6-bromo-2-chloro-3-iodoquinoline | 916429-26-0

• 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: 6-bromo-2-chloro-3-iodoquinoline
• 英文别名: 6-Bromo-2-chloro-3-iodoquinoline
• CAS: 916429-26-0
• 化学式: C₉H₄BrClIN
• 分子量: 368.399
• InChiKey: QMOWQGDNWJIGAV-UHFFFAOYSA-N

物化性质

• 沸点：
  403.9±40.0 °C(Predicted)
• 密度：
  2.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-bromo-2-chloro-3-iodoquinoline 在 溶剂黄146 作用下， 以90%的产率得到6-bromo-3-iodoquinolinone
  参考文献：
  名称：

  Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors

  摘要：

  Through a comparison of X-ray co-crystallographic data for 1 and 2 in the Chek1 active site, it was hypothesized that the affinity of the indolylquinolinone series (2) for Chek1 kinase would be improved via C6 substitution into the hydrophobic region I (HI) pocket. An efficient route to 6-bromo-3-indolyl-quinolinone (9) was developed, and this series was rapidly optimized for potency by modification at C6. A general trend was observed among these low nanomolar Chek1 inhibitors that compounds with multiple basic amines, or elevated polar surface area (PSA) exhibited poor cell potency. Minimization of these parameters (basic amines, PSA) resulted in Chek1 inhibitors with improved cell potency, and preliminary pharmacokinetic data are presented for several of these compounds.

  DOI：

  10.1016/j.bmcl.2006.08.053
• 作为产物：
  描述：

  4 -溴- 2 - 碘苯甲胺 在 N-甲基吡咯烷酮 、 palladium diacetate 、 三正丁胺 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 乙二醇 为溶剂， 反应 0.33h， 生成 6-bromo-2-chloro-3-iodoquinoline
  参考文献：
  名称：

  Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors

  摘要：

  Through a comparison of X-ray co-crystallographic data for 1 and 2 in the Chek1 active site, it was hypothesized that the affinity of the indolylquinolinone series (2) for Chek1 kinase would be improved via C6 substitution into the hydrophobic region I (HI) pocket. An efficient route to 6-bromo-3-indolyl-quinolinone (9) was developed, and this series was rapidly optimized for potency by modification at C6. A general trend was observed among these low nanomolar Chek1 inhibitors that compounds with multiple basic amines, or elevated polar surface area (PSA) exhibited poor cell potency. Minimization of these parameters (basic amines, PSA) resulted in Chek1 inhibitors with improved cell potency, and preliminary pharmacokinetic data are presented for several of these compounds.

  DOI：

  10.1016/j.bmcl.2006.08.053

文献信息

• [EN] FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR 1<br/>[FR] DÉRIVÉS DE 1,4-DIHYDRODIOXINE FUSIONNÉS À UTILISER EN TANT QU'INHIBITEURS DE FACTEUR DE TRANSCRIPTION 1 DU CHOC THERMIQUE
  申请人：CANCER REC TECH LTD

  公开号：WO2015049535A1

  公开（公告）日：2015-04-09

  The present invention relates to compounds of formula I wherein A1, A2 R4 and Q are as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式I的化合物，其中A1、A2、R4和Q如本文所定义。本发明的化合物是热休克因子1（HSF1）的抑制剂。具体来说，本发明涉及将这些化合物用作治疗和/或预防增殖性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的方法，以及包含它们的药物组合物。
• [EN] AMINO HETEROARYL COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE<br/>[FR] COMPOSÉS D'AMINOHÉTÉROARYLE EN TANT QUE MODULATEURS DE BÊTA-SÉCRÉTASE ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2011090911A1

  公开（公告）日：2011-07-28

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula (I); wherein ring A, B1, B2, B3, L, R1, R2, ring Z, m and n of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula (I), intermediates and processes useful for the preparation of compounds of Formula (I).

