Methyl 6-methoxy-4-oxo-4H-chromene-3-carboxylate | 105508-58-5

• 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: Methyl 6-methoxy-4-oxo-4H-chromene-3-carboxylate
• 英文别名: methyl 6-methoxy-4-oxochromene-3-carboxylate
• CAS: 105508-58-5
• 化学式: C₁₂H₁₀O₅
• 分子量: 234.208
• InChiKey: GAPQDKQICVMUOC-UHFFFAOYSA-N

物化性质

• 沸点：
  370.1±42.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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 6-methoxy-4-oxo-4H-chromene-3-carboxylate 在 sodium hydroxide 、 copper(l) iodide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 7.25h， 生成 2-benzo[1,3]dioxol-5-yl-4-butoxy-6-methoxy-2H-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
• 作为产物：
  描述：

  2'-羟基-5'-甲氧基苯乙酮 在 sodium chlorite 、 氨基磺酸 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 Methyl 6-methoxy-4-oxo-4H-chromene-3-carboxylate
  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

文献信息

• Synthesis of 2-substituted chromones, chromanones, and their thio analogues using organocopper reagents
  作者：Paul D. Clarke、Alan O. Fitton、Hans Suschitzky、Timothy W. Wallace、Hossein A. Dowlatshahi、John L. Suschitzky

  DOI：10.1016/s0040-4039(00)83949-0

  日期：1986.1

  Improved use of organocopper reagents provides a general route to unsymmetrical 2,2-dialkylchomanones and thiochromanones from chromones and thiochromones via a simple addition - oxidation - addition sequence

  改进的有机铜试剂的使用提供了一种通过简单的加成-氧化-加成顺序从色酮和硫代色酮制得不对称的2，2-二烷基苯甲酮和硫代色酮的一般途径。
• CLARKE, P. D.;FITTON, A. O.;SUSCHITZKY, H.;WALLACE, T. W.;DOWLATSHAHI, HO+, TETRAHEDRON LETT., 1986, 27, N 1, 91-94
  作者：CLARKE, P. D.、FITTON, A. O.、SUSCHITZKY, H.、WALLACE, T. W.、DOWLATSHAHI, HO+

  DOI：——

  日期：——