2-(4-(benzyloxy)-2-bromophenyl)-1,3-dioxolane | 1226773-35-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(4-(benzyloxy)-2-bromophenyl)-1,3-dioxolane
• CAS: 1226773-35-8
• 化学式: C₁₆H₁₅BrO₃
• 分子量: 335.197
• InChiKey: WSZVIIFMDNGPAD-UHFFFAOYSA-N

物化性质

• 沸点：
  420.2±45.0 °C(Predicted)
• 密度：
  1.421±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  27.69
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(4-(benzyloxy)-2-bromophenyl)-1,3-dioxolane 在 sodium tetrahydroborate 、 正丁基锂 、 硼酸三异丙酯 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.0h， 生成 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)-3-methylbutan-2-one
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship of Trypanosoma brucei Leucyl-tRNA Synthetase Inhibitors as Antitrypanosomal Agents

  摘要：

  African trypanosomiasis, caused by the protozoal pathogen Tlypanosoma brucei (T. brucei), is one of the most neglected tropical diseases that are in great need of new drugs. We report the design and synthesis of T. bruceileucyl-tRNA synthetase (TbLeuRS) inhibitors and their structure activity relationship. Benzoxaborole was used as the core structure and C(6) was modified to achieve improved affinity bared on docking results that showed further binding space at this position. Indeed, compounds with C(7) substitutions showed diminished activity due to clash with the eukaryote specific I4ae helix while substitutions at C(6) gave enhanced affinity. TbLeuRS inhibitors with IC50 as low as 1.6 mu M were discovered, and the structure activity relationship was discussed. The most potent enzyme inhibitors also showed excellent T.brucei parasite growth inhibition activity. This is the first time that TbLeuRS inhibitors are reported, and this study suggests that leucyl-tRNA synthetase (LeuRS) could be a potential target for antiparasitic drug development.

  DOI：

  10.1021/jm101225g
• 作为产物：
  描述：

  2-溴-4-氟苯甲醛 在 potassium tert-butylate 、 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 13.0h， 生成 2-(4-(benzyloxy)-2-bromophenyl)-1,3-dioxolane
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Studies of O-Biphenyl-3-yl Carbamates as Peripherally Restricted Fatty Acid Amide Hydrolase Inhibitors

  摘要：

  The peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAP.) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3'-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date.

  DOI：

  10.1021/jm4007017

文献信息

• Discovery of Novel Benzoxaborole-Based Potent Antitrypanosomal Agents
  作者：Dazhong Ding、Yaxue Zhao、Qingqing Meng、Dongsheng Xie、Bakela Nare、Daitao Chen、Cyrus J. Bacchi、Nigel Yarlett、Yong-Kang Zhang、Vincent Hernandez、Yi Xia、Yvonne Freund、Maha Abdulla、Kean-Hooi Ang、Joseline Ratnam、James H. McKerrow、Robert T. Jacobs、Huchen Zhou、Jacob J. Plattner

  DOI：10.1021/ml100013s

  日期：2010.7.8

  We report the discovery of benzoxaborole antitrypanosomal agents and their structure activity relationships on central linkage groups and different substitution patterns in the sulfur-linked series. The compounds showed in vitro growth inhibition IC(50) values as low as 0.02 mu g/mL and in vivo efficacy in acute murine infection models against nryapnosoma brucei.