可能靶标。总体而言，这些具有显着改善的抗疟原虫活性和选择性指数的新型隐氯仿类似物为开发抗药性疟疾寄生虫的有效且高度选择性的药物提供了有希望的起点。

  DOI：

  10.1021/jm101383f
• 作为产物：
  描述：

  4-chloro-2-(2-(phenylamino)acetamido)benzoic acid 在 polyphosphoric acid 作用下， 以36%的产率得到3-chloro-5H,10H,11H-indolo[3,2-b]quinolin-11-one
  参考文献：
  名称：

  将基本侧链并入Cryptolepine支架中：结构-抗疟活性关系和机制研究。

  摘要：

  报道了在C-11位上含有基本侧链的隐肾上腺素衍生物的合成及其抗血浆和细胞毒性的评价。丙基，丁基和环烷基二胺侧链显着提高了对耐氯喹的恶性疟原虫的活性与母体化合物相比，可降低细胞毒性。通过荧光显微镜对寄生虫血液阶段进行的定位研究表明，这些衍生物在核内积累，表明掺入碱性侧链不足以促进寄生虫在酸性消化液中的选择性积累。该系列中的大多数化合物都具有与双链DNA双链体以及单体血红素结合的能力，表明这些是与观察到的抗疟活性相关的可能靶标。总体而言，这些具有显着改善的抗疟原虫活性和选择性指数的新型隐氯仿类似物为开发抗药性疟疾寄生虫的有效且高度选择性的药物提供了有希望的起点。

  DOI：

  10.1021/jm101383f

文献信息

• Bis-alkylamine quindolone derivatives as new antimalarial leads
  作者：João Lavrado、Kaamil Gani、Pedro A. Nobre、Sofia A. Santos、Paula Figueiredo、Dinora Lopes、Virgílio do Rosário、Jiri Gut、Philip J. Rosenthal、Rui Moreira、Alexandra Paulo

  DOI：10.1016/j.bmcl.2010.08.043

  日期：2010.10

  Quindolone derivatives, designed to target the malaria parasite digestive vacuole and heme detoxification pathway, have been synthesized by reaction with 2-chloro-N,N-diethylethanamine. This reaction gave N,O-, N,N- and O-alkylated products containing one or two basic side-chains. The compounds were evaluated for antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum W2 strain and for cytotoxicity in HepG2 A16 hepatic cells. By incorporating alkylamine side chains and chlorine atoms in the quindolone nucleus we transformed the inactive tetracyclic parent quindolones into moderate or highly active and selective antimalarial compounds. The most active and selective compound, 5c, showed an IC50 = 51 nM for P. falciparum and a selectivity ratio of 98. (C) 2010 Elsevier Ltd. All rights reserved.
• Incorporation of Basic Side Chains into Cryptolepine Scaffold: Structure−Antimalarial Activity Relationships and Mechanistic Studies
  作者：João Lavrado、Ghislain G. Cabal、Miguel Prudêncio、Maria M. Mota、Jiri Gut、Philip J. Rosenthal、Cecília Díaz、Rita C. Guedes、Daniel J. V. A. dos Santos、Elena Bichenkova、Kenneth T. Douglas、Rui Moreira、Alexandra Paulo

  DOI：10.1021/jm101383f

  日期：2011.2.10

  The synthesis of cryptolepine derivatives containing basic side-chains at the C-11 position and their evaluations for antiplasmodial and cytotoxicity properties are reported. Propyl, butyl, and cycloalkyl diamine side chains significantly increased activity against chloroquine-resistant Plasmodium falciparum strains while reducing cytotoxicity when compared with the parent compound. Localization studies

  报道了在C-11位上含有基本侧链的隐肾上腺素衍生物的合成及其抗血浆和细胞毒性的评价。丙基，丁基和环烷基二胺侧链显着提高了对耐氯喹的恶性疟原虫的活性与母体化合物相比，可降低细胞毒性。通过荧光显微镜对寄生虫血液阶段进行的定位研究表明，这些衍生物在核内积累，表明掺入碱性侧链不足以促进寄生虫在酸性消化液中的选择性积累。该系列中的大多数化合物都具有与双链DNA双链体以及单体血红素结合的能力，表明这些是与观察到的抗疟活性相关的可能靶标。总体而言，这些具有显着改善的抗疟原虫活性和选择性指数的新型隐氯仿类似物为开发抗药性疟疾寄生虫的有效且高度选择性的药物提供了有希望的起点。
• Bis-alkylamine Indolo[3,2-<i>b</i>]quinolines as Hemozoin Ligands: Implications for Antimalarial Cytostatic and Cytocidal Activities
  作者：Alexandra Paulo、Marta Figueiras、Marta Machado、Catarina Charneira、João Lavrado、Sofia A. Santos、Dinora Lopes、Jiri Gut、Philip J. Rosenthal、Fátima Nogueira、Rui Moreira

  DOI：10.1021/jm500075d

  日期：2014.4.24

  To get insight into the relevance of targeting hemozoin (Hz) crystals, two isomeric series, N5,N10-bis-alkylamine (2a-k) and N10,O11-bis-alkylamine (3a-k) indolo[3,2-b]quinolines, were evaluated for their in vitro activity against chloroquine (CQ)-resistant and sensitive strains of Plasmodium falciparum. In general, compounds of series 3 were more active than isomers 2, with IC50/LD50 ranging from 25/233 nM (3i) to 1.3 (3a)/10.7 (3b) mu M. SAR analyses showed that lipophilicity and chlorine substitution at C3 increased both cytostatic and cytocidal activities. Both series bound to hematin monomer, inhibited beta-hematin formation in vitro, delayed intraerythrocytic parasite development with apparent inhibition of Hz biocrystallization, and showed higher cytocidal activity against schizonts. In addition, cytostatic and cytocidal activities of series 3, but not those of isomers 2, correlated with calculated vacuole accumulation ratios, suggesting different capacities of 2 and 3 to bind to the Hz crystal face 001} exposed on the vacuole aqueous medium and different mechanisms of cytocidal potency.