2-[2-bromo-4-(trifluoromethoxy)phenyl]-1,3-dioxolane | 1321963-18-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[2-bromo-4-(trifluoromethoxy)phenyl]-1,3-dioxolane
• CAS: 1321963-18-1
• 化学式: C₁₀H₈BrF₃O₃
• 分子量: 313.071
• InChiKey: QWVYPTGLTQVOAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[2-bromo-4-(trifluoromethoxy)phenyl]-1,3-dioxolane 在 盐酸 、 caesium carbonate 、 溶剂黄146 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.83h， 生成 (S)-N-(2-(4-methylpiperazin-1-yl)-4-(trifluoromethoxy)-benzyl)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-amine
  参考文献：
  名称：

  Structure–Activity Relationships of Antitubercular Nitroimidazoles. 3. Exploration of the Linker and Lipophilic Tail of ((S)-2-Nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine (6-Amino PA-824).

  摘要：

  The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and in animal models and is currently in clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, and these were tested for whole-cell activity against both replicating and nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates of the deazaflavin-dependent nitroreductase (Ddn) from Mtb that reductively activates these pro-drugs. These studies yielded multiple compounds with 40 nM aerobic whole cell activity and 1.6 mu M anaerobic whole cell activity: 10-fold improvements over both characteristics from the parent molecule. Some of these compounds exhibited enhanced solubility with acceptable stability to microsomal and in vivo metabolism. Analysis of the conformational preferences of these analogues using quantum chemistry suggests a preference for a pseudoequatorial orientation of the linker and lipophilic tail.

  DOI：

  10.1021/jm1010644
• 作为产物：
  描述：

  (E)-2-bromo-1-styryl-4-(trifluoromethoxy)benzene 在 sodium periodate 、 四氧化锇 、 对甲苯磺酸 作用下， 以 水 、 丙酮 、 叔丁醇 、 苯 为溶剂， 反应 24.0h， 生成 2-[2-bromo-4-(trifluoromethoxy)phenyl]-1,3-dioxolane
  参考文献：
  名称：

  Structure–Activity Relationships of Antitubercular Nitroimidazoles. 3. Exploration of the Linker and Lipophilic Tail of ((S)-2-Nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine (6-Amino PA-824).

  摘要：

  The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and in animal models and is currently in clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, and these were tested for whole-cell activity against both replicating and nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates of the deazaflavin-dependent nitroreductase (Ddn) from Mtb that reductively activates these pro-drugs. These studies yielded multiple compounds with 40 nM aerobic whole cell activity and 1.6 mu M anaerobic whole cell activity: 10-fold improvements over both characteristics from the parent molecule. Some of these compounds exhibited enhanced solubility with acceptable stability to microsomal and in vivo metabolism. Analysis of the conformational preferences of these analogues using quantum chemistry suggests a preference for a pseudoequatorial orientation of the linker and lipophilic tail.

  DOI：

  10.1021/jm1010644

文献信息

• TW2016/5858
  申请人：——

  公开号：——

  公开（公告）日：——
• FUSED PYRAZOLE DERIVATIVE
  申请人：SUMITOMO DAINIPPON PHARMA CO., LTD.

  公开号：US20160318933A1

  公开（公告）日：2016-11-03

  The present invention provides a cyclic aminomethyl pyrimidine derivative including a pharmaceutically acceptable salt thereof with high selectivity for dopamine D 4 receptor, which is useful for treating a disease such as attention deficit hyperactivity disorder. Specifically, the present invention relates no a compound of formula (1) or a pharmaceutically acceptable salt thereof, wherein n and m are independently 1 or 2; W 1 , W 3 , and W 4 are independently single bond or optionally-substituted C 1-4 alkylene group; W 2 is optionally-substituted C 1-4 alkylene group; R 1 and R 2 are independently hydrogen atom, etc.; R 3 is hydrogen atom, halogen atom, etc.; X 1 and X 2 are independently single bond, oxygen atom, etc.; ring Q 1 is optionally-substituted 5- to 10-membered heteroaryl group, etc.; ring Q 2 is optionally-substituted 6-membered heteroaryl group, etc.
• [EN] FUSED PYRAZOLE DERIVATIVE<br/>[FR] DÉRIVÉ DE PYRAZOLE FUSIONNÉ<br/>[JA] 縮合ピラゾール誘導体
  申请人：SUMITOMO DAINIPPON PHARMA CO LTD

  公开号：WO2015060348A1

  公开（公告）日：2015-04-30

  　本発明は、ドパミンＤ４受容体に対して選択性の高い作用を示し、注意欠陥多動性障害等の治療剤として有用な環状アミノメチルピリミジン誘導体及びその薬学上許容される塩を提供する。具体的に本発明は、式（１）で表される化合物またはその薬学上許容される塩に関する。 ［式中、ｎおよびｍは、それぞれ独立して、１または２を表し；Ｗ１、Ｗ３およびＷ４は、それぞれ独立して、単結合、または置換されていてもよいＣ１－４アルキレン基を表し；Ｗ２は、置換されていてもよいＣ１－４アルキレン基を表し；ＲｌおよびＲ２は、それぞれ独立して、水素原子等を表し；Ｒ３は、水素原子、ハロゲン原子等を表し；Ｘ１およびＸ２は、それぞれ独立して、単結合、酸素原子等を表し；環Ｑｌは置換されていてもよい５員～１０員のヘテロアリール基等を表し；環Ｑ２は、置換されていてもよい６員のヘテロアリール基等を表す。］
• Structure–Activity Relationships of Antitubercular Nitroimidazoles. 3. Exploration of the Linker and Lipophilic Tail of ((<i>S</i>)-2-Nitro-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine (6-Amino PA-824).
  作者：Joseph Cherian、Inhee Choi、Amit Nayyar、Ujjini H. Manjunatha、Tathagata Mukherjee、Yong Sok Lee、Helena I. Boshoff、Ramandeep Singh、Young Hwan Ha、Michael Goodwin、Suresh B. Lakshminarayana、Pornwaratt Niyomrattanakit、Jan Jiricek、Sindhu Ravindran、Thomas Dick、Thomas H. Keller、Veronique Dartois、Clifton E. Barry

  DOI：10.1021/jm1010644

  日期：2011.8.25

  The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and in animal models and is currently in clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, and these were tested for whole-cell activity against both replicating and nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates of the deazaflavin-dependent nitroreductase (Ddn) from Mtb that reductively activates these pro-drugs. These studies yielded multiple compounds with 40 nM aerobic whole cell activity and 1.6 mu M anaerobic whole cell activity: 10-fold improvements over both characteristics from the parent molecule. Some of these compounds exhibited enhanced solubility with acceptable stability to microsomal and in vivo metabolism. Analysis of the conformational preferences of these analogues using quantum chemistry suggests a preference for a pseudoequatorial orientation of the linker and lipophilic tail.