3-hydroxy-3,3-diphenyl-2,2-dimethylpropanoic acid | 27925-29-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-hydroxy-3,3-diphenyl-2,2-dimethylpropanoic acid
• 英文别名: α-<α-Hydroxy-benzhydryl>-isobuttersaeure；3-Hydroxy-2,2-dimethyl-3,3-diphenylpropanoic acid
• CAS: 27925-29-7
• 化学式: C₁₇H₁₈O₃
• 分子量: 270.328
• InChiKey: PCLPKHJVFQXOOT-UHFFFAOYSA-N

物化性质

• 熔点：
  162 °C
• 沸点：
  427.4±33.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydroxy-3,3-diphenyl-2,2-dimethylpropanoic acid 在 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 以46%的产率得到
  参考文献：
  名称：

  阳极氧化通过电化学调节引发β-羟基羧酸的不同1,2-和1,4-基转移反应

  摘要：

  我们报告了一套由电化学调节的协议，用于从相同的β-羟基羧酸原料中合成酮和β-酮​​酸酯。通过电化学控制，羧酸的阳极氧化以单电子或双电子方式进行，从而导致1,4-芳基转移或半频哪醇型1,2-基团转移产物具有出色的化学选择性。1,4-芳基转移代表了碳-氧基转移通过根本机制。与先前报道的自由基基团转移反应相反，此1,4-基团转移过程的特征在于富电子芳基取代基的迁移。此外，利用这些化学选择性电化学氧化方案，可以以优异的产率合成多种酮和β-酮​​酯，包括具有难以接近的中等尺寸环的酮和β-酮​​酯。

  DOI：

  10.1039/d0sc02386h
• 作为产物：
  描述：

  在 盐酸 作用下， 以 苯 为溶剂， 生成 3-hydroxy-3,3-diphenyl-2,2-dimethylpropanoic acid
  参考文献：
  名称：

  Bogavac, M.; Arsenijevic, L.; Arsenijevic, V., Bulletin de la Societe Chimique de France, 1980, vol. 2, # 3-4, p. 145 - 147

  摘要：

  DOI：

文献信息

• Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids
  作者：Jelena S. Savić、Sanda P. Dilber、Bojan D. Marković、Marina T. Milenković、Sote M. Vladimirov、Ivan O. Juranić

  DOI：10.3390/molecules16086645

  日期：——

  Six β-hydroxy-β-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the β-hydroxy-β-aryl propanoic acids, and to elucidate the effect α-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carragenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED50 values is between 127 µmol/kg and 15 µmol/kg, while the result for ibuprofen is 51.7 µmol/kg. Only slight hyperaemia or few petechiae were spotted on rat’s stomach. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenyl-propanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions.

  我们采用一种改良的 Reformatsky 反应合成了六种 β-羟基-β-芳基丙酸。这些酸属于芳基丙酸类化合物，在结构上与布洛芬等非甾体抗炎药相似，因此具有抗炎活性。这项工作的目的是测定抗炎活性，检查胃耐受性，并进行分子对接实验，以在β-羟基-β-芳基丙酸中找出潜在的 COX-2 抑制剂，并阐明α-甲基取代对抗炎活性的影响。采用卡拉根南诱导爪水肿法测定了大鼠的抗炎活性和胃耐受性，并使用 Autodock v4.0.1 进行了对接研究。ED50 值范围介于 127 µmol/kg 和 15 µmol/kg 之间，而布洛芬的 ED50 值为 51.7 µmol/kg。大鼠的胃部仅出现轻微的高血症或少量瘀斑。结果表明，所有化合物在口服后都具有显著的抗炎活性，其中 2-甲基-3-羟基-3,3-二苯基丙酸的活性最强，超过了标准的非甾体抗炎药布洛芬。另一种化合物--3-羟基-3,3-二苯基丙酸的活性与布洛芬相当，而且无手性，经证实无毒。大多数研究化合物都与 P3 锚点有相互作用，就像 COX-2 选择性抑制剂一样。没有任何受测物质或布洛芬会产生明显的胃部病变。
• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
  申请人：Yang Bingwei Vera

  公开号：US20100063051A1

  公开（公告）日：2010-03-11

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I) an enantiomer, diastereomer, tautomer, solvate (e.g. a hydrate), or a pharmaceutically-acceptable salt, thereof, wherein: M is selected from alkyl, substituted alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl, provided that if M is alkyl then R 6 and R 7 taken together with the carbon atom to which they are both attached are selected from a group other than cycloalkyl; Q is selected from (i) hydrogen, C 1 -C 4 alkyl, and substituted C 1 -C 4 alkyl; or (ii) Q and R 6 are combined with the carbon atoms to which they are attached to form a 3- to 6-membered cycloalkyl; or (iii) Q and M a M are combined with the carbon atom(s) to which they are attached to form a 3- to 7-membered ring containing 1-2 heteroatoms which are independently selected from the group consisting of O, S, SO 2 , and N which ring may be optionally substituted with 0-2 R 5 groups or carbonyl; Z is selected from cycloalkyl, heterocyclo, aryl, or heteroaryl; and M a , Z a , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , and R 22 are as defined herein. Also provided are pharmaceutical compositions and methods of treating metabolic and inflammatory- or immune-associated diseases or disorders using said compounds.

  提供了一些新型非类固醇化合物，其在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病中非常有用，包括炎症和免疫性疾病、肥胖症和糖尿病，具有以下结构公式（I）的对映体、顺反异构体、互变异构体、溶剂化物（例如水合物）或其医药上可接受的盐，其中：M选自烷基、取代烷基、环烷基、芳基、杂环烷基和杂芳基，但如果M是烷基，则R6和R7与它们都连接的碳原子一起选自环烷基之外的一组；Q选自（i）氢、C1-C4烷基和取代的C1-C4烷基；或（ii）Q和R6与它们连接的碳原子结合形成3-到6-成员的环烷基；或（iii）Q和MaM与它们连接的碳原子结合形成1-2个杂原子（独立于O、S、SO2和N组成）的3-到7-成员的环，该环可以选择性地用0-2个R5基团或羰基取代；Z选自环烷基、杂环烷基、芳基或杂芳基；而Ma、Za、R1、R2、R3、R4、R6、R7和R22如本文所定义。还提供了制药组合物和使用所述化合物治疗代谢和炎症或免疫相关疾病或紊乱的方法。
• Angelo,B., Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques, 1970, vol. 270, p. 1471 - 1473
  作者：Angelo,B.

  DOI：——

  日期：——
• Stereospecific introduction of double bounds via thermolysis of .beta.-lactones
  作者：Waldemar Adam、Jaime Baeza、Ju-Chao Liu

  DOI：10.1021/ja00761a036

  日期：1972.3
• Synthesis of .beta.-hydroxy acids using .alpha.-lithiated carboxylic acid salts
  作者：G. W. Moersch、A. R. Burkett

  DOI：10.1021/jo00807a030

  日期：1971.4