7-苯并呋喃甲酰胺2,3-二氢-3氧代 | 1616110-80-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 中文名称: 7-苯并呋喃甲酰胺2,3-二氢-3氧代
• 英文名称: 3-oxo-2,3-dihydrobenzofuran-7-carboxamide
• 英文别名: 7-Benzofurancarboxamide, 2,3-dihydro-3-oxo-；3-oxo-1-benzofuran-7-carboxamide
• CAS: 1616110-80-5
• 化学式: C₉H₇NO₃
• 分子量: 177.159
• InChiKey: XHAYQYHWMQRNRK-UHFFFAOYSA-N

物化性质

• 沸点：
  342.7±42.0 °C(Predicted)
• 密度：
  1.419±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  69.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-苯并呋喃甲酰胺2,3-二氢-3氧代 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 ammonium acetate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 0.25h， 生成 (Z)-2-(2-(4-((7-carbamoyl-3-oxobenzofuran-2(3H)-ylidene)methyl)benzamido)ethyl)-1H-benzo[d]imidazole-4-carboxamide
  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
• 作为产物：
  描述：

  3-甲基水杨酸 在 N-甲基吗啉 、 盐酸 、 potassium permanganate 、 硫酸 、 potassium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 99.5h， 生成 7-苯并呋喃甲酰胺2,3-二氢-3氧代
  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

• CONJUGATES OF PORPHYRINOID PHOTOSENSITIZERS AND GLYCEROL-BASED POLYMERS FOR PHOTODYNAMIC THERAPY
  申请人：biolitec Unternehmensbeteiligungs II AG

  公开号：EP3210626A1

  公开（公告）日：2017-08-30

  Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. In addition, conjugates are provided in which these photosensitizers are attached to water-soluble polymers via cleavable linkers that can be cleaved in the body under specific conditions. Another embodiment consists of formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.

  本发明提供了可用作诊断和治疗用光敏剂的生物活性化合物，特别是用于癌症、感染和其他过度增殖性疾病的PDT、荧光诊断和关节炎、炎症性疾病、病毒或细菌感染、皮肤病、眼科或泌尿科疾病等非肿瘤适应症的PDT治疗，并提供了以药品质量获得这些光敏剂的方法。此外，还提供了共轭物，其中这些光敏剂通过可裂解连接体附着在水溶性聚合物上，可在特定条件下在体内裂解。另一个实施方案是将所需的四吡咯光敏剂配制成药物制剂注入体内，以避免四吡咯系统的溶解性问题或药代动力学延迟等不良影响。
• Conjugates of porphyrinoid photosensitizers and glycerol-based polymers for photodynamic therapy
  申请人：biolitec Unternehmensbeteiligungs II AG

  公开号：US10738059B2

  公开（公告）日：2020-08-11

  Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. In addition, conjugates are provided in which these photosensitizers are attached to water-soluble polymers via cleavable linkers that can be cleaved in the body under specific conditions. Another embodiment consists of formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.

  本发明提供了可用作诊断和治疗用光敏剂的生物活性化合物，特别是用于癌症、感染和其他过度增殖性疾病的PDT、荧光诊断和关节炎、炎症性疾病、病毒或细菌感染、皮肤病、眼科或泌尿科疾病等非肿瘤适应症的PDT治疗，并提供了以药品质量获得这些光敏剂的方法。此外，还提供了共轭物，其中这些光敏剂通过可裂解连接体附着在水溶性聚合物上，可在特定条件下在体内裂解。另一个实施方案是将所需的四吡咯光敏剂配制成药物制剂注入体内，以避免四吡咯系统的溶解性问题或药代动力学延迟等不良影响。
• Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2<i>H</i>)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors
  作者：Maulik R. Patel、Aaditya Bhatt、Jamin D. Steffen、Adel Chergui、Junko Murai、Yves Pommier、John M. Pascal、Louis D. Trombetta、Frank R. Fronczek、Tanaji T. Talele

  DOI：10.1021/jm5002502

  日期：2014.7.10

  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.
• 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