methyl 4-O-tert-butyldimethylsilyl-3,5-dimethoxybenzoate | 383176-01-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 4-O-tert-butyldimethylsilyl-3,5-dimethoxybenzoate
• 英文别名: 3',5'-dimethoxy-4'-(tert-butyldimethylsiloxy)acetophenone；1-[4-[tert-butyl(dimethyl)silyl]oxy-3,5-dimethoxyphenyl]ethanone
• CAS: 383176-01-0
• 化学式: C₁₆H₂₆O₄Si
• 分子量: 310.466
• InChiKey: BYHPPQHBKZHBCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-O-tert-butyldimethylsilyl-3,5-dimethoxybenzoate 在 四丁基氟化铵 作用下， 以92%的产率得到乙酰丁香酮
  参考文献：
  名称：

  Inverse electron demand hetero-Diels–Alder reaction in preparing 1,4-benzodioxin from o-quinone and enamine

  摘要：

  A process for synthesizing 1,4-benzodioxin, through oxidation of a phenol to an o-quinone followed by treatment with an enamine, has been developed. Adduct stereochemistry is found to be retained via this one-pot reaction. The method uses hypervalent iodine reagent under mild conditions and is compatible with a wide scope of phenols and enamines. Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetlet.2013.09.013
• 作为产物：
  描述：

  丁香醛 在 咪唑 、 N-甲基吲哚酮 、 四丙基高钌酸铵 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 methyl 4-O-tert-butyldimethylsilyl-3,5-dimethoxybenzoate
  参考文献：
  名称：

  Total synthesis of (±)-nitidanin and novel procedures for determination of the location of the side chains on 1,4-benzodioxane

  摘要：

  Regioselective cycloaddition of o-quinone 4 and protected sinapyl alcohol 2 gave 1,4-benzodioxane 5, which was converted to (+/-)-nitidanin (6), an antimalarial compound. Two novel procedures were developed to determine the location of the side chains of the adduct (5) based on partial ring cleavage. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.11.170

文献信息

• 1, 3-bis-(substituted-phenyl)-2-propen-1-ones and their use to treat VCAM-1 mediated disorders
  申请人：Atherogenics, Inc.

  公开号：US06608101B1

  公开（公告）日：2003-08-19

  It has been discovered certain 1,3-bis-(substituted-phenyl)-2-propen-1-ones, including compounds of formula (I) inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorders that are mediated by VCAM-1 include, but are not limited to arthritis, asthma, dermatitis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease.

  已经发现了某些1,3-双(取代苯基)-2-丙烯-1-酮，包括式(I)化合物抑制VCAM-1的表达，因此可以用来治疗由VCAM-1介导的患者的疾病。由VCAM-1介导的炎症性疾病的例子包括但不限于关节炎、哮喘、皮炎、囊性纤维化、移植后晚期和慢性固体器官排斥反应、多发性硬化、系统性红斑狼疮、炎症性肠病、自身免疫糖尿病、糖尿病视网膜病变、鼻炎、缺血再灌注损伤、血管成形术后再狭窄、慢性阻塞性肺疾病（COPD）、肾小球肾炎、格雷夫斯病、胃肠道过敏、结膜炎、动脉粥样硬化、冠状动脉疾病、心绞痛和小动脉疾病。
• 1,3-bis-(substituted-phenyl)-2-propen-1-ones and their use to treat VCAM-1 mediated disorders
  申请人：Atherogenics Pharmaceuticals, Inc.

  公开号：US20030236298A1

  公开（公告）日：2003-12-25

  It has been discovered certain 1,3-bis-(substituted-phenyl)-2-propen-1-ones, including compounds of formula (I) inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorders that are mediated by VCAM-1 include, but are not limited to arthritis, asthma, dermatitis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease.

