5-bromomethyl-thiophene-3-carboxylic acid ethyl ester | 206860-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-bromomethyl-thiophene-3-carboxylic acid ethyl ester
• 英文别名: ethyl 5-(bromomethyl)thiophene-3-carboxylate
• CAS: 206860-16-4
• 化学式: C₈H₉BrO₂S
• 分子量: 249.128
• InChiKey: ALEIYHHZQWQKRE-UHFFFAOYSA-N

物化性质

• 沸点：
  307.4±32.0 °C(Predicted)
• 密度：
  1.530±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromomethyl-thiophene-3-carboxylic acid ethyl ester 在 palladium on activated charcoal lithium hydroxide 、 sodium azide 、 氢气 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~50.0 ℃ 、206.84 kPa 条件下， 反应 3.5h， 生成 5-(氨基甲基)-3-噻吩羧酸
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j
• 作为产物：
  描述：

  ((4-bromothiophene-2-yl)methoxy)(tert-butyl)dimethylsilane 在 正丁基锂 、 四溴化碳 、 四丁基氟化铵 、 溶剂黄146 、 三苯基膦 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 15.0h， 生成 5-bromomethyl-thiophene-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j

文献信息

• Synthesis and Evaluation of the First Fluorescent Antagonists of the Human P2Y₂ Receptor Based on AR-C118925
  作者：Sean Conroy、Nicholas D. Kindon、Jacqueline Glenn、Leigh A. Stoddart、Richard J. Lewis、Stephen J. Hill、Barrie Kellam、Michael J. Stocks

  DOI：10.1021/acs.jmedchem.8b00139

  日期：2018.4.12

  The human P2Y2 receptor ( hP2Y2R) is a G-protein-coupled receptor that shows promise as a therapeutic target for many important conditions, including for antimetastatic cancer and more recently for idiopathic pulmonary fibrosis. As such, there is a need for new hP2Y2R antagonists and molecular probes to study this receptor. Herein, we report the development of a new series of non-nucleotide hP2Y2R

  人P2Y2受体（hP2Y2R）是一种G蛋白偶联受体，显示出有望作为许多重要疾病（包括抗转移性癌症以及最近用于特发性肺纤维化）的治疗靶标。因此，需要新的hP2Y2R拮抗剂和分子探针来研究该受体。本文中，我们报告了基于已知的非核苷酸hP2Y2R拮抗剂AR-C118925（1）的新系列非核苷酸hP2Y2R拮抗剂的开发，从而发现了一系列包含不同接头和荧光团的荧光配体。这些缀合物之一98在生物发光能量转移（BRET）分析中显示出对hP2Y2R的微摩尔亲和力（p Kd = 6.32±0.10，n = 17）。用该配体的共聚焦显微镜显示表达未标记hP2Y2R的星形细胞瘤细胞的可置换膜标记。这些特性使98成为研究hP2Y2R分布和组织的首批工具之一。
• TLR7 AGONISTS
  申请人：Primmune Therapeutics, Inc.

  公开号：EP3801538A1

  公开（公告）日：2021-04-14