(3-(甲基氨基)-5-苯基噻吩-2-基)(苯基)甲酮 | 5061-91-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (3-(甲基氨基)-5-苯基噻吩-2-基)(苯基)甲酮
• 英文名称: 9H-indeno[2,1-c]pyridin-9-one
• 英文别名: indeno[2,1-c]pyridin-9-one
• CAS: 5061-91-6
• 化学式: C₁₂H₇NO
• 分子量: 181.194
• InChiKey: SVRDUQFWQVPUHN-UHFFFAOYSA-N

物化性质

• 熔点：
  151-152 °C(Solv: ligroine (8032-32-4))
• 沸点：
  361.0±11.0 °C(Predicted)
• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  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：
  0.0
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  (3-(甲基氨基)-5-苯基噻吩-2-基)(苯基)甲酮 在 盐酸 、 zinc(II) iodide 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-aza-9-hydroxy-9-fluorene carboxylic acid methyl ester
  参考文献：
  名称：

  9-Hydroxyazafluorenes and Their Use in Thrombin Inhibitors

  摘要：

  Optimization of a previously reported thrombin inhibitor, 9-hydroxy-9-fluorenylcarbonyl-l-prolyl-trans-4-aminocyclohexylmethylamide (1), by replacing the aminocyclohexyl P1 group provided a new lead structure, 9-hydroxy-9-fluorenylcarbonyl-l-prolyl-2-aminomethyl-5-chlorobenzylamide (2), with improved potency (K(i) = 0.49 nM for human thrombin, 2x APTT = 0.37 microM in human plasma) and pharmacokinetic properties (F = 39%, iv T(1/2) = 13 h in dogs). An effective strategy for reducing plasma protein binding of 2 and improving efficacy in an in vivo thrombosis model in rats was to replace the lipophilic fluorenyl group in P3 with an azafluorenyl group. Systematic investigation of all possible azafluorenyl P3 isomers and azafluorenyl-N-oxide analogues of 2 led to the identification of an optimal compound, 3-aza-9-hydroxyfluoren-9(R)-ylcarbonyl-l-prolyl-2-aminomethyl-5-chlorobenzylamide (19b), with high potency (K(i) = 0.40 nM, 2x APTT = 0.18 microM), excellent pharmacokinetic properties (F = 55%, T(1/2) = 14 h in dogs), and complete efficacy in the in vivo thrombosis model in rats (inhibition of FeCl(3)-induced vessel occlusions in six of six rats receiving an intravenous infusion of 10 microg/kg/min of 19b). The stereochemistry of the azafluorenyl group in 19b was determined by X-ray crystallographic analysis of its N-oxide derivative (23b) bound in the active site of human thrombin.

  DOI：

  10.1021/jm049423s
• 作为产物：
  描述：

  1-O-ethyl 3-O-methyl pyridin-1-ium-1,3-dicarboxylate;chloride 在 邻四氯苯醌 、 PPA 、 Polyphosphoric acid (PPA) 、 lithium chloride 、 锌 作用下， 反应 4.0h， 生成 (3-(甲基氨基)-5-苯基噻吩-2-基)(苯基)甲酮
  参考文献：
  名称：

  Syntheses of 2-Azafluorenones from 3-Substituted 4-Arylpyridines

  摘要：

  3-Substituted 4-arylpyridines (5a-i) were synthesized in good yields by reaction of mixed copper, zinc aryl organometallics (2a-e) with 1-ethoxycarbonyl-pyridinium chlorides (1a-d) followed by o-chloranil oxidation under reflux in toluene. The 4-arylpyridines (5a-i) are obtained predominantly. Having compounds (5a-i) in hand, a convenient method was developed for the synthesis of 2-azafluorenones (7a-f) by using cyclization of 4-arylpyridines (5a-i) with polyphosphoric acid.

  DOI：

  10.3987/com-92-6199

文献信息

• Thrombin inhibitors
  申请人：——

  公开号：US20020119992A1

  公开（公告）日：2002-08-29

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1 or a pharmaceutically acceptable salt thereof, e.g. where R 3 is —CH 2 NH 2 , —CH 2 CH 2 NH 2 , or —CH 2 NHC(O)OC(CH 3 ) 3 .

  该发明的化合物在抑制凝血酶和相关血栓闭塞方面具有以下结构： 1 或其药用可接受的盐，例如其中R 3 为—CH 2 NH 2 ，—CH 2 CH 2 NH 2 ，或—CH 2 NHC(O)OC(CH 3 ) 3 。
• Synthesis and metallation of 2-(pyridyl)benzoic acids and ethyl 2-(pyridyl)benzoates: a new route to azafluorenones
  作者：Anne-Sophie Rebstock、Florence Mongin、François Trécourt、Guy Quéguiner

  DOI：10.1016/s0040-4020(03)00761-0

  日期：2003.6

  The ring deprotonation of 2-(2- and 4-pyridyl)benzoic acids using lithium dialkylamides in THF at rt, and the in situ cyclization afforded 4- and 2-azafluorenones, respectively. 1-Azafluorenone was obtained from ethyl 2-(3-pyridyl)benzoate using a similar protocol.

