4-(4-methoxyphenyl)-3-methyl-4-oxobutyric acid | 5717-17-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-methoxyphenyl)-3-methyl-4-oxobutyric acid
• 英文别名: 4-(4-methoxyphenyl)-3-methyl-4-oxobutanoic acid；3-(4'-methoxybenzoyl)-3-methylpropionic acid；3-(4-Methoxybenzoyl)-butanoic acid；4-(4-Methoxy-phenyl)-3-methyl-4-oxo-buttersaeure
• CAS: 5717-17-9
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: HLIAREKHQFODGA-UHFFFAOYSA-N

物化性质

• 熔点：
  69-70 °C
• 沸点：
  418.9±25.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  4-(4-methoxyphenyl)-3-methyl-4-oxobutyric acid 在 三氯化铝 、 potassium carbonate 、 一水合肼 、 potassium iodide 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 cis-4-(3-chloro-4-methoxyphenyl)-2-{4-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenoxy]butyl}-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of cis-Tetrahydrophthalazinone/Pyridazinone Hybrids:  A Novel Series of Potent Dual PDE3/PDE4 Inhibitory Agents

  摘要：

  In this study, the synthesis and in vitro and in vivo pharmacological investigations of a new series of phthalazinone/pyridazinone hybrids with both PDE3 and PDE4 inhibitory activities are described. These compounds combine the pharmacophores of recently discovered 4a,5,8,8a-tetrahydro-2H-phthalazin-1-one-type inhibitors of PDE4 and the well-known 2H-pyridazin-3-one-type PDE3 inhibitors such as the tetrahydrobenzimidazoles. Most of the synthesized compounds are pharmacologically spoken PDE3/PDE4 hybrids. All hybrids show potent PDE4 inhibitory activity (pIC(50) = 7.0-8.7), whereas the pIC(50) values for inhibition of PDE3 vary from 5.4 to 7.5. In general, analogues with a 5-methyl-4,5-dihydropyridazinone moiety exhibit the highest PDE3 inhibitory activities. The highest in vivo antiinflammatory activity is displayed by phthalazinones 43 and 44 showing, at a dose of 30 mumol/kg po, 46% inhibition of arachidonic acid (AA) induced mouse ear edema. No correlation was found between the in vitro PDE3 and/or PDE4 inhibitory activity and the in vivo antiinflammatory capacity after oral dosing.

  DOI：

  10.1021/jm030776l
• 作为产物：
  描述：

  2-溴-1-(4-甲氧苯基)丙酮 在 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 4-(4-methoxyphenyl)-3-methyl-4-oxobutyric acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of cis-Tetrahydrophthalazinone/Pyridazinone Hybrids:  A Novel Series of Potent Dual PDE3/PDE4 Inhibitory Agents

  摘要：

  In this study, the synthesis and in vitro and in vivo pharmacological investigations of a new series of phthalazinone/pyridazinone hybrids with both PDE3 and PDE4 inhibitory activities are described. These compounds combine the pharmacophores of recently discovered 4a,5,8,8a-tetrahydro-2H-phthalazin-1-one-type inhibitors of PDE4 and the well-known 2H-pyridazin-3-one-type PDE3 inhibitors such as the tetrahydrobenzimidazoles. Most of the synthesized compounds are pharmacologically spoken PDE3/PDE4 hybrids. All hybrids show potent PDE4 inhibitory activity (pIC(50) = 7.0-8.7), whereas the pIC(50) values for inhibition of PDE3 vary from 5.4 to 7.5. In general, analogues with a 5-methyl-4,5-dihydropyridazinone moiety exhibit the highest PDE3 inhibitory activities. The highest in vivo antiinflammatory activity is displayed by phthalazinones 43 and 44 showing, at a dose of 30 mumol/kg po, 46% inhibition of arachidonic acid (AA) induced mouse ear edema. No correlation was found between the in vitro PDE3 and/or PDE4 inhibitory activity and the in vivo antiinflammatory capacity after oral dosing.

  DOI：

  10.1021/jm030776l

文献信息

• Catalytic Redox Chain Ring Opening of Lactones with Quinones To Synthesize Quinone-Containing Carboxylic Acids
  作者：Xiao-Long Xu、Zhi Li

  DOI：10.1021/acs.orglett.9b01672

  日期：2019.7.5

  Catalytic ring opening of five- to eight-membered lactones with quinones is achieved through a redox chain mechanism. With low loading of a simple metal triflate Lewis acid catalyst and a chain initiator, C–H bonds of many quinones were efficiently functionalized with carboxylic acid-containing side chains. This method also features 100% atom economy and wide substrate scope. A novel route to the anti-asthma

