2-(7-羟基-2-氧代-2H-苯并吡喃-4-基)乙酰胺 | 101999-45-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 2-(7-羟基-2-氧代-2H-苯并吡喃-4-基)乙酰胺
• 英文名称: 2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetamide
• 英文别名: 2-[7-hydroxy-2-oxo-2H-chromen-4-yl]acetamide；7-hydroxycoumarin-4-acetamide；4-[(aminocarbonyl)methyl]-7-hydroxy-2H-chromen-2-one；7-hydroxy-2-oxo-2H-1-benzopyran-4-acetamide；2-(7-hydroxy-2-oxochromen-4-yl)acetamide
• CAS: 101999-45-5
• 化学式: C₁₁H₉NO₄
• mdl: MFCD06001840
• 分子量: 219.197
• InChiKey: YXBOCMCJTKIUAP-UHFFFAOYSA-N

物化性质

• 沸点：
  548.0±50.0 °C(Predicted)
• 密度：
  1.443±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2932209090

反应信息

• 作为反应物：
  描述：

  2-(7-羟基-2-氧代-2H-苯并吡喃-4-基)乙酰胺 在 吡啶 、 盐酸 、 sodium tetrahydroborate 、 三苯基膦 、 三氟乙酸酐 、 cobalt(II) chloride 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 氯仿 、 水 为溶剂， 反应 19.17h， 生成 4-(2-aminoethyl)-7-[(3-chlorobenzyl)oxy]-2H-chromen-2-one hydrochloride
  参考文献：
  名称：

  WO2006/102958

  摘要：

  公开号：
• 作为产物：
  描述：

  1,3-丙酮二羧酸 在 ammonium hydroxide 、 硫酸 作用下， 生成 2-(7-羟基-2-氧代-2H-苯并吡喃-4-基)乙酰胺
  参考文献：
  名称：

  Synthesis and rat lens aldose reductase inhibitory activity of some benzopyran-2-ones

  摘要：

  A number of 4,7-disubstituted benzopyran-2-ones were synthesized and evaluated for crude rat lens aldose reductase inhibitory activity. Substituents on position 4 included CH3, CO2H, CH2CO2H, CH = CHCO2H, and CH2CH2CO2H. The aromatic substituents included OH, OCH3, OCOCH3, CH2CH3, and Cl. Also included in the study were 3-oxo-3H-naphtho[2,1-b]pyran-1-acetic, 2-oxo-2H-naphtho[1,2-b]pyran-4-acetic, and 1-naphthylacetic acids. The benzopyran and naphthopyran derivatives were prepared by the classical von Pechmann reaction. General structure-activity relationships reveal that optimal enzyme inhibitory activity is displayed by those compounds possessing the acetic acid moiety. For example, the most potent derivative, 3-oxo-3H-naphtho[2,1-b]pyran-1-acetic acid with an IC50 of 0.020 microM, is as potent as sorbinil (IC50 = 0.017 microM) in the crude rat lens aldose reductase assay.

  DOI：

  10.1021/jm00156a031

文献信息

• Substituted Aminoalkyl- and Amidoalkyl-Benzopyran Derivatives
  申请人：Carotti Angelo

  公开号：US20090005436A1

  公开（公告）日：2009-01-01

  This invention is related to novel aminoalkyl- and amidoalkyl-benzopyran derivatives of the following general formula (I) wherein: the group is a substituent in position 6 or 7 wherein: R is an aromatic mono- or bi-cyclic carbocyclic ring or a mono- or bi-cyclic heterocyclic ring radical, said rings being optionally substituted by one or two substituents selected from (C 1 -C 5 ) straight or branched alkyl, (C 1 -C 5 ) straight or branched alkoxy, hydroxy, halogen and trifluoromethyl; m is zero or an integer from 1 to 3; n, p, R 1 and R 2 are as herein indicated and R 3 and R 4 are both hydrogen or taken together represent an oxygen atom, and the pharmaceutically acceptable salts thereof. The compounds that are active as selective and reversible MAO-B inhibitors in vitro and in vivo, are useful as medicaments for the prevention and the treatment of CNS degenerative disorders.

  本发明涉及以下通式（I）的新型氨基烷基和酰胺烷基苯并吡喃衍生物： 其中：基团是6或7位的取代基，其中：R是芳香单环或双环碳环或单环或双环杂环基团，所述环可以选择地由一或两个取代基取代，所述取代基选择自（C1-C5）直链或支链烷基，（C1-C5）直链或支链烷氧基，羟基，卤素和三氟甲基；m为零或1至3的整数；n、p、R1和R2如本文所示，而R3和R4均为氢或一起代表氧原子，以及其药学上可接受的盐。 这些化合物在体外和体内作为选择性和可逆的MAO-B抑制剂具有活性，可用作预防和治疗中枢神经系统退行性疾病的药物。
• METHODS FOR ASSAYING ALPHA-L-IDURONIDASE ENZYMATIC ACTIVITY
  申请人：Gelb Michael H.