  使用二烷基氨基锂在rt在THF中对2-（2-和4-吡啶基）苯甲酸进行环去质子化，并进行原位环化，分别得到4-和2-氮杂芴酮。使用类似的方案，从2-（3-吡啶基）苯甲酸乙酯获得1-氮杂芴酮。
• Intramolecular Acylation of Unactivated Pyridines or Arenes via Multiple C–H Functionalizations: Synthesis of All Four Azafluorenones and Fluorenones
  作者：Joydev K. Laha、Krupal P. Jethava、Sagarkumar Patel、Ketul V. Patel

  DOI：10.1021/acs.joc.6b02065

  日期：2017.1.6

  unactivated pyridines via multiple C(sp3/sp2)–H functionalizations of a methyl, hydroxymethyl, or aldehyde group has been developed providing a general access to all four azafluorenones. The application of this protocol is further demonstrated to the synthesis of azafluorenone related fused nitrogen heterocycles and fluorenones. In addition, design and synthesis of a novel fluorene based organic emitter for

  通过甲基，羟甲基或醛基团的多个C（sp 3 / sp 2）–H官能化作用，未活化的吡啶进行了前所未有的分子内酰化反应，从而提供了对所有四个氮杂氟烯酮的通用途径。该方案的应用进一步证明了与氮杂芴酮相关的稠合氮杂环和芴酮的合成。另外，还报道了潜在用于有机发光器件（OLED）的新型芴基有机发射体的设计和合成。
• Spiro-tricyclicaromatic succinimide derivatives
  申请人：Alcon Laboratories, Inc.

  公开号：US05070100A1

  公开（公告）日：1991-12-03

  Disclosed are substituted or unsubstituted planar tricyclic fluorene or nuclear analogs thereof, spiro-coupled to a five-membered ring containing a secondary amide, and the pharmaceutically acceptable salts thereof. These compounds are useful, inter alia in the treatment of diabetes. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when indicated for, inter alia, long term, prophylactic treatment of the diabetes syndrome. A particularly preferred class of compounds comprise difluoro-dialkoxy substituted spiro-(9H-fluorene-9,4'-imidazolidine)-2,40 ,5-diones.

  揭示了取代或未取代的平面三环芴或其核类似物，与含有次级酰胺的五元环螺合，以及其药用可接受的盐。这些化合物在糖尿病治疗中有用。还公开了制备这种化合物的方法；包含这种化合物的药物组合物；以及治疗方法，包括在适用于长期、预防性治疗糖尿病综合症时，给予这种化合物和组合物。一种特别优选的化合物类别包括二氟二烷氧基取代的螺-(9H-芴-9,4'-咪唑啉)-2,4',5-二酮。
• Nitrogen introduction of spirobifluorene to form α-, β-, γ-, and δ-aza-9,9′-spirobifluorenes: New bipolar system for efficient blue organic light-emitting diodes
  作者：Peng Wu、Jun Zhu、Zhen Zhang、Dehai Dou、Hedan Wang、Bin Wei、Zixing Wang

  DOI：10.1016/j.dyepig.2018.03.066

  日期：2018.9

  γ-aza-SBF and δ-aza-SBF showed overlapped HOMO and LUMO orbitals. The aza-SBFs showed excellent bipolar features and good thermal stabilities than those of SBFs. The maximum current efficiencies (CE) of α-, β-, γ-, and δ-aza-SBF-based OLEDs were 28.8, 24.9, 25.5, and 27.2 cd/A, respectively. Compared to the SBF, all of four aza-SBFs showed better devices performances. The CE and power efficiency (PE) of OLED

  合成了四个在一个芴部分的不同位置带有氮原子的aza-9,9'-spirbibifluorenes（aza-SBFs），以研究其结构性质之间的关系。α-Aza-SBF和β-aza-SBF几乎完全分开了最高占据分子轨道（HOMO）和最低未占据分子轨道（LUMO），而γ-aza-SBF和δ-aza-SBF显示出HOMO和LUMO重叠轨道。氮杂-SBF比SBF表现出优异的双极性特性和良好的热稳定性。α-，β-，γ-和δ-aza-SBF的最大电流效率（CE）的OLED分别为28.8、24.9、25.5和27.2 cd / A。与SBF相比，所有四个aza-SBF均显示出更好的器件性能。基于α-氮杂-SBF的OLED的CE和功率效率（PE）为28.8 cd / A和22.6 lm / W，而基于SBF的OLED仅为12.3 cd / A和8.2 lm / W。基于氮-氮杂-SBF的OLED的最大外部量子效率为15