  本发明涉及一类新的化合物，用于调节β-分泌酶酶活性，并用于治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）及相关疾病。在一种实施例中，这些化合物具有一般的化学式（I）；其中化合物式（I）中的环A、B1、B2、B3、L、R1、R2、环Z、m和n在此处定义。该发明还包括将这些化合物用于制备用于治疗与β-分泌酶蛋白活性相关的疾病和症状的药物组合物，包括阿尔茨海默病（AD）、认知缺陷、认知损害、精神分裂症和其他与大脑斑块的形成和/或沉积相关和/或由此引起的中枢神经系统疾病。该发明还涉及化合物式（I）的进一步实施例、中间体和用于制备化合物式（I）的有用过程。
• Structural Simplification of Bedaquiline: the Discovery of 3-(4-(<i>N</i>,<i>N</i>-Dimethylaminomethyl)phenyl)quinoline-Derived Antitubercular Lead Compounds
  作者：Chunxian He、Laura Preiss、Bin Wang、Lei Fu、Hui Wen、Xiang Zhang、Huaqing Cui、Thomas Meier、Dali Yin

  DOI：10.1002/cmdc.201600441

  日期：2017.1.20

  their potent antitubercular activity at sub‐microgram per mL concentrations against both sensitive and multidrug‐resistant (MDR) Mycobacterium tuberculosis strains. Six out of the top nine MIC‐ranked candidates were found to inhibit mycobacterial ATP synthesis activity with IC50 values between 20 and 40 μm, one had IC50>66 μm, and two showed no inhibition, despite their antitubercular activity. These results

  Bedaquiline（BDQ）是一种新型的高效抗结核药物，已于2013年获得美国FDA批准。由于立体结构的复杂性，化学合成和化合物优化非常困难且昂贵。这项研究描述了苯达喹啉的结构简化，同时保留了抗结核活性。该化合物的结构被分为多个片段，并以各种组合重新组装，同时用非手性键取代了两个手性碳原子。设计了四个系列的类似物。这些候选药物对敏感和耐多药（MDR）结核分枝杆菌均保持其有效的抗结核活性，浓度为每微克每毫升。株。六出前的被发现有9 MIC-排名候选抑制分枝杆菌ATP合成与IC活性50 20和40μ之间的值米，一个有IC 50 > 66μ米，和两个显示无抑制，尽管它们抗结核活性。这些结果为开发化学上不太复杂，成本更低的苯达喹啉衍生物提供了基础，并描述了对非ATP合酶相关靶标具有抗结核活性的两种衍生物的鉴定。
• 一类喹啉类衍生物、其制备方法和用途
  申请人：中国医学科学院药物研究所

  公开号：CN106167464A

  公开（公告）日：2016-11-30

  本发明公开了一类新的如下结构通式(I)所示的喹啉类衍生物、其制备方法，含有它们的药物组合物，及其作为抗结核药物的用途。本发明还涉及其生理上可接受的无机酸或有机酸所组成的盐、N‑氧化物；这类化合物具有优良的抗结核活性，可作为结核病包括多药耐药结核病的治疗用药。
• Amino Heteroaryl Compounds as Beta-Secretase Modulators and Methods of Use
  申请人：Paras Nick A.

  公开号：US20130040931A1

  公开（公告）日：2013-02-14

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula (I); wherein ring A, B 1 , B 2 , B 3 , L, R 1 , R 2 , ring Z, m and n of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula (I), intermediates and processes useful for the preparation of compounds of Formula (I).

  本发明涉及一种新的化合物类别，用于调节Beta-分泌酶酶活性和治疗Beta-分泌酶介导的疾病，包括阿尔茨海默病（AD）和相关病症。在一种实施例中，所述化合物具有通式（I）；其中，通式I中的环A、B1、B2、B3、L、R1、R2、环Z、m和n定义如下。本发明还包括将这些化合物用于制备治疗、预防或治疗与Beta-分泌酶蛋白活性相关的疾病和病症的药物组合物。这些疾病包括阿尔茨海默病（AD）、认知缺陷、认知障碍、精神分裂症和其他与大脑斑块形成和/或沉积相关和/或由此引起的中枢神经系统疾病。本发明还包括通式（I）的进一步实施例、中间体和用于制备通式（I）化合物的方法。