9-chloro-6,7-dimethoxy-1,2,3,4-tetrahydroacridine | 187960-36-7

• 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: 9-chloro-6,7-dimethoxy-1,2,3,4-tetrahydroacridine
• CAS: 187960-36-7
• 化学式: C₁₅H₁₆ClNO₂
• mdl: MFCD16383552
• 分子量: 277.751
• InChiKey: MXDIXRMGTOVJKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-chloro-6,7-dimethoxy-1,2,3,4-tetrahydroacridine 在 氨 、 苯酚 作用下， 反应 4.0h， 以90%的产率得到6,7-Dimethoxy-1,2,3,4-tetrahydro-acridin-9-ylamine
  参考文献：
  名称：

  Del Giudice; Borioni; Mustazza, Il Farmaco, 1996, vol. 51, # 11, p. 693 - 698

  摘要：

  DOI：
• 作为产物：
  描述：

  2-环己酮甲酸乙酯 在 对甲苯磺酸 、 三氯氧磷 作用下， 以 二苯醚 、 甲苯 为溶剂， 反应 9.5h， 生成 9-chloro-6,7-dimethoxy-1,2,3,4-tetrahydroacridine
  参考文献：
  名称：

  Del Giudice; Borioni; Mustazza, Il Farmaco, 1996, vol. 51, # 11, p. 693 - 698

  摘要：

  DOI：

文献信息

• [EN] TRICYCLIC COMPOUNDS AS HISTONE METHYL-TRANSFERASE INHIBITORS<br/>[FR] COMPOSÉS TRICYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS D'HISTONE MÉTHYLTRANSFÉRASES
  申请人：GLOBAL BLOOD THERAPEUTICS INC

  公开号：WO2019036377A1

  公开（公告）日：2019-02-21

  The present disclosure provides certain tricyclic compounds that are histone methyltransferases G9a and/or GLP inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of G9a and/or GLP such as cancers and hemoglobinopathies (e.g., beta-thalassemia and sickle cell disease). Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本公开提供了某些三环化合物，它们是组蛋白甲基转移酶G9a和/或GLP抑制剂，因此可用于治疗通过抑制G9a和/或GLP可治疗的疾病，如癌症和血红蛋白病（例如β地中海贫血和镰状细胞病）。还提供了含有这些化合物的药物组合物和制备这些化合物的方法。
• [EN] ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 INHIBITORS,COMPOSITIONS AND USES THEREOF<br/>[FR] INHIBITEURS D'ECTONUCLÉOTIDE PYROPHOSPHATASE-PHOSPHODIESTÉRASE 1, COMPOSITIONS ET UTILISATIONS DE CEUX-CI
  申请人：BETTA PHARMACEUTICALS CO LTD

  公开号：WO2021203772A1

  公开（公告）日：2021-10-14

  The present invention relates to compounds of Formula (I), methods of using the compounds as ENPP1 inhibitors, and pharmaceutical compositions comprising such compounds.The compounds are useful in treating cancers and infectious diseases.

  本发明涉及式（I）化合物，使用这些化合物作为ENPP1抑制剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗癌症和传染性疾病方面是有用的。
• Synthesis, biological evaluation, and molecular modeling simulations of new heterocyclic hybrids as multi-targeted anti-Alzheimer's agents
  作者：Omnia M. Waly、Kareem M. Saad、Hussein I. El-Subbagh、Said M. Bayomi、Mariam A. Ghaly

  DOI：10.1016/j.ejmech.2022.114152

  日期：2022.3

  the multifactorial nature of Alzheimer disease (AD) increased the demands for multi-targeted directed ligands (MTDLs) to overcome possible drug-drug interactions of the combination therapy, and to acquire superior therapeutic profile than single targeted molecules. Two main scaffolds namely: pyrazolopyridine and tetrahydroacridine (THA) were used to synthesize four different series of integrated multi-targeted

  阿尔茨海默病 (AD) 的广泛性和对多因素性质的认识增加了对多靶向定向配体 (MTDL) 的需求，以克服联合疗法可能的药物-药物相互作用，并获得比单一靶向分子更好的治疗效果。两个主要支架，即：吡唑并吡啶和四氢吖啶（THA）用于合成四种不同系列的具有ChE（h AChE或h BuChE）、Aβ1-42的综合多靶点合成子除了最佳的金属螯合能力外，还具有聚集抑制能力。对他克林的 THA 核心的 9-氨基功能进行结构修饰，吡唑并吡啶支架直接与多种环状仲胺连接或使用酰胺间隔物或乙胺桥或使 THA 与吡唑并吡啶接合以产生杂化化合物。不同的 9-氨基取代提高了7-或 6,7-二取代 THA 衍生物的体外 h AChE 活性。化合物16和28被证明是多模式抗 AD 剂，因为它们是有效的此外，AChE 抑制剂可以与外周阴离子位点 (PAS) 的氨基酸结合，从而影响 Aβ 聚集，从而影响 Aβ 依赖性神经毒性
• Optimization of 1,2,3,4-Tetrahydroacridin-9(10<i>H</i>)-ones as Antimalarials Utilizing Structure–Activity and Structure–Property Relationships
  作者：R. Matthew Cross、Jordany R. Maignan、Tina S. Mutka、Lisa Luong、Justin Sargent、Dennis E. Kyle、Roman Manetsch

  DOI：10.1021/jm200015a

  日期：2011.7.14

  Antimalarial activity of 1,2,3,4-tetrahydroacridin-9(10H)-ones (THAs) has been known since the 1940s and has garnered more attention with the development of the acridinedione floxacrine (1) in the 1970s and analogues thereof such as WR 243251 (2a) in the 1990s. These compounds failed just prior to clinical development because of suboptimal activity, poor solubility, and rapid induction of parasite resistance. Moreover, detailed structure-activity relationship (SAR) studies of the THA core scaffold were lacking and SPR studies were nonexistent. To improve upon initial findings, several series of 1,2,3,4-tetrahydroacridin-9(10H)-ones were synthesized and tested in a systematic fashion, examining each compound for antimalarial activity, solubility, and permeability. Furthermore, a select set of compounds was chosen for microsomal stability testing to identify physicochemical liabilities of the THA scaffold. Several potent compounds (EC50 < 100 nM) were identified to be active against the clinically relevant isolates W2 and TM90-C2B while possessing good physicochemical properties and little to no cross-resistance.
• TRICYCLIC COMPOUNDS AS HISTONE METHYL-TRANSFERASE INHIBITORS
  申请人：Global Blood Therapeutics, Inc.

  公开号：EP3668863A1

  公开（公告）日：2020-06-24