4-(chloromethyl)-2,3-dihydro-1H-indene | 65898-31-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 4-(chloromethyl)-2,3-dihydro-1H-indene
• CAS: 65898-31-9
• 化学式: C₁₀H₁₁Cl
• mdl: MFCD19233899
• 分子量: 166.65
• InChiKey: BZLIAEVSPAPOPT-UHFFFAOYSA-N

物化性质

• 沸点：
  251.3±9.0 °C(Predicted)
• 密度：
  1.139±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  4-(chloromethyl)-2,3-dihydro-1H-indene 在 sodium hydroxide 、 氯化亚砜 作用下， 以 水 、 二甲基亚砜 、 丙酮 、 甲苯 为溶剂， 反应 10.0h， 生成 N-methyl-2-(4-indanyl)acetamide
  参考文献：
  名称：

  Horn Jensen, Eva; Nielsen, Per Halfdan, Heterocycles, 1995, vol. 41, # 11, p. 2441 - 2458

  摘要：

  DOI：
• 作为产物：
  描述：

  茚满 在 吡啶 、 lithium aluminium tetrahydride 、 三氯化铝 、 氯化亚砜 、 sodium hypobromide 、 硫酸 作用下， 以 1,4-二氧六环 、 四氯化碳 、 乙醚 、 二氯甲烷 、 甲苯 、 苯 为溶剂， 反应 146.0h， 生成 4-(chloromethyl)-2,3-dihydro-1H-indene
  参考文献：
  名称：

  Aromatische Spirane, 22. Mitt.: Darstellung von Cyclopenteno-4,5-indan-1-on und 2-Carboxymethyl-bzw. 4-Chlormethyl-indan als Synthone f�r Synthesen von anellierten 2,2?-Spirobiindanonen

  摘要：

  The title compounds were prepared as follows: tert.-butyl-indane (10) was formylated to give a 72:28 mixture of the aldehydes 23a and 23b which were submitted to a Knoevenagel-Doebner condensation to afford the cinnamonic acids 24. From the mixture, the pure stereoisomer 24a was obtained by one crystallization in 57% yield. Its methylester 27a could be quantitatively dealkylated to the methylester 8 by treatment with AlCl3 in toluene. Cyclization to the indanone 9 was then performed via the propionic acid 7 with polyphosphoric acid in 95% yield. From 9 the carboxymethyl derivative 30 was obtained by treatment with dimethylcarbonate and NaH. The second synthone 4-chlormethylindane (19) was prepared from the corresponding alcohol 18 (in 82% yield) which in turn could be obtained from methylester 17 by reduction with LiAlH4. The latter was accessible in 75% yield by dealkylation of ester 13.

  DOI：

  10.1007/bf00813793

文献信息

• [EN] ANTIBACTERIAL COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ANTIBACTÉRIENS ET UTILISATIONS DE CEUX-CI
  申请人：THE GLOBAL ALLIANCE FOR TB DRUG DEV INC

  公开号：WO2017155909A1

  公开（公告）日：2017-09-14

  The present invention relates to compounds of formula (I) including any stereochemically isomeric form thereof, or pharmaceutically acceptable salts thereof, for the treatment of tuberculosis.

  本发明涉及式(I)的化合物，包括其任何立体化异构体或其药学上可接受的盐，用于治疗结核病。
• Antibacterial compounds and uses thereof
  申请人：The Global Alliance for TB Drug Development, Inc.

  公开号：US10508097B2

  公开（公告）日：2019-12-17

  The present invention relates to compounds of formula (I) including any stereochemically isomeric form thereof, or pharmaceutically acceptable salts thereof, for the treatment of tuberculosis.

  本发明涉及用于治疗结核病的式 (I) 化合物，包括其任何立体化学异构体形式，或其药学上可接受的盐类。
• 3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel
  作者：Hamish S. Sutherland、Amy S.T. Tong、Peter J. Choi、Adrian Blaser、Daniel Conole、Scott G. Franzblau、Manisha U. Lotlikar、Christopher B. Cooper、Anna M. Upton、William A. Denny、Brian D. Palmer

  DOI：10.1016/j.bmc.2019.02.026

  日期：2019.4

  Bedaquiline is a new drug of the diarylquinoline class that has proven to be clinically effective against drugresistant tuberculosis, but has a cardiac liability (prolongation of the QT interval) due to its potent inhibition of the cardiac potassium channel protein hERG. Bedaquiline is highly lipophilic and has an extremely long terminal half-life, so has the potential for more-than-desired accumulation in tissues during the relatively long treatment durations required to cure TB. The present work is part of a program that seeks to identify a diarylquinoline that is as potent as bedaquiline against Mycobacterium tuberculosis, with lower lipophilicity, higher clearance, and lower risk for QT prolongation. Previous work led to the identification of compounds with greatly-reduced lipophilicity compounds that retain good anti-tubercular activity in vitro and in mouse models of TB, but has not addressed the hERG blockade. We now present compounds where the C-unit naphthalene is replaced by a 3,5dialkoxy- 4-pyridyl, demonstrate more potent in vitro and in vivo anti-tubercular activity, with greatly attenuated hERG blockade. Two examples of this series are in preclinical development.
• NEUDECK, H.;SCHLOEGL, K., MONATSCH. CHEM., 1981, 112, N 6-7, 801-823
  作者：NEUDECK, H.、SCHLOEGL, K.

  DOI：——

  日期：——
• ANTIBACTERIAL COMPOUNDS AND USES THEREOF
  申请人：The Global Alliance for TB Drug Development, Inc.

  公开号：EP3426255B1

  公开（公告）日：2022-11-30