(4-溴-2-氯苯氧基)乙酸 | 77228-67-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (4-溴-2-氯苯氧基)乙酸
• 英文名称: 2-(4-bromo-2-chlorophenoxy)acetic acid
• 英文别名: (4-Bromo-2-chlorophenoxy)acetic acid
• CAS: 77228-67-2
• 化学式: C₈H₆BrClO₃
• mdl: MFCD03422201
• 分子量: 265.491
• InChiKey: VCDBRFZHSIYFRO-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  (4-溴-2-氯苯氧基)乙酸 生成 乙酰氯
  参考文献：
  名称：

  CDC42 INHIBITOR AND USES THEREOF

  摘要：

  公开号：

  EP2716292B1
• 作为产物：
  描述：

  邻氯苯氧乙酸 在 三氯化铝 、 溴 作用下， 生成 (4-溴-2-氯苯氧基)乙酸
  参考文献：
  名称：

  新化合物作为植物生长调节剂。

  摘要：

  DOI：

  10.1021/ja01195a604

文献信息

• Design and synthesis of α-phenoxy-N-sulfonylphenyl acetamides as Trypanosoma brucei Leucyl-tRNA synthetase inhibitors
  作者：Weixiang Xin、Zezhong Li、Qing Wang、Jin Du、Mingyan Zhu、Huchen Zhou

  DOI：10.1016/j.ejmech.2019.111827

  日期：2020.1

  HAT is urgently needed. Leucyl-tRNA synthetase (LeuRS), a recently clinically validated antimicrobial target, is an attractive target for development of antitrypanosomal drugs. In this work, we report a series of α-phenoxy-N-sulfonylphenyl acetamides as T. brucei LeuRS inhibitors. The most potent compound 28g showed an IC50 of 0.70 μM which was 250-fold more potent than the starting hit compound 1. The

  由寄生性原生动物锥虫锥虫引起的人类非洲锥虫病（HAT）是热带地区的致命疾病之一，目前的药物不足。因此，迫切需要开发用于HAT的新药。亮氨酰-tRNA合成酶（LeuRS）是最近经过临床验证的抗微生物靶标，是开发抗锥虫病药物的有吸引力的靶标。在这项工作中，我们报告了一系列作为T. brucei LeuRS抑制剂的α-苯氧基-N-磺酰基苯基乙酰胺。最有效的化合物28g的IC50为0.70μM，比起始命中化合物1的IC50强250倍。还讨论了结构-活性关系。这些乙酰胺为进一步开发临床上有用的抗胰锥虫剂提供了新的支架和先导化合物。
• Discovery of N-(4-sulfamoylphenyl)thioureas as Trypanosoma brucei leucyl-tRNA synthetase inhibitors
  作者：Fenglong Zhang、Jin Du、Qing Wang、Qinghua Hu、Jiong Zhang、Dazhong Ding、Yaxue Zhao、Fei Yang、Enduo Wang、Huchen Zhou

  DOI：10.1039/c3ob40236c

  日期：——

  Human African trypanosomiasis (HAT) is one of the most neglected diseases in the tropic regions, which is fatal if not treated in time. There is an urgent need for new therapeutics, especially those in new chemical classes. Leucyl-tRNA synthetase (LeuRS) has been paid much attention as a recently clinically validated antimicrobial target. Our group has previously reported T. brucei LeuRS (TbLeuRS) inhibitors, including benzoxaboroles targeting the editing site and pyrrolinones targeting the synthetic site. Here we report the discovery of N-(4-sulfamoylphenyl)thioureas as a new class of TbLeuRS inhibitors. The R1 and R2 groups, reminiscent of the leucyl and adenyl regions of aa-AMP and aa-AMS, were optimized to result in a significant 13-fold increase of inhibitory activity (compound 19, IC50 = 13.7 μM). Aided by ligand–protein docking, the 1,3-substitution at the central phenyl ring was predicted and proved to give significantly improved activity (59, IC50 = 1.1 μM). This work provided a new scaffold for the exploration of novel inhibitors against TbLeuRS, which may become potential therapeutics for the treatment of HAT.

