3,4-二氯苯并[B]噻吩-2-甲酰氯 | 34576-86-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 3,4-二氯苯并[B]噻吩-2-甲酰氯
• 中文别名: 3,4-二氯苯并[b]噻吩-2-甲酰氯
• 英文名称: 3,4-Dichlor-benzo--thiophen-2-carbonsaeurechlorid
• 英文别名: 3,4-dichlorobenzo[b]thiophene-2-carbonyl chloride；2-Chlorcarbonyl-3,4-dichlorbenzothiophen；3,4-Dichloro-1-benzothiophene-2-carbonyl chloride
• CAS: 34576-86-8
• 化学式: C₉H₃Cl₃OS
• mdl: MFCD01993638
• 分子量: 265.547
• InChiKey: FABCCQHAVXFNMK-UHFFFAOYSA-N

物化性质

• 熔点：
  143 °C
• 沸点：
  375.0±37.0 °C(Predicted)
• 密度：
  1.625±0.06 g/cm3(Predicted)
• 稳定性/保质期：
  如果按照规格使用和储存，则不会分解，未有已知危险反应。应避免与氧化物、水分等接触。

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  45.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  8
• 海关编码：
  2934999090
• 包装等级：
  III
• 危险类别：
  8
• 危险品运输编号：
  UN3261

反应信息

• 作为反应物：
  描述：

  3,4-二氯苯并[B]噻吩-2-甲酰氯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 、 lithium hydroxide 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 生成 tert-butyl ((2R,6S,13aS,14aR,16aS,Z)-14a-((cyclopropylsulfonyl)carbamoyl)-2-(3,4-dichlorobenzo[b]thiophene-2-carboxamido)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate
  参考文献：
  名称：

  Discovery of Danoprevir (ITMN-191/R7227), a Highly Selective and Potent Inhibitor of Hepatitis C Virus (HCV) NS3/4A Protease

  摘要：

  HCV serine protease NS3 represents an attractive drug target because it is not only essential for viral replication but also implicated in the viral evasion of the host immune response pathway through direct cleavage of key proteins in the human innate immune system. Through structure-based drug design and optimization, macrocyclic peptidomimetic molecules bearing both a lipophilic P2 isoindoline carbamate and a Pl/P1' acylsulfonamide/acylsulfamide carboxylic acid bioisostere were prepared that possessed subnanomolar potency against the NS3 protease in a subgenomic replicon-based cellular assay (Huh-7). Danoprevir (compound 49) was selected as the clinical development candidate for its favorable potency profile across multiple HCV genotypes and key mutant strains and for its good in vitro ADME profiles and in vivo target tissue (liver) exposures across multiple animal species. X-ray crystallographic studies elucidated several key features in the binding of danoprevir to HCV NS3 protease and proved invaluable to our iterative structure-based design strategy.

  DOI：

  10.1021/jm400164c
• 作为产物：
  描述：

  邻氯肉桂酸 在 吡啶 、 氯化亚砜 作用下， 反应 3.0h， 生成 3,4-二氯苯并[B]噻吩-2-甲酰氯
  参考文献：
  名称：

  有望成为一类抗菌剂的苯并[b]噻吩衍生物的合成，表征及结构活性关系的研究

  摘要：

  在这里，我们采用简单的化学方法，通过以下方法合成了一系列新的强效的苯并[b]噻吩系列化合物：2-羰基氯化物（1），2-异丙基羧酰胺（2），2-（哌啶-1-基）-甲酮（3）。取代肉桂酸与亚硫酰氯的亲核氯环缩合，得到苯并[b]噻吩核。产品的组成已通过元素分析和光谱分析进行了描述。测定产品在不同浓度下的体外抗菌试验，并与可用的标准药物氨苄西林，氯霉素，环丙沙星，诺氟沙星和灰黄霉素进行比较。还研究了合成化合物的结构活性关系。标题化合物的初步体外生物学筛选显示，化合物2b，2c，2e，

  DOI：

  10.2174/15701808113106660091

文献信息

• Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors
  作者：Chao Che、Song Li、Bo Yang、Shengchang Xin、Zhixiong Yu、Taofeng Shao、Chuanye Tao、Shuo Lin、Zhen Yang

  DOI：10.3762/bjoc.8.94

  日期：——

  Sant-75 is a newly identified potent inhibitor of the hedgehog pathway. We designed a diversity-oriented synthesis program, and synthesized a series of Sant-75 analogues, which lays the foundation for further investigation of the structure–activity relationship of this important class of hedgehog-pathway inhibitors.

  Sant-75是一种新发现的对刺猬途径具有强大抑制作用的抑制剂。我们设计了一个多样性定向合成计划，并合成了一系列Sant-75类似物，为进一步研究这一重要类别的刺猬途径抑制剂的结构-活性关系奠定了基础。
• ——
  作者：N. D. Obushak、V. S. Matiichuk、R. L. Martyak

  DOI：10.1023/a:1026190103546

  日期：——
• Potent small molecule Hedgehog agonists induce VEGF expression in vitro
  作者：Katrin Seifert、Anita Büttner、Stephan Rigol、Nicole Eilert、Elke Wandel、Athanassios Giannis

  DOI：10.1016/j.bmc.2012.08.026

  日期：2012.11

  Here, we describe the synthesis, SAR studies as well as biological investigations of the known Hedgehog signaling agonist SAG and a small library of its analogues. The SAG and its derivatives were analyzed for their potency to activate the expression of the Hh target gene Gli1 in a reporter gene assay. By analyzing SAR important molecular descriptors for Gill activation have been identified. SAG as well as compound 10c proven to be potent activators of VEGF expression in cultivated dermal fibroblasts. Importantly and in contrast to SAG, derivative 10c displayed no toxicity in concentrations up to 250 mu m. (C) 2012 Elsevier Ltd. All rights reserved.
• Ried, Walter; Oremek, Gerhard; Ocakcioglu, Belkis, Liebigs Annalen der Chemie, 1980, # 9, p. 1424 - 1427
  作者：Ried, Walter、Oremek, Gerhard、Ocakcioglu, Belkis

  DOI：——

  日期：——
• De-Novo Design of Cereblon (CRBN) Effectors Guided by Natural Hydrolysis Products of Thalidomide Derivatives
  作者：Christopher Heim、Dimanthi Pliatsika、Farnoush Mousavizadeh、Kerstin Bär、Birte Hernandez Alvarez、Athanassios Giannis、Marcus D. Hartmann

  DOI：10.1021/acs.jmedchem.9b00454

  日期：2019.7.25

  Targeted protein degradation via cereblon (CRBN), a substrate receptor of an E3 ubiquitin ligase complex, is an increasingly important strategy in various clinical settings, in which the substrate specificity of CRBN is altered via the binding of small-molecule effectors. To date, such effectors are derived from thalidomide and confer a broad substrate spectrum that is far from being fully characterized. Here, we employed a rational and modular approach to design novel and minimalistic CRBN effectors. In this approach, we took advantage of the binding modes of hydrolyzed metabolites of several thalidomide-derived effectors, which we elucidated via crystallography. These yielded key insights for the optimization of the minimal core binding moiety and its linkage to a chemical moiety that imparts substrate specificity. Based on this scaffold, we present a first active de-novo CRBN effector that is able to degrade the neo-substrate IKZF3 in the cell culture.