2-chlorothiazolo[5,4-a]acridin-11(6H)-one | 138962-13-7

• 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: 2-chlorothiazolo[5,4-a]acridin-11(6H)-one
• 英文别名: 2-chloro-6H-[1,3]thiazolo[5,4-a]acridin-11-one
• CAS: 138962-13-7
• 化学式: C₁₄H₇ClN₂OS
• 分子量: 286.741
• InChiKey: GGOQAHLKANOGRI-UHFFFAOYSA-N

物化性质

• 沸点：
  476.7±14.0 °C(Predicted)
• 密度：
  1.530±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 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：
  70.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chlorothiazolo[5,4-a]acridin-11(6H)-one 在 ammonium carbonate 作用下， 以 苯酚 为溶剂， 生成 2-amino[1,3]thiazolo[5,4-a]acridin-11(6H)-one
  参考文献：
  名称：

  DNA-damaging activity and mutagenicity of 16 newly synthesized thiazolo[5,4-a]acridine derivatives with high photo-inducible cytotoxicity

  摘要：

  The discovery of the potent anticancer properties of natural alkaloids in the pyrido-thiazolo-acridine series has suggested that thiazolo-acridine derivatives could be of great interest. In a continuous attempt to develop DNA-binding molecules and DNA photo-cleavers, 16 new thiazolo[5,4a]acridines were synthesized and studied for their photo-inducible DNA-intercalative, cytotoxic and mutagenic activities, by use of the DNA methyl-green bioassay, the Alamar Blue (R) viability assay and the Salmonella mutagenicity test using strains TA97a and TA98 with and without metabolic activation and photo-activation. Without photo-activation, one compound showed a DNA-intercalative activity in the DNA major groove while three compounds displayed intercalating properties after photo-activation. In the dark, four molecules possessed cytotoxic activities against a THP 1 acute monocytic leukemia cell line while 15 derivatives displayed photo-inducible cytotoxic activity against this cell line. All compounds were mutagenic in strain TA97a with metabolic activation (+S9mix) and 15 molecules were mutagenic in strain TA98 without activation (-S9mix). Study of the quantitative structure-activity relationships (QSAR) from the Salmonella mutagenicity data revealed that several descriptors could describe cytotoxic and mutagenic activities after photo-activation. From the results of the mutagenicity test, four compounds with elevated mutagenic activities were selected for additional experiments. Their, capacities to induce single-strand breaks (SSB) and chromosome-damaging effects were monitored by the comet and the micronucleus assays in normal human keratinocytes. Comparison of the minimal genotoxic concentrations showed that two compounds possessed higher capacities to induce SSB after photo-activation. In the micronucleus assay, three molecules were able to induce high numbers of micronuclei following photo-activation. Overall, the results of this study confirm that acridines are predominantly genotoxic via a DNA-intercalating mechanism in the dark, while DNA-adducts were probably induced following photo-activation. (C) 2007 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.mrgentox.2007.10.022
• 作为产物：
  描述：

  邻氯苯甲酸钾 在 硫酸 作用下， 生成 2-chlorothiazolo[5,4-a]acridin-11(6H)-one
  参考文献：
  名称：

  Thiazolo [5,4-α] acridines

  摘要：

  The synthesis of thiazolo [5,4-a] acridines and acridin-9(10H)-ones by cyclisation of anthranilic acids is described. NMR (specially H-1 NMR) was used to ascertain their 'bent' structure.

  DOI：

  10.1016/s0040-4039(00)93582-2

文献信息

• [EN] COMPOUNDS FOR THE TREATMENT OF AMYLOID-ASSOCIATED DISEASES<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DE MALADIES ASSOCIÉES À LA SUBSTANCE AMYLOÏDE
  申请人：REMYND NV

  公开号：WO2016083490A1

  公开（公告）日：2016-06-02

  This invention provides novel compounds of formulae (I) or (II) or a stereoisomer, enantiomer, racemic, or tautomer thereof, (I) (II) wherein the substituents are as defined in the specification. The present invention also relates to the novel compounds for use as a medicine, more in particular for the prevention or treatment of amyloid-related diseases, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, disorders characterized by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such amyloid-related diseases. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds.

