2,3-二氢-1H-环戊并[B]喹啉-9-胺 | 18528-78-4

• 物质功能分类: 医药中间体 - 杂环化合物 - 喹啉类化合物
• 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
• 中文名称: 2,3-二氢-1H-环戊并[B]喹啉-9-胺
• 中文别名: 2,3-二氢-1H-环戊并[b]喹啉-9-胺
• 英文名称: 2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamine
• 英文别名: 2,3-dihydro-1H-cyclopenta[b]quinolin-9-amine；2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamine；2,3-Dihydro-1H-cyclopenta[b]chinolin-9-ylamin
• CAS: 18528-78-4
• 化学式: C₁₂H₁₂N₂
• mdl: MFCD00618440
• 分子量: 184.241
• InChiKey: GYSCQDBTSDBCGY-UHFFFAOYSA-N

物化性质

• 熔点：
  175-176 °C
• 沸点：
  394.5±42.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P301+P312,P302+P352,P304+P340,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2,3-二氢-1H-环戊并[B]喹啉-9-胺 在 硫酸 、 水 、 sodium nitrite 作用下， 生成 2,3-Dihydro-1H-cyclopentachinolin-9-ol
  参考文献：
  名称：

  Lamant, Annales de Chimie (Cachan, France), 1959, vol. <13> 4, p. 87,108

  摘要：

  DOI：
• 作为产物：
  描述：

  2-anilino-cyclopent-1-enecarbonitrile 在 三氯化铝 作用下， 生成 2,3-二氢-1H-环戊并[B]喹啉-9-胺
  参考文献：
  名称：

  Lamant, Annales de Chimie (Cachan, France), 1959, vol. <13> 4, p. 87,108

  摘要：

  DOI：

文献信息

• Cationic amphiphilic bolaamphiphile-based delivery of antisense oligonucleotides provides a potentially microbiome sparing treatment for C. difficile
  作者：Arun K. Sharma、Jacek Krzeminski、Volkmar Weissig、John P. Hegarty、David B. Stewart

  DOI：10.1038/s41429-018-0056-9

  日期：2018.8

  Conventional antibiotics for C. difficile infection (CDI) have mechanisms of action without organismal specificity, potentially perpetuating the dysbiosis contributing to CDI, making antisense approaches an attractive alternative. Here, three (APDE-8, CODE-9, and CYDE-21) novel cationic amphiphilic bolaamphiphiles (CABs) were synthesized and tested for their ability to form nano-sized vesicles or vesicle-like aggregates (CABVs), which were characterized based on their physiochemical properties, their antibacterial activities, and their toxicity toward colonocyte (Caco-2) cell cultures. The antibacterial activity of empty CABVs was tested against cultures of E. coli, B. fragilis, and E. faecalis, and against C. difficile by “loading” CABVs with 25-mer antisense oligonucleotides (ASO) targeting dnaE. Our results demonstrate that empty CABVs have minimal colonocyte toxicity until concentrations of 71 µM, with CODE-9 demonstrating the least toxicity. Empty CABVs had little effect on C. difficile growth in culture (MIC90 ≥ 160 µM). While APDE-8 and CODE-9 nanocomplexes demonstrated high MIC90 against C. difficile cultures (>300 µM), CYDE-21 nanocomplexes demonstrated MIC90 at CABV concentrations of 19 µM. Empty CABVs formed from APDE-8 and CODE-9 had virtually no effect on E. coli, B. fragilis, and E. faecalis across all tested concentrations, while empty CYDE-21 demonstrated MIC90 of >160 µM against E. coli and >40 µM against B. fragilisand E. faecalis. Empty CABVs have limited antibacterial activity and they can deliver an amount of ASO effective against C. difficile at CABV concentrations associated with limited colonocyte toxicity, while sparing other bacteria. With further refinement, antisense therapies for CDI may become a viable alternative to conventional antibiotic treatment.

  常规抗生素用于艰难梭菌感染(CDI)的作用机制缺乏对特定生物的选择性，可能加剧导致CDI的菌群失调，因此使得反义方法成为一种有吸引力的替代方案。本文合成了三种新型阳离子两亲性双头脂质(CABs)，即APDE-8、CODE-9和CYDE-21，并测试了它们形成纳米尺寸囊泡或囊泡样聚集体(CABVs)的能力。这些CABVs的物理化学性质、抗菌活性以及对结肠上皮细胞(Caco-2)细胞的毒性进行了表征。研究人员测试了空CABVs对大肠杆菌、脆弱拟杆菌和粪肠球菌以及艰难梭菌的抗菌活性，具体方法是将CABVs装载25聚反义寡核苷酸(ASO)，目标是dnaE。结果显示，空CABVs的结肠上皮细胞毒性极低，直至浓度达到71微摩尔，其中CODE-9的毒性最小。空CABVs对艰难梭菌在培养中的生长影响甚微(MIC90≥160微摩尔)。APDE-8和CODE-9纳米复合物对艰难梭菌培养表现出高MIC90(>300微摩尔)，而CYDE-21纳米复合物的MIC90在CABV浓度为19微摩尔时出现。APDE-8和CODE-9形成的空CABVs对所有测试浓度下的大肠杆菌、脆弱拟杆菌和粪肠球菌几乎没有影响，而空CYDE-21对大肠杆菌的MIC90为>160微摩尔，对脆弱拟杆菌和粪肠球菌的MIC90为>40微摩尔。空CABVs的抗菌活性有限，但它们能在有限的结肠上皮细胞毒性相关浓度下有效传递ASO以对抗艰难梭菌，同时不影响其他细菌。进一步完善后，针对CDI的反义疗法可能成为传统抗生素治疗的切实替代方案。
• Sulfuric acid-modified PEG-6000 (PEG-OSO3H): an efficient, bio-degradable and reusable polymeric catalyst for the solvent-free synthesis of poly-substituted quinolines under microwave irradiation
  作者：Alireza Hasaninejad、Abdolkarim Zare、Mohsen Shekouhy、Javad Ameri-Rad

