6-Isopropyl-4-oxo-4H-chromene-3-carboxylic acid | 76743-80-1

• 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: 6-Isopropyl-4-oxo-4H-chromene-3-carboxylic acid
• 英文别名: 4-Oxo-6-propan-2-ylchromene-3-carboxylic acid
• CAS: 76743-80-1
• 化学式: C₁₃H₁₂O₄
• 分子量: 232.236
• InChiKey: YYWGZBVBYNWDQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  368.1±42.0 °C(Predicted)
• 密度：
  1.308±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-Isopropyl-4-oxo-4H-chromene-3-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 生成 methyl 6-isopropyl-4-oxo-4H-chromene-3-carboxylate
  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：

  1-[2-羟基-5-(1-甲基乙基)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 6-Isopropyl-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

• Asymmetric construction of six vicinal stereogenic centers on hexahydroxanthones <i>via</i> organocatalytic one-pot reactions
  作者：Min Zhang、Xue-Wen He、Ya Xiong、Xiong Zuo、Wei Zhou、Xiong-Li Liu

  DOI：10.1039/d1cc02570h

  日期：——

  herein we report an organocatalytic Michael–Michael–Aldol-decarboxylation reaction that provides efficient access to biologically interesting fully substituted hexahydroxanthones bearing six contiguous stereogenic centers from readily accessible materials in acceptable yields (up to 63%) and excellent stereoselectivities (up to 10 : 1 dr and >99% ee). In other words, the reaction efficiently produces

  受六氢氧杂蒽酮的化学和生物学的启发，我们在此报告了一种有机催化迈克尔-迈克尔-羟醛脱羧反应，该反应可以有效地从易于获得的材料中以可接受的产率（高达 63%）获得带有六个连续立体中心的具有生物学意义的完全取代的六氢氧杂蒽酮。和出色的立体选择性（高达 10 : 1 dr 和 >99% ee）。换句话说，该反应在一锅操作中有效地产生了三个化学键和多达六个邻位立体中心。特别是，据我们所知，这是一种不对称的有机催化策略，能够在非螺环六氢氧杂蒽酮骨架上首次构建六个邻位立体中心。
• 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.