  公开号：US20100209951A1

  公开（公告）日：2010-08-19

  Methods for assaying α-L-iduronidase enzymatic activity and methods for screening newborns for Mucopolysaccharidosis Type-I.

  α-L-伊杜鲁糖苷酶酶活性检测方法和筛查新生儿粘多糖病I型的方法。
• Dual Inhibitors of Brain Carbonic Anhydrases and Monoamine Oxidase-B Efficiently Protect against Amyloid-β-Induced Neuronal Toxicity, Oxidative Stress, and Mitochondrial Dysfunction
  作者：Simone Giovannuzzi、Daniel Chavarria、Gustavo Provensi、Manuela Leri、Monica Bucciantini、Simone Carradori、Alessandro Bonardi、Paola Gratteri、Fernanda Borges、Alessio Nocentini、Claudiu T. Supuran

  DOI：10.1021/acs.jmedchem.4c00045

  日期：2024.3.14

  We report here the first dual inhibitors of brain carbonic anhydrases (CAs) and monoamine oxidase-B (MAO-B) for the management of Alzheimer’s disease. Classical CA inhibitors (CAIs) such as methazolamide prevent amyloid-β-peptide (Aβ)-induced overproduction of reactive oxygen species (ROS) and mitochondrial dysfunction. MAO-B is also implicated in ROS production, cholinergic system disruption, and

  我们在这里报告了第一个用于治疗阿尔茨海默病的脑碳酸酐酶 (CA) 和单胺氧化酶 -B (MAO-B) 双重抑制剂。经典的 CA 抑制剂 (CAI)，例如醋甲唑胺，可防止淀粉样蛋白-β-肽 (Aβ) 诱导的活性氧 (ROS) 过量产生和线粒体功能障碍。 MAO-B 还与 ROS 产生、胆碱能系统破坏和淀粉样蛋白斑形成有关。在这项工作中，我们将香豆素和色酮类型的可逆 MAO-B 抑制剂与苯磺酰胺片段结合起来作为高效的 CAI。命中先导优化产生了一组重要的衍生物，对目标脑 CA（ K I范围为 0.1–90.0 nM）和 MAO-B（IC 50范围为 6.7– 32.6纳米）。进行计算研究以阐明构效关系并预测 ADMET 特性。在 SH-SY5Y 细胞模型中，最有效的多靶点化合物完全阻止了 Aβ 相关毒性、恢复了 ROS 形成并恢复了线粒体功能，其功效超越了单靶点药物的功效。
• Development of fluorescent peptide substrates and assays for the key autophagy-initiating cysteine protease enzyme, ATG4B
  作者：Lubomir Vezenkov、Nicolette S. Honson、Nag S. Kumar、Damien Bosc、Suzana Kovacic、Thanh G. Nguyen、Tom A. Pfeifer、Robert N. Young

  DOI：10.1016/j.bmc.2015.04.064

  日期：2015.7

  An efficient assay for monitoring the activity of the key autophagy-initiating enzyme ATG4B based on a small peptide substrate has been developed. A number of putative small fluorogenic peptide substrates were prepared and evaluated and optimized compounds showed reasonable rates of cleavage but required high enzyme concentrations which limited their value. A modified peptide substrate incorporating a less sterically demanding self-immolative element was designed and synthesized and was shown to have enhanced properties useful for evaluating inhibitors of ATG4B. Substrate cleavage was readily monitored and was linear for up to 4 h but enzyme concentrations of about ten-fold higher were required compared to assays using protein substrate LC3 or analogs thereof (such as FRET-LC3). Several known inhibitors of ATG4B were evaluated using the small peptide substrate and gave IC50 values 3-7 fold higher than previously obtained values using the FRET-LC3 substrate. (C) 2015 Elsevier Ltd. All rights reserved.
• Discovery of a Novel Class of Potent Coumarin Monoamine Oxidase B Inhibitors: Development and Biopharmacological Profiling of 7-[(3-Chlorobenzyl)oxy]-4-[(methylamino)methyl]-2<i>H</i>-chromen-2-one Methanesulfonate (NW-1772) as a Highly Potent, Selective, Reversible, and Orally Active Monoamine Oxidase B Inhibitor
  作者：Leonardo Pisani、Giovanni Muncipinto、Teresa Fabiola Miscioscia、Orazio Nicolotti、Francesco Leonetti、Marco Catto、Carla Caccia、Patricia Salvati、Ramon Soto-Otero、Estefania Mendez-Alvarez、Celine Passeleu、Angelo Carotti

  DOI：10.1021/jm9010127

  日期：2009.11.12

  In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.