  DOI：10.1039/c0gc00953a

  日期：——

  acid-modified polyethylene glycol 6000 (PEG-OSO3H) is applied as an efficient and eco-friendly polymeric catalyst for Friedländer synthesis of poly-substituted quinolines from 2-aminoaryl ketones (or anthranilonitrile) and carbonyl compounds possessing a reactive methylene group under microwave irradiation and solvent-free conditions. The reactions are completed in short times, and the products are obtained

  硫酸改性聚乙二醇6000（PEG-OSO 3 H）被用作一种高效且环保的聚合物催化剂 Friedländer合成多取代基 喹啉 由2-氨基芳基 酮类 （或者 蒽腈） 和 羰基化合物 在微波辐射下具有反应性亚甲基 溶剂无条件。反应在短时间内完成，并且以良好至优异的产率获得产物。
• Novel Tacrine Analogues for Potential Use against Alzheimer's Disease:  Potent and Selective Acetylcholinesterase Inhibitors and 5-HT Uptake Inhibitors
  作者：Maureen T. MKenna、George R. Proctor、Louise C. Young、Alan L. Harvey

  DOI：10.1021/jm970150t

  日期：1997.10.1

  synthesized and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase, and neuronal uptake of 5-HT (serotonin) and noradrenaline. Changes in the size of the carbocyclic ring of tacrine produced modest potency against cholinesterase enzymes. Addition of a fourth ring resulted in compounds with marked selectivity for acetylcholinesterase (AChE) over butyrylcholinesterase (BChE):

  已经合成了几种新的他克林类似物，并测试了它们抑制乙酰胆碱酯酶，丁酰胆碱酯酶以及5-HT（5-羟色胺）和去甲肾上腺素的神经元摄取的能力。他克林碳环大小的变化产生了适度的针对胆碱酯酶的效力。第四个环的加成导致化合物对乙酰胆碱酯酶（AChE）的选择性比对丁酰胆碱酯酶（BChE）的选择性高：例如6-氨基-4,5-苯并-5H-环戊[1,2-b]-喹啉（14a）具有针对AChE的IC50为0.35 microM，针对BChE的IC50为3.1 microM。一些四环化合物作为神经元摄取5-羟色胺的抑制剂的活性比他克林高100-400倍，特别是13-氨基-6,7-二氢-5H-苯并-[3,4]环庚[1,2-b]喹啉（18），其IC50为20 nM。这些化合物有望促进胆碱能和单胺能传递。他们应该对记忆障碍模型进行研究。
• [EN] HISTONE METHYLTRANSFERASE INHIBITORS<br/>[FR] INHIBITEURS D'HISTONE MÉTHYLTRANSFÉRASE
  申请人：GLOBAL BLOOD THERAPEUTICS INC

  公开号：WO2017142947A1

  公开（公告）日：2017-08-24

  The present disclosure provides certain compounds of formula (I) 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 hemoglobinpathies such as beta-thalassemia and sickle cell disease. Also provided are pharmaceutical compositions containing such compounds as well as processes and intermediates for preparing such compounds.

  本公开提供了某些公式(I)的化合物，这些化合物是组蛋白甲基转移酶G9a和/或GLP的抑制剂，因此可用于治疗可通过抑制G9a和/或GLP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以及制备这些化合物的过程和中间体。
• The Divergent Transformations of Aromatic<i>o</i>-Aminonitrile with Carbonyl Compound
  作者：Jianhong Tang、Jiarong Li、Lijun Zhang、Shuling Ma、Daxin Shi、Qi Zhang、Liupan Yang、Xiuzhen Wang、Xuan Liu、Change Liu

  DOI：10.1002/jhet.804

  日期：2012.5

  A modified Friedländer conversion of the cyclocondensation of aromatic o‐aminonitriles with carbonyl compounds was discovered. Systematic studies reveal that both the new transformation and the classic Friedländer annulation in the presence of ZnCl2 constitute a pair of divergent reaction, and thecontrolled PDF transformation of this divergent reaction was achieved in the present of bases.

  发现了芳族邻氨基腈与羰基化合物的环缩合反应的改进的Friedländer转化。系统研究表明，在存在ZnCl 2的情况下，新的转化和经典的Friedländer圆环构成了一对发散反应，并且在碱的存在下实现了该发散反应的受控PDF转化。