8-methoxy-4-oxo-4H-chromene-3-carboxylic acid | 59157-78-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-methoxy-4-oxo-4H-chromene-3-carboxylic acid
• 英文别名: 8-methoxy-4-oxochromene-3-carboxylic acid
• CAS: 59157-78-7
• 化学式: C₁₁H₈O₅
• 分子量: 220.182
• InChiKey: QUADPQBDTZPKMM-UHFFFAOYSA-N

物化性质

• 沸点：
  398.5±42.0 °C(Predicted)
• 密度：
  1.454±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 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：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-methoxy-4-oxo-4H-chromene-3-carboxylic acid 在 氯化亚砜 作用下， 生成 8-Methoxy-4-oxochromene-3-carbonyl chloride
  参考文献：
  名称：

  通过铜双（恶唑啉）催化的 [4 + 2] 环加成对映选择性获得四氢氧蒽酮

  摘要：

  通过铜双（恶唑啉）催化的 chrom-4-one 亲二烯体和 Danishefsky 的二烯的 [4 + 2] 环加成反应，实现了对四氢氧杂蒽酮化合物的高度对映选择性。含四元立构中心的氧代二氢氧吨酮（烯酮）加合物的产率高达 98%，ee 高达 89%。环加合物用于合成四氢氧吨酮，具有新型有机锡介导的 β-酮酯准 Krapcho 脱羧作用，并保留立体化学。Tetrahydroxanthone 是多种生物相关饱和氧杂蒽酮的多功能中间体。

  DOI：

  10.1021/acs.orglett.3c00612
• 作为产物：
  描述：

  1-(2-羟基-3-甲氧苯基)乙酮 在 sodium chlorite 、 氨基磺酸 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 8-methoxy-4-oxo-4H-chromene-3-carboxylic acid
  参考文献：
  名称：

  Structure−Activity Relationships of a Novel Class of Endothelin-A Receptor Antagonists and Discovery of Potent and Selective Receptor Antagonist, 2-(Benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4-(4-methoxyphenyl)-2H-chromene-3- carboxylic Acid (S-1255). 1. Study on Structure−Activity Relationships and Basic Structure Crucial for ET_A Antagonism

  摘要：

  A novel series of endothelin-A (ETA) selective receptor antagonists having a 2H-chromene skeleton are described. A lead compound, 2-(benzo[1,3]dioxol-5-yl)-2H-chromene-3-carboxylic acid (3), was found by modifications of our own angiotensin II antagonist. A structure-activity relationship (SAR) study of 3 reveals that the structural requirements essential for potent and selective ETA receptor binding affinity are the m,p-methylenedioxyphenyl, carboxyl, and isopropoxy groups at the 2-, 3-, and 6-positions, respectively, on the (R)-2H-chromene skeleton. The substituent at the 4-position is also important for improving the activity, and various hydrophobic functional groups of 6-9 Angstrom such as liner, branched, and cyclic aliphatic groups, unsubstituted and substituted aryl groups, and even halogen atoms were acceptable. These results suggest that (R)-2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-2H-chromene-3-carboxylic acid, formula 108, is the crucial basic structure to be recognized by the ETA receptor. The most potent compound is (R)-48 (S-1255), which binds to the ETA receptor with an IC50 value of 0.19 nM and is 630-fold selective for the ETA receptor than for the ETB receptor. This compound has 55% oral bioavailability in rats. On the basis of the SAR, the roles of each substituent in the receptor binding are discussed.

  DOI：

  10.1021/jm010382z

文献信息

• Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit
  作者：Brian S. Gerstenberger、John D. Trzupek、Cynthia Tallant、Oleg Fedorov、Panagis Filippakopoulos、Paul E. Brennan、Vita Fedele、Sarah Martin、Sarah Picaud、Catherine Rogers、Mihir Parikh、Alexandria Taylor、Brian Samas、Alison O’Mahony、Ellen Berg、Gabriel Pallares、Adam D. Torrey、Daniel K. Treiber、Ivan J. Samardjiev、Brian T. Nasipak、Teresita Padilla-Benavides、Qiong Wu、Anthony N. Imbalzano、Jeffrey A. Nickerson、Mark E. Bunnage、Susanne Müller、Stefan Knapp、Dafydd R. Owen

  DOI：10.1021/acs.jmedchem.6b00012

  日期：2016.5.26

  modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding mode of a phenolic headgroup that led to the unusual displacement of water molecules

