6-chloroquinoline-3,4-diamine | 110643-78-2

• 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-chloroquinoline-3,4-diamine
• CAS: 110643-78-2
• 化学式: C₉H₈ClN₃
• 分子量: 193.636
• InChiKey: JSWSNMRGRLUNDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 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：
  64.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloroquinoline-3,4-diamine 在 sodium pyrosulfate 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 4,8-dichloro-2-(2-chlorophenyl)imidazo[4,5-c]quinoline
  参考文献：
  名称：

  7-Phenyl-imidazoquinolin-4(5H)-one derivatives as selective and orally available mPGES-1 inhibitors

  摘要：

  To identify compounds with strong mPGES-1 inhibitory activity and clear in vitro ADME profile, we optimized the lead compound 1 by carrying our substitutions at the C(7)-and C(8)-positions. Replacement of the bromine atom of 1 with various substituents led to identification of the phenyl group as the best C(7)-substituent giving strong inhibitory activity with good in vitro ADME profile. Further SAR examination on both the C(2)-and the C(7)-phenyl groups provided compound 39 as the best candidate for further development. Compound 39 exhibited strong mPGES-1 inhibitory activity (IC50 = 4.1 nM), potent cell-based functional activity (IC50 = 33 nM) with good mPGES-1 selectivity (over 700-fold), excellent in vitro ADME profile, and good oral absorption in rat PK study. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.069
• 作为产物：
  描述：

  4,6-二氯-3-硝基喹啉 在 sodium dithionite 、 氨 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 4.0h， 生成 6-chloroquinoline-3,4-diamine
  参考文献：
  名称：

  三唑并 [1,5-c] 喹唑啉作为一流骨形态发生蛋白放大器化学型的表型发现

  摘要：

  表型药物发现 (PDD) 继续以一流的治疗方式推动研发管道，但成功率主要取决于基础模型系统的质量。在这里，我们采用了一种基于干细胞的方法来发现与目标无关但以通路为中心的小分子细胞因子信号激活剂，以在发育和再生过程中充当形态发生素。公正筛选鉴定出三唑并 [1,5- c]喹唑啉作为骨形态发生蛋白 (BMP) 通路的体外和体内活性放大器。细胞 BMP 输出通过 BMP-Smad 蛋白的增强和持续可用性来刺激，严格依赖于最小的 BMP 输入。整体目标反卷积揭示了一种独特的双重靶向机制，即酪蛋白激酶 1 和磷脂酰肌醇 3-激酶同种型作为有效放大成骨 BMP 信号传导的关键效应物。这项工作强调了 PDD 发现未被识别的多药理学特征的资产，在这种情况下显着扩展了 BMP 调制器的化学和药物空间。

  DOI：

  10.1021/acs.jmedchem.2c01199

文献信息

• Synthesis and Structure−Activity Relationships of Fused Imidazopyridines:  A New Series of Benzodiazepine Receptor Ligands
  作者：Susumu Takada、Takashi Sasatani、Nobuo Chomei、Makoto Adachi、Toshio Fujishita、Masami Eigyo、Shunji Murata、Kazuo Kawasaki、Akira Matsushita

  DOI：10.1021/jm9600609

  日期：1996.1.1

  synthesized and evaluated as benzodiazepine receptor ligands. Affinity to the receptors was greatly affected by the bulkiness of the aryl group at the 2-position, compared to the pyrazoloquinolines such as CGS-9896. Derivatives with an isoxazole moiety at the 2-position showed high binding affinity and in vivo activity. In the imidazo[4,5-c]quinoline series, substitution at the 6-position decreased or abolished

