methyl 2-(2-ethoxy-2-oxoethoxy)-3-methylbenzoate | 1616110-77-0

• 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: methyl 2-(2-ethoxy-2-oxoethoxy)-3-methylbenzoate
• 英文别名: Methyl 2-(2-ethoxy-2-oxoethoxy)-3-methylbenzoate
• CAS: 1616110-77-0
• 化学式: C₁₃H₁₆O₅
• 分子量: 252.267
• InChiKey: ULKRSLOYLGWRQE-UHFFFAOYSA-N

物化性质

• 沸点：
  347.4±27.0 °C(Predicted)
• 密度：
  1.143±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(2-ethoxy-2-oxoethoxy)-3-methylbenzoate 在 N-甲基吗啉 、 ammonium hydroxide 、 potassium permanganate 、 ammonium acetate 、 水 、 sodium acetate 、 乙酸酐 、 溶剂黄146 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 20.0h， 生成 (Z)-2-(3,4-dihydroxybenzylidene)-3-oxo-2,3-dihydrobenzofuran-7-carboxamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors

  摘要：

  Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 mu M). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 mu M). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58 (IC50 = 0.531 mu M) showing a 30-fold improvement in potency. Various heterocycles attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 mu M). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.

  DOI：

  10.1021/jm5002502
• 作为产物：
  描述：

  3-甲基水杨酸 在 硫酸 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 methyl 2-(2-ethoxy-2-oxoethoxy)-3-methylbenzoate
  参考文献：
  名称：

  聚（ADP-核糖）聚合酶抑制剂的设计与合成：腺苷口袋结合基序对3-Oxo-2,3-dihydrobenzofuran-7-boxamide的效力和选择性的影响。

  摘要：

  聚腺苷5'-二磷酸核糖）聚合酶（PARP）抑制剂是一类抗癌药物，可阻断PARP蛋白的催化活性。优化我们的先导化合物1（（Z）-2-亚苄基-3-氧代-2,3-二氢苯并呋喃-7-羧酰胺; PARP-1 IC50 = 434 nM）产生了四唑基类似物（51，IC50 = 35 nM）具有更好的抑制作用。用羧基等位取代四唑环（60，IC50 = 68 nM）产生了有希望的新先导，随后对其进行了优化，以获得具有有效PARP-1 IC50值（4-197 nM）的类似物。PARP酶谱分析显示，大多数化合物对PARP-2具有选择性，其IC50值可与临床抑制剂媲美。与PARP-1结合的关键抑制剂的X射线晶体结构说明了与向PARP-1腺苷结合袋延伸的类似附件的相互作用方式。化合物81，一种同工型选择性PARP-1 / -2（IC50 = 30 nM / 2 nM）抑制剂，与同基因BRCA1精制细胞相比，对乳腺

  DOI：

  10.1021/acs.jmedchem.8b01709

文献信息

• [EN] SUBSTITUTED DIHYDROINDENE-4-CARBOXAMIDES AND ANALOGS THEREOF, AND METHODS USING SAME<br/>[FR] DIHYDROINDÈNE-4-CARBOXAMIDES SUBSTITUÉS, LEURS ANALOGUES ET PROCÉDÉS D'UTILISATION CORRESPONDANT
  申请人：ARBUTUS BIOPHARMA CORP

  公开号：WO2018172852A1

  公开（公告）日：2018-09-27

  The present invention includes novel substituted bicyclic compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infections in a patient. In certain embodiments, the compounds and compositions of the invention are capsid inhibitors. (Formula I)

  本发明包括新颖的取代双环化合物，以及包含这些化合物的组合物，可用于治疗或预防患者体内的乙型肝炎病毒（HBV）感染。在某些实施例中，本发明的化合物和组合物是壳蛋白抑制剂。（化学式I）
• 一种作为IRAK抑制剂的化合物
  申请人：上海美悦生物科技发展有限公司