  在选定的组蛋白赖氨酸残基上的染色质的乙酰基翻译后修饰是通过与溴结构域阅读器模块的乙酰基赖氨酸特异性相互作用来解释的。在这里，我们报告发现一种有效的，与乙酰赖氨酸竞争的，具有细胞活性的抑制剂PFI-3，该抑制剂与某些VIII族溴结构域结合，同时显示出显着的，更广泛的溴结构域家族选择性。PFI-3对VIII族的高特异性是通过酚类头基的新型溴结构域结合模式实现的，该模式导致水分子异常移位，而水分子通常被迄今报道的大多数其他溴结构域抑制剂保留。详细描述了从最初的片段筛选击中导致PFI-3的药物化学程序，还报道了具有不同的VIII族溴结构域选择性分布的其他类似物。我们还描述了作为化学探针的PFI-3的完整药理特性，以及脂肪细胞和成肌细胞分化试验的表型数据。
• US4196128A
  申请人：——

  公开号：US4196128A

  公开（公告）日：1980-04-01
• Structure−Activity Relationships of a Novel Class of Endothelin-A Receptor Antagonists and Discovery of Potent and Selective Receptor Antagonist, 2-(Benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4-(4-methoxyphenyl)-2<i>H</i>-chromene-3- carboxylic Acid (S-1255). 1. Study on Structure−Activity Relationships and Basic Structure Crucial for ET_A Antagonism
  作者：Natsuki Ishizuka、Ken-ichi Matsumura、Katsunori Sakai、Masafumi Fujimoto、Shin-ichi Mihara、Teruo Yamamori

  DOI：10.1021/jm010382z

  日期：2002.5.1

  A novel series of endothelin-A (ETA) selective receptor antagonists having a 2H-chromene skeleton are described. A lead compound, 2-(benzo[1,3]dioxol-5-yl)-2H-chromene-3-carboxylic acid (3), was found by modifications of our own angiotensin II antagonist. A structure-activity relationship (SAR) study of 3 reveals that the structural requirements essential for potent and selective ETA receptor binding affinity are the m,p-methylenedioxyphenyl, carboxyl, and isopropoxy groups at the 2-, 3-, and 6-positions, respectively, on the (R)-2H-chromene skeleton. The substituent at the 4-position is also important for improving the activity, and various hydrophobic functional groups of 6-9 Angstrom such as liner, branched, and cyclic aliphatic groups, unsubstituted and substituted aryl groups, and even halogen atoms were acceptable. These results suggest that (R)-2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-2H-chromene-3-carboxylic acid, formula 108, is the crucial basic structure to be recognized by the ETA receptor. The most potent compound is (R)-48 (S-1255), which binds to the ETA receptor with an IC50 value of 0.19 nM and is 630-fold selective for the ETA receptor than for the ETB receptor. This compound has 55% oral bioavailability in rats. On the basis of the SAR, the roles of each substituent in the receptor binding are discussed.
• Enantioselective Access to Tetrahydroxanthones via Copper-<i>bis</i>(oxazoline)-Catalyzed [4 + 2] Cycloaddition
  作者：Jonathan W. Attard、Julia R. Noel、Yong Guan、Anita E. Mattson

  DOI：10.1021/acs.orglett.3c00612

  日期：2023.4.14

  Highly enantioselective access to tetrahydroxanthone compounds was achieved through copper-bis(oxazoline)-catalyzed [4 + 2] cycloaddition of chrom-4-one dienophiles and Danishefsky’s diene. Oxo-dihydroxanthone (enone) adducts, containing a quaternary stereocenter, are generated in up to 98% yield and 89% ee. Cycloadducts are utilized in the synthesis of tetrahydroxanthones, featuring a novel organotin-mediated

  通过铜双（恶唑啉）催化的 chrom-4-one 亲二烯体和 Danishefsky 的二烯的 [4 + 2] 环加成反应，实现了对四氢氧杂蒽酮化合物的高度对映选择性。含四元立构中心的氧代二氢氧吨酮（烯酮）加合物的产率高达 98%，ee 高达 89%。环加合物用于合成四氢氧吨酮，具有新型有机锡介导的 β-酮酯准 Krapcho 脱羧作用，并保留立体化学。Tetrahydroxanthone 是多种生物相关饱和氧杂蒽酮的多功能中间体。