  这项发明提供了式(I)或(II)或其立体异构体、对映异构体、消旋体或互变异构体的新化合物，其中取代基如规范中所定义。本发明还涉及用作药物的这些新化合物，更具体地用于预防或治疗与淀粉样蛋白相关的疾病，更具体地说是某些神经系统疾病，如被统称为tau病变的疾病，以及由细胞毒性α-突触核蛋白淀粉生成所特征化的疾病。本发明还涉及利用这些新化合物制备对治疗此类淀粉样蛋白相关疾病有用的药物。本发明还涉及包括这些新化合物的药物组合物以及这些新化合物的制备方法。
• Azido/tetrazole equilibrium in the thiazoloacridinone series
  作者：Jean-Pierre Hanoun、Robert Faure、Jean-Pierre Galy、José Elguero

  DOI：10.1002/jhet.5570330337

  日期：1996.5

  have been prepared for the first time. The azido/tetrazole equilibria of the most soluble compound 4 has been studied in six solvents. The resulting tautomeric equilibrium constants have been compared with those of 2-azido-4,5-dimethylthiazole 1 and 2-azidobenzothiazole 2. The rather insoluble NH derivative 3 when dissolved in DMSO contains 66% of tetrazole 3b while the corresponding anion (obtained

  首次制备了化合物2-叠氮基-6 H-噻唑并[5,4- a ] ac啶酮11-one 3和2-叠氮基-6-丁基噻唑并[5,4 - a ] acridin-11-one 4。已经在六种溶剂中研究了最易溶化合物4的叠氮基/四唑平衡。已将所得的互变异构平衡常数与2-叠氮基-4,5-二甲基噻唑1和2-叠氮基苯并噻唑2比较。当溶于DMSO中时，难溶的NH衍生物3含有66％的四唑3b，而相应的阴离子（通过添加氢化钠获得）全部存在于四唑13b中 形式。
• Robin, Maxime; Faure, Robert; Perichaud, Alain, Heterocycles, 2000, vol. 53, # 2, p. 387 - 395
  作者：Robin, Maxime、Faure, Robert、Perichaud, Alain、Galy, Jean-Pierre

  DOI：——

  日期：——
• Thiazolo [5,4-α] acridines
  作者：Jacques Barbe、Gérard Boyer、Isabelle Carignano、José Elguero、Jean-Pierre Galy、Sandrine Morel、Razika Oughedani

  DOI：10.1016/s0040-4039(00)93582-2

  日期：1991.11

  The synthesis of thiazolo [5,4-a] acridines and acridin-9(10H)-ones by cyclisation of anthranilic acids is described. NMR (specially H-1 NMR) was used to ascertain their 'bent' structure.
• DNA-damaging activity and mutagenicity of 16 newly synthesized thiazolo[5,4-a]acridine derivatives with high photo-inducible cytotoxicity
  作者：Carole Di Giorgio、Anna Nikoyan、Laetitia Decome、Céline Botta、Maxime Robin、Jean-Pierre Reboul、Anne-Sophie Sabatier、Alain Matta、Michel De Méo

  DOI：10.1016/j.mrgentox.2007.10.022

  日期：2008.2

  The discovery of the potent anticancer properties of natural alkaloids in the pyrido-thiazolo-acridine series has suggested that thiazolo-acridine derivatives could be of great interest. In a continuous attempt to develop DNA-binding molecules and DNA photo-cleavers, 16 new thiazolo[5,4a]acridines were synthesized and studied for their photo-inducible DNA-intercalative, cytotoxic and mutagenic activities, by use of the DNA methyl-green bioassay, the Alamar Blue (R) viability assay and the Salmonella mutagenicity test using strains TA97a and TA98 with and without metabolic activation and photo-activation. Without photo-activation, one compound showed a DNA-intercalative activity in the DNA major groove while three compounds displayed intercalating properties after photo-activation. In the dark, four molecules possessed cytotoxic activities against a THP 1 acute monocytic leukemia cell line while 15 derivatives displayed photo-inducible cytotoxic activity against this cell line. All compounds were mutagenic in strain TA97a with metabolic activation (+S9mix) and 15 molecules were mutagenic in strain TA98 without activation (-S9mix). Study of the quantitative structure-activity relationships (QSAR) from the Salmonella mutagenicity data revealed that several descriptors could describe cytotoxic and mutagenic activities after photo-activation. From the results of the mutagenicity test, four compounds with elevated mutagenic activities were selected for additional experiments. Their, capacities to induce single-strand breaks (SSB) and chromosome-damaging effects were monitored by the comet and the micronucleus assays in normal human keratinocytes. Comparison of the minimal genotoxic concentrations showed that two compounds possessed higher capacities to induce SSB after photo-activation. In the micronucleus assay, three molecules were able to induce high numbers of micronuclei following photo-activation. Overall, the results of this study confirm that acridines are predominantly genotoxic via a DNA-intercalating mechanism in the dark, while DNA-adducts were probably induced following photo-activation. (C) 2007 Elsevier B.V. All rights reserved.