  公开号：CN111560012B

  公开（公告）日：2023-06-23

  本发明涉及适用于治疗癌症和与白细胞介素‑1受体相关激酶(IRAK)相关的炎性疾病的化合物，具体地是一种作为IRAK4抑制剂的化合物及其制备方法和用途，更具体地是式(I)所示的化合物、其立体异构体、消旋体、互变异构体、同位素标记物、氮氧化物或其药学上可接受的盐及其制备方法和用途。本发明中所披露的化合物对IRAK4激酶有良好的抑制作用，并且对其他激酶具有良好的选择性。
• SUBSTITUTED DIHYDROINDENE-4-CARBOXAMIDES AND ANALOGS THEREOF, AND METHODS USING SAME
  申请人：Arbutus Biopharma Corporation

  公开号：EP3601216A1

  公开（公告）日：2020-02-05
• Discovery of Potent Isoindolinone Inhibitors that Target an Active Conformation of PARP1 Using DNA‐Encoded Libraries
  作者：Kelly A. McCarthy、Douglas J. Marcotte、Sangram Parelkar、Crystal L. McKinnon、Lindsay E. Trammell、Eric L. Stangeland、Rachael R. Jetson

  DOI：10.1002/cmdc.202400093

  日期：——

  Inhibition of poly (ADP‐ribose) polymerase‐1 (PARP1), a DNA repair enzyme, has proven to be a successful strategy for the treatment of various cancers. With the appropriate selection conditions and protein design, DNA‐encoded library (DEL) technology provides a powerful avenue to identify small molecules with the desired mechanism of action towards a target of interest. However, DNA‐binding proteins, such as PARP1, can be challenging targets for DEL screening due to non‐specific protein−DNA interactions. To overcome this, we designed and screened a PARP1 catalytic domain construct without the autoinhibitory helical domain. This allowed us to interrogate an active, functionally‐relevant form of the protein resulting in the discovery of novel isoindolinone PARP1 inhibitors with single‐digit nanomolar potency. These inhibitors also demonstrated little to no PARP1−DNA trapping, a property that could be advantageous in the clinic.
• Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity
  作者：Uday Kiran Velagapudi、Marie-France Langelier、Cristina Delgado-Martin、Morgan E. Diolaiti、Sietske Bakker、Alan Ashworth、Bhargav A. Patel、Xuwei Shao、John M. Pascal、Tanaji T. Talele

  DOI：10.1021/acs.jmedchem.8b01709

  日期：2019.6.13

  Poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitors are a class of anticancer drugs that block the catalytic activity of PARP proteins. Optimization of our lead compound 1 (( Z)-2-benzylidene-3-oxo-2,3-dihydrobenzofuran-7-carboxamide; PARP-1 IC50 = 434 nM) led to a tetrazolyl analogue (51, IC50 = 35 nM) with improved inhibition. Isosteric replacement of the tetrazole ring with a carboxyl

  聚腺苷5'-二磷酸核糖）聚合酶（PARP）抑制剂是一类抗癌药物，可阻断PARP蛋白的催化活性。优化我们的先导化合物1（（Z）-2-亚苄基-3-氧代-2,3-二氢苯并呋喃-7-羧酰胺; PARP-1 IC50 = 434 nM）产生了四唑基类似物（51，IC50 = 35 nM）具有更好的抑制作用。用羧基等位取代四唑环（60，IC50 = 68 nM）产生了有希望的新先导，随后对其进行了优化，以获得具有有效PARP-1 IC50值（4-197 nM）的类似物。PARP酶谱分析显示，大多数化合物对PARP-2具有选择性，其IC50值可与临床抑制剂媲美。与PARP-1结合的关键抑制剂的X射线晶体结构说明了与向PARP-1腺苷结合袋延伸的类似附件的相互作用方式。化合物81，一种同工型选择性PARP-1 / -2（IC50 = 30 nM / 2 nM）抑制剂，与同基因BRCA1精制细胞相比，对乳腺