1-(2-hydroxy-6-propoxy-phenyl)-ethanone | 14718-38-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2-hydroxy-6-propoxy-phenyl)-ethanone
• 英文别名: 1-(2-Hydroxy-6-propoxy-phenyl)-aethanon；2-Hydroxy-6-n-propoxyacetophenon；2-Hydroxy-6-propoxyacetophenon；1-(2-Hydroxy-6-propoxyphenyl)ethanone
• CAS: 14718-38-8
• 化学式: C₁₁H₁₄O₃
• 分子量: 194.23
• InChiKey: WPDKEEGSHVJQMW-UHFFFAOYSA-N

物化性质

• 熔点：
  70–71°C
• 沸点：
  303.6±22.0 °C(Predicted)
• 密度：
  1.101±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-hydroxy-6-propoxy-phenyl)-ethanone 在 sodium chlorite 、 草酰氯 、 氨基磺酸 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 1.75h， 生成 Methyl 4-oxo-5-propoxychromene-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：

  2,6-二羟基苯乙酮 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 1-(2-hydroxy-6-propoxy-phenyl)-ethanone
  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

• The synthesis of substituted indazoles<i>via</i>cyclization of various hydrazones in the presence of polyphosphoric acid (PPA)
  作者：Qiu Guofu、Su Jiangtao、Feng Xichun、Wu Lamei、Xu Wenjin、Hu Xianming

  DOI：10.1002/jhet.5570410420

  日期：2004.7

  Research directed toward the discovery of nitric oxide synthase inhibitor led to synthesis of a series of substituted indazoles via the intramolecular cyclization of various hydrazones of substituted acetophenones and benzophenones in the presence of polyphosphoric acid (PPA). The structures of the indazoles were determined by elemental analysis, H nmr, ir, and ms.

  致力于发现一氧化氮合酶抑制剂的研究导致在多磷酸（PPA）存在下，通过取代的苯乙酮和二苯甲酮的各种azo的分子内环化反应，合成了一系列取代的吲唑。吲唑的结构通过元素分析，H nmr，ir和ms确定。
• CHROMENE-3-CARBOXYLATE DERIVATIVES
  申请人：SHIONOGI & CO., LTD.

  公开号：EP0924207A1

  公开（公告）日：1999-06-23

  The present invention provides a compound of the formula (I): wherein R1, R2, R3 and R4 are each independently hydrogen, optionally substituted alkyl, hydroxy, optionally substituted alkoxy or the like, R5 is optionally substituted alkyl, optionally substituted aryl, optionally substituted heterocyclic or the like, R6 is hydrogen, optionally substituted alkyl or the like, R7 is hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heterocyclic or the like, A is S or O and a broken line represents presence or absence of a bond, pharmaceutically acceptable salt or hydrate thereof and a pharmaceutical composition or a pharmaceutical composition for use as an endothelin receptor antagonist, a peripheral circulation insufficiency-improving agent or a macrophage foam cell formation inhibitor comprising the compound.

  本发明提供了式 (I) 的化合物： 其中 R1、R2、R3 和 R4 各自独立地是氢、任选取代的烷基、羟基、任选取代的烷氧基或类似物，R5 是任选取代的烷基、任选取代的芳基、任选取代的杂环或类似物，R6 是氢、任选取代的烷基或类似物，R7 是氢、任选取代的烷基、任选取代的烷氧基、任选取代的芳基、任选取代的杂环或类似物，A 是 S 或 O，断线表示存在或不存在键、 其药学上可接受的盐或水合物，以及包含该化合物的用作内皮素受体拮抗剂、外周循环不全改善剂或巨噬细胞泡沫形成抑制剂的药物组合物或药物组合物。
• PROCESS FOR PRODUCING OPTICALLY ACTIVE CHROMENE DERIVATIVE
  申请人：SHIONOGI & CO., LTD.

  公开号：EP1057824A1

  公开（公告）日：2000-12-06

  A process for producing a compound of the formula (II): wherein R1, R2, R3 and R4 are each independently e.g. hydrogen, alkyl or alkoxy, R5 is alkyl or alkoxyalkyl, A is 0 or S, Ar is aryl, * represents the position of an asymmetric carbon atom and the compound is the (R) or (S) isomer and Q is an optical resolution reagent, comprising isolating the compound as crystals from a solution or suspension containing the compound of the formula (II) wherein * represents that the compound is the (R) or (S) isomer or a mixture thereof and the other symbols are the same as above.

  一种生产式(II)化合物的工艺： 其中 R1、R2、R3 和 R4 各自独立地例如为氢、烷基或烷氧基，R5 为烷基或烷氧基烷基，A 为 0 或 S，Ar 为芳基，* 代表不对称碳原子的位置，且该化合物为 (R) 或 (S) 异构体，Q 为光学分解试剂，包括从含有式 (II) 化合物的溶液或悬浮液中分离出该化合物晶体，其中 * 代表该化合物为 (R) 或 (S) 异构体或其混合物，其他符号与上述相同。
• US6218427B1
  申请人：——

  公开号：US6218427B1

  公开（公告）日：2001-04-17
• US6479671B1
  申请人：——

  公开号：US6479671B1

  公开（公告）日：2002-11-12