5-isopropoxy-2-hydroxyacetophenone | 152810-05-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-isopropoxy-2-hydroxyacetophenone
• 英文别名: 1-(2-Hydroxy-5-propan-2-yloxyphenyl)ethanone
• CAS: 152810-05-4
• 化学式: C₁₁H₁₄O₃
• 分子量: 194.23
• InChiKey: WUBUMWDDBZWMMS-UHFFFAOYSA-N

物化性质

• 沸点：
  295.9±20.0 °C(Predicted)
• 密度：
  1.098±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  3
• 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：

  5-isopropoxy-2-hydroxyacetophenone 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 6-isopropoxy-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：

  2,5-二羟基苯乙酮 、 2-溴丙烷 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以51.3%的产率得到5-isopropoxy-2-hydroxyacetophenone
  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

• Chromene-3-carboxylate derivatives
  申请人：Shionogi & Co., Ltd.

  公开号：US06218427B1

  公开（公告）日：2001-04-17

  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.

  本发明提供了一种化合物，其化学式为（I）： 其中R1、R2、R3和R4分别独立地为氢、可选择取代的烷基、羟基、可选择取代的烷氧基或类似物，R5为可选择取代的烷基、可选择取代的芳基、可选择取代的杂环基或类似物，R6为氢、可选择取代的烷基或类似物，R7为氢、可选择取代的烷基、可选择取代的烷氧基、可选择取代的芳基、可选择取代的杂环基或类似物，A为S或O，虚线表示键的存在或缺失，以及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、外周循环不足改善剂或巨噬细胞泡沫细胞形成抑制剂的药物组合物或药物组合物。
• Palladium-Catalyzed Intramolecular Cross-Coupling of Unactivated C(sp³)–H and C(sp²)–H Bonds
  作者：Zhuo Wu、Zechen Wu、Xueliang Sun、Weixin Qi、Zhengyang Zhang、Yanghui Zhang

  DOI：10.1021/acs.orglett.1c02567

  日期：2021.9.17

  C–C bonds, and the cross-coupling of unactivated C(sp3)–H and C(sp2)–H bonds is challenging and remains to be investigated. We have developed the Pd-catalyzed intramolecular coupling of inert C(sp3)–H and C(sp2)–H bonds. The reaction proceeded by o-methyl oxime-directed aryl C(sp2)–H activation and subsequent alkyl C(sp3)–H cleavage, generating C(sp2),C(sp3)-palladacycles as the key intermediates. Dihydrobenzofurans

  直接 C-H/C-H 偶联是构建 C-C 键的一种有吸引力的方法，未活化的 C(sp 3 )-H 和 C(sp 2 )-H 键的交叉偶联具有挑战性，并且仍有待研究被调查。我们开发了 Pd 催化的惰性 C(sp 3 )-H 和 C(sp 2 )-H 键的分子内偶联。该反应通过邻甲基肟导向的芳基 C(sp 2 )-H 活化和随后的烷基 C(sp 3 )-H 裂解进行，生成 C(sp 2 ),C(sp 3 )-钯环作为关键中间体。最终产物形成二氢苯并呋喃和茚满。
• Effect of the Chromone Core Substitution of Dirchromone on the Resultant Biological Activities
  作者：Alexis St-Gelais、Jérôme Alsarraf、Jean Legault、Joanne Plourde、André Pichette

  DOI：10.1021/acs.jnatprod.1c00385

  日期：2021.11.26

  Dirchromone is a bioactive vinyl sulfoxide-bearing chromone first isolated from the shrub Dirca palustris. Altogether, 32 of its derivatives were prepared to assess the effect of substitution of its chromone core upon activities against cancer cell lines, Gram-positive bacteria, and fungi (such as Candida albicans). All compounds were synthesized following a synthetic strategy involving Pummerer and

  Dirchromone 是一种生物活性的带有乙烯基亚砜的色酮，首先从灌木Dirca palustris中分离出来。总共制备了 32 种衍生物来评估其色酮核心取代对癌细胞系、革兰氏阳性细菌和真菌（如白色念珠菌）活性的影响。）。所有化合物都是按照涉及 Pummerer 和软烯醇化 Baker-Venkataraman 重排的合成策略合成的。取代基位置的变化对测试的活性几乎没有影响。细胞毒性和抗菌作用之间没有相关性，表明不同的潜在作用机制。特别是羟基和氰化物取代基降低了细胞毒性，后者具有增强的抗菌活性。6-烷氧基二色酮的高级同系物也表现出逐渐出现的抗真菌活性。其他修饰对细胞毒性有中等影响，一些衍生物导致效力增加。这种行为突出了天然二色酮药效团对装饰的稳健性，从而为更精细的未来药物设计铺平了道路。
• Practical Enantioselective Synthesis of Endothelin Antagonist S-1255 by Dynamic Resolution of 4-Methoxychromene-3-carboxylic Acid Intermediate
  作者：Toshiro Konoike、Ken-ichi Matsumura、Tadahiko Yorifuji、Shoji Shinomoto、Yutaka Ide、Takashi Ohya

  DOI：10.1021/jo0261092

  日期：2002.11.1

  carbon-carbon bond formation between the C4 carbon and the p-anisyl group was accomplished by a conjugate addition-elimination reaction of Grignard reagent 3 to (R)-16 to give 1 having 98% ee. Owing to high efficiencies of functional group transformations, carbon-carbon bond formations, and the dynamic resolution, the synthesis required no chromatographic purification and was amenable to a multikilogram-scale preparation

  描述了对映体纯的S-1255（1）（一种有效的口服活性ET（A）受体拮抗剂）的实用多千克级合成方法。利用容易获得的原料和试剂，从2,5-二羟基苯乙酮8开始的整个反应序列在温和的条件下进行，以优异的化学收率（8步，总收率41％）和高对映体纯度（98％）得到1 ee）。合成的关键步骤是关键中间体16的动态拆分。从外消旋体16以结晶形式（1S，2R）获得具有97-99％ee的（R）-甲氧基酸（R）-16，产率为83-84％。 ）-（+）-去氧麻黄碱或（+）-辛可宁盐的动态拆分包括同时结晶和原位外消旋。讨论了通过开环的两性离子中间体进行动态拆分的机理。在最后的合成步骤中，通过格氏试剂3与（R）-16的共轭加成-消除反应，在C4碳和对-茴香基之间有效地形成碳-碳键，得到具有98％ee的1。由于高效的官能团转化，碳-碳键形成和动态拆分，该合成方法无需进行色谱纯化，可进行多千克级的制备。通过此过程成功制
• 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。