  合成了2-Arylimidazo [4,5-c]喹啉和类似的稠合咪唑并吡啶，并评价为苯并二氮杂receptor受体配体。与吡唑并喹啉如CGS-9896相比，与受体的亲和力受2-位芳基庞大性的影响。在2-位具有异恶唑部分的衍生物显示出高结合亲和力和体内活性。在咪唑并[4,5-c]喹啉系列中，在6-位的取代降低或消除了活性。除7-卤代类似物外，大多数具有未取代异恶唑基的衍生物均表现出拮抗或反向激动剂活性。另一方面，5-甲基异恶唑-3-基或3-甲基异恶唑-5-基衍生物通常表现出激动剂活性。在与非芳族环稠合的咪唑并吡啶中观察到对异恶唑部分的类似取代作用。根据详细的药理评估，S-8510，2-（3-异恶唑基）-3,6,7,9-四氢咪唑并[4,5-d]吡喃++ + [4,3-b]吡啶一磷酸具有弱的反向激动剂选择活性作为治疗老年性痴呆某些症状的治疗候选药物。
• Novel synthetic procedures for C2 substituted imidazoquinolines as ligands for the α/β-interface of the GABAA-receptor
  作者：Markus Draskovits、Daniele Catorci、Laurin Wimmer、Sabah Rehman、David Chan Bodin Siebert、Margot Ernst、Michael Schnürch、Marko D. Mihovilovic

  DOI：10.1007/s00706-022-02988-8

  日期：——

  A series of substituted imidazoquinolines, a structurally related chemotype to pyrazoloquinolinones, a well-known class of GABA_A ligands, was prepared via two synthetic procedures and the efficiency of these procedures were compared. One method relies on classical heterocyclic synthesis, the other one aims at late-stage decoration of a truncated scaffold via direct C–H functionalization. A pharmacological evaluation disclosed that one of the synthesized derivatives showed interesting activity on a α1β3 containing receptor subtype.

  Graphical abstract

  摘要 通过两种合成方法制备了一系列取代的咪唑喹啉类化合物，这些化合物在结构上与吡唑喹啉酮类化合物（一类著名的 GABAA 配体）相关，并对这两种方法的效率进行了比较。一种方法依赖于经典的杂环合成，另一种方法旨在通过直接 C-H 功能化对截短的支架进行后期装饰。药理评估显示，合成的一种衍生物对含有α1β3受体亚型的受体具有有趣的活性。 图表摘要
• NOVEL IMIDAZO [4,5-C]QUINOLINE AND IMIDAZO [4,5-C][1,5]NAPHTHYRIDINE DERIVATIVES AS LRRK2 INHIBITORS
  申请人：Pfizer Inc.

  公开号：EP3350178B1

  公开（公告）日：2021-10-20
• [EN] NOVEL IMIDAZO [4,5-C] QUINOLINE AND IMIDAZO [4,5-C][1,5] NAPHTHYRIDINE DERIVATIVES AS LRRK2 INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS IMIDAZO [4,5-C] QUINOLINE ET IMIDAZO [4,5-C] [1,5] NAPHTHYRIDINE UTILISÉS COMME INHIBITEURS DE LRRK2
  申请人：PFIZER

  公开号：WO2017046675A1

  公开（公告）日：2017-03-23

  The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof wherein R1, R1a, R1b, R2, R4, R5, R6, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
• 7-Phenyl-imidazoquinolin-4(5H)-one derivatives as selective and orally available mPGES-1 inhibitors
  作者：Tomoya Shiro、Keisuke Kakiguchi、Hirotada Takahashi、Hidetaka Nagata、Masanori Tobe

  DOI：10.1016/j.bmc.2013.03.069

  日期：2013.6

  To identify compounds with strong mPGES-1 inhibitory activity and clear in vitro ADME profile, we optimized the lead compound 1 by carrying our substitutions at the C(7)-and C(8)-positions. Replacement of the bromine atom of 1 with various substituents led to identification of the phenyl group as the best C(7)-substituent giving strong inhibitory activity with good in vitro ADME profile. Further SAR examination on both the C(2)-and the C(7)-phenyl groups provided compound 39 as the best candidate for further development. Compound 39 exhibited strong mPGES-1 inhibitory activity (IC50 = 4.1 nM), potent cell-based functional activity (IC50 = 33 nM) with good mPGES-1 selectivity (over 700-fold), excellent in vitro ADME profile, and good oral absorption in rat PK study. (C) 2013 Elsevier Ltd. All rights reserved.