8-Methoxy-4-oxochromene-3-carbonyl chloride | 53813-02-8

• 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-oxochromene-3-carbonyl chloride
• CAS: 53813-02-8
• 化学式: C₁₁H₇ClO₄
• 分子量: 238.627
• InChiKey: FKJPLURBMWDOQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-Methoxy-4-oxochromene-3-carbonyl chloride 在 copper(l) iodide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.5h， 生成
  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：

  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

文献信息

• US3937837A
  申请人：——

  公开号：US3937837A

  公开（公告）日：1976-02-10
• 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。