  非洲锥虫病(Human African trypanosomiasis, HAT)是热带地区最为忽视的致死性疾病之一,若不及时治疗,将会有致命风险。迫切需要新的治疗药物,特别是新的化学类别中的药物。白氨酰-tRNA合成酶(Leucyl-tRNA synthetase, LeuRS)作为一个最近的临床验证的抗菌靶点,受到了广泛关注。我们的研究团队前期报道了针对编辑位点的苯并氧杂硼啶类和针对合成位点的吡咯烷酮类刚果锥虫LeuRS(TbLeuRS)抑制剂。在此,我们报道了N-(4-磺酰胺基苯基)硫脲作为新型TbLeuRS抑制剂的发现。借鉴于aa-AMP和aa-AMS中的氨酰基和腺苷基结构的R1和R2基团,经过优化设计,显著提高了13倍的抑制活性(化合物19, IC50 = 13.7 μM)。通过配体-蛋白对接辅助,预测并验证了在苯环上的1,3-取代,能显著提高活性(化合物59, IC50 = 1.1 μM)。这项工作为探索新型TbLeuRS抑制剂提供了一个新的骨架,这些抑制剂可能成为治疗HAT的潜在药物。
• AMINO ALCOHOL DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, AND USE OF THESE
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1679304A1

  公开（公告）日：2006-07-12

  The present invention provides compounds represented by general formula (I): a prodrug thereof, or pharmaceutical acceptable salts thereof, wherein R1 is hydrogen or lower alkyl; each of R2 and R3 is independently hydrogen or lower alkyl; each of R4, R5 and R6 is independently hydrogen, halogen, lower alkyl or lower alkoxy; R7 is hydrogen or lower alkyl; R8 is hydrogen, halogen, lower alkyl, lower alkoxy, etc; R9 is -COR10, -A1-COR10, -O-A2-COR10, etc; Ar is optionally substituted phenyl or heteroaryl; and A is a bond, -OCH2-, etc, which exhibit potent and selective β3-adrenoceptor stimulating activities. The present invention also provides pharmaceutical compositions containing said compound, and uses thereof.

  本发明提供了由通式（I）表示的化合物： 其前药，或其药用可接受的盐，其中R1是氢或较低的烷基；R2和R3中的每一个独立地是氢或较低的烷基；R4、R5和R6中的每一个独立地是氢、卤素、较低的烷基或较低的烷氧基；R7是氢或较低的烷基；R8是氢、卤素、较低的烷基、较低的烷氧基等；R9是-COR10、-A1-COR10、-O-A2-COR10等；Ar是可选择地取代的苯基或杂环芳基；A是键，-OCH2-等，具有强效和选择性的β3-肾上腺素受体刺激活性。本发明还提供了含有所述化合物的药物组合物，以及其用途。
• Cdc42 Inhibitor and Uses Thereof
  申请人：Lu Qun

  公开号：US20140194451A1

  公开（公告）日：2014-07-10

  Compounds which inhibit the small G protein Rho GTPase cell division cycle protein Cdc42 are provided. Morphological analyses of filopodia, western blots of Ccd42 phosphorylation, and effects on cellular wound healing and on growth cone formation all demonstrate that the described compounds are able to inhibit all tested Cdc42-mediated processes. The compounds effectively inhibit, the effects of Cdc42 and effectively inhibit Cdc42-related cellular functions involving actin, such as Golgi organization and cell movement. Furthermore, the described Cdc42 inhibitor compounds may be provided as a medicament for the treatment of various conditions.

  提供了抑制小G蛋白Rho GTP酶细胞分裂周期蛋白Cdc42的化合物。对丝状伪足的形态分析、Ccd42磷酸化的西方印迹、对细胞愈合和生长锥形成的影响均表明，所述化合物能够抑制所有经过测试的Cdc42介导的过程。这些化合物有效地抑制了Cdc42的作用，并有效地抑制了涉及肌动蛋白的Cdc42相关细胞功能，如高尔基体组织和细胞运动。此外，所述的Cdc42抑制剂化合物可以作为治疗各种疾病的药物提供。
• Discovery, synthesis and biological characterization of a series of <i>N</i>-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1<i>H</i>-pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators
  作者：Swagat Sharma、Lauren Lesiak、Christopher D. Aretz、Yu Du、Sushil Kumar、Nagsen Gautam、Yazen Alnouti、Nikilesh V. Dhuria、Yashpal S. Chhonker、C. David Weaver、Corey R. Hopkins

  DOI：10.1039/d1md00129a

  日期：——

  The present study describes the discovery and characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as G protein-gated inwardly-rectifying potassium (GIRK) channel activators. From our previous lead optimization efforts, we have identified a new ether-based scaffold and paired this with a novel sulfone-based head group to identify a potent

  本研究描述了一系列N -(1-(1,1-二氧化四氢噻吩-3-基)-3-甲基-1 H-吡唑-5-基)乙酰胺醚作为 G 蛋白内门控的发现和表征-整流钾（GIRK）通道激活剂。从我们之前的先导化合物优化工作中，我们已经确定了一种新的基于醚的支架，并将其与一种新型的基于砜的头基配对，以确定一种有效且选择性的 GIRK1/2 激活剂。此外，我们在第 1 层 DMPK 测定中评估了这些化合物，并确定了作为 GIRK1/2 激活剂显示纳摩尔效力的化合物，与典型的基于尿素的化合物相比，其代谢稳定性得到了改善。