3-(2,6-dichlorobenzyloxy)benzoyl chloride | 221242-56-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(2,6-dichlorobenzyloxy)benzoyl chloride
• 英文别名: 3-[(2,6-Dichlorobenzyl)oxy]benzoyl chloride；3-[(2,6-dichlorophenyl)methoxy]benzoyl chloride
• CAS: 221242-56-4
• 化学式: C₁₄H₉Cl₃O₂
• mdl: MFCD12197989
• 分子量: 315.583
• InChiKey: QLWUMUXWAUDNJU-UHFFFAOYSA-N

物化性质

• 沸点：
  421.8±35.0 °C(Predicted)
• 密度：
  1.406±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  3-(2,6-dichlorobenzyloxy)benzoyl chloride 在 sodium hydride 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 2.5h， 生成 5-Amino-1-tert-butyl-3-[3-(2,6-dichloro-benzyloxy)-phenyl]-1H-pyrazole-4-carbonitrile
  参考文献：
  名称：

  Generation of Monospecific Nanomolar Tyrosine Kinase Inhibitors via a Chemical Genetic Approach

  摘要：

  Selective protein kinase inhibitors are highly sought after as tools for studying cellular signal transduction cascades, yet few have been discovered due to the highly conserved fold of kinase catalytic domains. Through a combination of small molecule synthesis and protein mutagenesis, a highly potent (IC50 = 1.5 nM) and uniquely specific inhibitor (4-amino-1-tert-butyl-3-(1'-naphthyl)pyrazolo[3,4-d]pyrimidine) of a rationally engineered v-Src tyrosine kinase (Ile338Gly v-Src) has been identified. Both the potency and specificity of this compound surpass those of any known Src family tyrosine kinase inhibitors. The molecule strongly inhibits the engineered v-Src in whole cells but does not inhibit tyrosine phosphorylation in cells that express only wild-type tyrosine kinases. In addition, the inhibitor selectively disrupts transformation in cells that express the target v-Src. The structural degeneracy of kinase active sites should allow the same complementary inhibitor/protein design strategy to be widely applicable across this entire enzyme superfamily.

  DOI：

  10.1021/ja983267v
• 作为产物：
  描述：

  3-((2,6-dichlorobenzyl)oxy)benzoic acid 在 氯化亚砜 作用下， 反应 24.0h， 生成 3-(2,6-dichlorobenzyloxy)benzoyl chloride
  参考文献：
  名称：

  用于治疗血吸虫病的新型 smHDAC8 抑制剂的合成、构效关系、共结晶和细胞表征

  摘要：

  血吸虫病是一种被忽视的主要寄生虫病，影响全球超过 2.65 亿人，其控制策略包括使用唯一可用的药物吡喹酮进行大规模治疗。在这项研究中，我们对我们之前报道的基于苯甲羟肟酸盐的曼氏血吸虫组蛋白脱乙酰酶 8 (smHDAC8) 抑制剂进行了化学优化。晶体学分析提供了对高效抑制剂5o对 smHDAC8 活性的抑制模式的见解. 使用可用的晶体结构以及对 smHDAC8 的对接研究对新型抑制剂进行了基于结构的优化。在筛选中评估了这些化合物对血吸虫和人类 HDAC (hHDAC) 的抑制活性。体外和对接结果用于详细的结构活性关系。使用基于荧光的测定法进一步研究合成的化合物对血吸虫幼虫阶段的杀伤力。最有希望的抑制剂5o显示出显着的剂量依赖性杀死血吸虫幼虫和显着损害培养中的成虫对的产卵。

  DOI：

  10.1016/j.ejmech.2021.113745

文献信息

• CYCLIC TRIAZO AND DIAZO SODIUM CHANNEL BLOCKERS
  申请人：University of Greenwich

  公开号：US20140155403A1

  公开（公告）日：2014-06-05

  A method of treating a disorder. The method includes administering to a subject in need thereof a compound of formula (I): Each of A, N*, X, Y, Z, R1, and R2 is defined herein. Also disclosed are compounds of the formula and a pharmaceutical composition containing such a compound.

  一种治疗疾病的方法。该方法包括向需要治疗的受试者施用式（I）的化合物：其中A、N*、X、Y、Z、R1和R2均在此定义。还公开了该式的化合物和包含该化合物的制药组合物。
• Generation of Monospecific Nanomolar Tyrosine Kinase Inhibitors via a Chemical Genetic Approach
  作者：Anthony C. Bishop、Chi-yun Kung、Kavita Shah、Laurie Witucki、Kevan M. Shokat、Yi Liu

  DOI：10.1021/ja983267v

  日期：1999.2.1

  Selective protein kinase inhibitors are highly sought after as tools for studying cellular signal transduction cascades, yet few have been discovered due to the highly conserved fold of kinase catalytic domains. Through a combination of small molecule synthesis and protein mutagenesis, a highly potent (IC50 = 1.5 nM) and uniquely specific inhibitor (4-amino-1-tert-butyl-3-(1'-naphthyl)pyrazolo[3,4-d]pyrimidine) of a rationally engineered v-Src tyrosine kinase (Ile338Gly v-Src) has been identified. Both the potency and specificity of this compound surpass those of any known Src family tyrosine kinase inhibitors. The molecule strongly inhibits the engineered v-Src in whole cells but does not inhibit tyrosine phosphorylation in cells that express only wild-type tyrosine kinases. In addition, the inhibitor selectively disrupts transformation in cells that express the target v-Src. The structural degeneracy of kinase active sites should allow the same complementary inhibitor/protein design strategy to be widely applicable across this entire enzyme superfamily.
• US9422253B2
  申请人：——

  公开号：US9422253B2

  公开（公告）日：2016-08-23
• US9862691B2
  申请人：——

  公开号：US9862691B2

  公开（公告）日：2018-01-09
• Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii
  作者：Sebastian Lourido、Chao Zhang、Michael S. Lopez、Keliang Tang、Jennifer Barks、Qiuling Wang、Scott A. Wildman、Kevan M. Shokat、L. David Sibley

  DOI：10.1021/jm4001314

  日期：2013.4.11

  Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.