  五至八元内酯与醌的催化开环是通过氧化还原链机理实现的。在简单的三氟甲磺酸金属路易斯酸催化剂和链引发剂的低负载下，许多醌的C–H键被含羧酸的侧链有效地官能化。该方法还具有100％的原子经济性和广泛的底物范围。开发了一种抗哮喘药Seratrodast的新途径。机理研究表明，氧化还原链反应可能发生碳正离子中间体。
• PYRAZOLONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP2168960A1

  公开（公告）日：2010-03-31

  It is to provide a novel pyrazolone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1,R2: C1-6 alkyl; R3,R4: H, X, C1-6 alkoxy; Z:O, S; A:AA, BB, wherein AA represents wherein BB represents wherein R5: H, C1-6 alkyl ; R6,R7: C1-6 alkyl.

  提供一种新颖的吡唑酮衍生物， represented by the following general formula (1)，该衍生物可用作药物，并具有磷酸二酯酶抑制作用： 其中 R1，R2：C1-6烷基；R3，R4：H，X，C1-6烷氧基；Z：O，S；A：AA，BB，其中AA代表 其中BB代表 其中R5：H，C1-6烷基；R6，R7：C1-6烷基。
• PYRIDAZINONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP2168959A1

  公开（公告）日：2010-03-31

  It is to provide a novel pyridazinone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1 represents H or C1-6 alkyl, each of R2 and R3 represents H, X, C1-6 alkoxy, Z represents O or S, and A represents AA or BB, wherein AA represents: and BB represents: wherein R4 represents H or C1-6 alkyl, and each of R5 and R6 represents C1-6 alkyl.

  提供一种新颖的吡啶并酮衍生物，其通式如下（1），可用作药物，并具有磷酸二酯酶抑制作用： 其中R1代表H或C1-6烷基，R2和R3各自代表H、X、C1-6烷氧基，Z代表O或S，A代表AA或BB，其中AA代表： 而BB代表： 其中R4代表H或C1-6烷基，R5和R6各自代表C1-6烷基。
• Bio-based crotonic acid from polyhydroxybutyrate: synthesis and photocatalyzed hydroacylation
  作者：Adriano Parodi、Alexandra Jorea、Maurizio Fagnoni、Davide Ravelli、Chiara Samorì、Cristian Torri、Paola Galletti

  DOI：10.1039/d1gc00421b

  日期：——

  through a photochemical approach. The photocatalytic addition (promoted by tetrabutylammonium decatungstate – TBADT) of aliphatic and aromatic aldehydes to crotonic acid took place under solar-simulated light irradiation. TBADT triggered the in situ formation of valuable acyl radicals from the corresponding aldehydes, thus inducing the desired hydroacylation via radical conjugate addition. Notably,

  开发了一种新颖的热解蒸馏工艺以解聚聚羟基丁酸酯（PHB），以选择性生产巴豆酸。将所采用的条件（170°C，150 mbar）应用于纯净的PHB和富含PHB的细菌，其中含有60％和30％的PHB，巴豆酸的回收率分别为92％，78％和58％。所开发方法的高效率为直接生产生物基巴豆酸奠定了基础，巴豆酸作为一种平台化学品已通过光化学方法进行了研究。在阳光模拟的光照射下，将脂肪族和芳香族醛类的光催化加成反应（由四丁基癸二酸铵-TBADT促进）。TBADT触发了原位由相应的醛形成有价值的酰基自由基，从而通过自由基共轭加成反应诱导所需的加氢酰化反应。值得注意的是，官能化以令人满意的产率完全独立于所采用的巴豆酸样品（无论是商业的还是基于生物的）而进行。
• Foodstuffs containing sweetness inhibiting agents and process for inhibiting the sweetness perception of a foodstuff
  申请人：GENERAL FOODS CORPORATION

  公开号：EP0156317A2

  公开（公告）日：1985-10-02

  @ Foodstuffs containing sweetness inhibitors having the general formula: wherein R7 is selected from the group consisting of hydrogen and C1-C3 alkyl, R. is selected from the group consisting of hydrogen and C1-C3 alkyl and wherein R9 is the group wherein R2, R3, R4, R. and R4 are independently selected from the group consisting of hydrogen, C1-C3 alkyl, C1-C3 alkoxy, C1-C2 hydroxyalkyl, hydroxy and COOH; and the non-toxic salts thereof. Disclosed is also a process for inhibiting the sweetness perception of a foodstuff.

  其中R7选自由氢和C1-C3烷基组成的组，R.选自由氢和C1-C3烷基组成的组，R9是R2、R3、R4、R.和R4独立地选自由氢、C1-C3烷基、C1-C3烷氧基、C1-C2羟烷基、羟基和COOH组成的组，以及它们的无毒盐。 还公开了一种抑制食品甜味感知的工艺。