  已经发现了某些1,3-双-(取代苯基)-2-丙烯-1-酮，包括公式(I)化合物抑制VCAM-1的表达，因此可用于治疗受VCAM-1介导的疾病的患者。VCAM-1介导的炎症性疾病的例子包括但不限于关节炎、哮喘、皮炎、囊性纤维化、移植后晚期和慢性实体器官排斥、多发性硬化症、系统性红斑狼疮、炎症性肠病、自身免疫性糖尿病、糖尿病视网膜病变、鼻炎、缺血再灌注损伤、血管成形术后再狭窄、慢性阻塞性肺疾病（COPD）、肾小球肾炎、格雷夫斯病、胃肠道过敏、结膜炎、动脉粥样硬化、冠状动脉疾病、心绞痛和小动脉疾病。
• 1,3-Bis-(substituted-phenyl)-2-propen-1-ones and their use to treat VCAM-1 mediated disorders
  申请人：Meng Q. Charles

  公开号：US20060258735A1

  公开（公告）日：2006-11-16

  It has been discovered certain 1,3-bis-(substituted-phenyl)-2-propen-1-ones, including compounds of formula (I) inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorders that are mediated by VCAM-1 include, but are not limited to arthritis, asthma, dermatitis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease.

  已经发现某些1,3-双-(取代苯基)-2-丙烯-1-酮，包括公式（I）化合物抑制VCAM-1的表达，因此可以用于治疗由VCAM-1介导的患者疾病。由VCAM-1介导的炎症性疾病的例子包括但不限于关节炎，哮喘，皮炎，囊性纤维化，移植后晚期和慢性实体器官排斥，多发性硬化症，系统性红斑狼疮，炎症性肠病，自身免疫性糖尿病，糖尿病视网膜病变，鼻炎，缺血再灌注损伤，血管成形术后再狭窄，慢性阻塞性肺疾病（COPD），肾小球肾炎，Graves病，胃肠道过敏，结膜炎，动脉粥样硬化，冠状动脉疾病，心绞痛和小动脉疾病。
• Total synthesis of (±)-nitidanin and novel procedures for determination of the location of the side chains on 1,4-benzodioxane
  作者：Atsuhito Kuboki、Toru Yamamoto、Mamie Taira、Tetsuya Arishige、Susumu Ohira

  DOI：10.1016/j.tetlet.2006.11.170

  日期：2007.1

  Regioselective cycloaddition of o-quinone 4 and protected sinapyl alcohol 2 gave 1,4-benzodioxane 5, which was converted to (+/-)-nitidanin (6), an antimalarial compound. Two novel procedures were developed to determine the location of the side chains of the adduct (5) based on partial ring cleavage. (c) 2006 Elsevier Ltd. All rights reserved.
• An in silico-designed flavone derivative, 6-fluoro-4′-hydroxy-3′,5′-dimetoxyflavone, has a greater anti-human cytomegalovirus effect than ganciclovir in infected cells
  作者：Kazuhiro J. Fujimoto、Daiki Nema、Masayuki Ninomiya、Mamoru Koketsu、Hidetaka Sadanari、Masaya Takemoto、Tohru Daikoku、Tsugiya Murayama

  DOI：10.1016/j.antiviral.2018.03.006

  日期：2018.6

  A novel type of antiviral agent for human cytomegalovirus (HCMV) is required, because the appearance of ganciclovir (GCV) resistant viruses has been reported. Tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone) has been shown to suppress significantly HCMV replication in human embryonic lung (HEL) fibroblast cells. Recently, we revealed that the action of tricin is different from that of GCV and cyclin-dependent kinase 9 (CDK9) is one of the target proteins of tricin. These results suggested that tricin is considered as a novel type of anti-HCMV agent. However, its anti-HCMV potency is not greater than that of GCV. This study tried to develop novel compounds with much greater anti-HCMV activity than GCV. We first made modifications to tricin by introducing fluorine atom, and then performed molecular docking simulations using the designed compounds and CDK9. The calculated binding energies showed that 6F-tricin (6-fluoro-4'-hydroxy-3',5'-dimetoxyflavone) binds to CDK9 much stronger than tricin. Based on these results, 6F-tricin was synthesized, and then its anti-HCMV effect was analyzed in HEL cell cultures. As a result, 6F-tricin strongly suppressed HCMV replication in a dose-dependent manner. The anti-HCMV activity with a 50% effective concentration (EC50) was 0.126 nM, corresponding to about 1/200 and 1/400 of EC50 of GCV (27.5 nM) and tricin (54.3 nM), respectively. Moreover, 6F-tricin had no cytotoxicity against HEL cells at concentrations up to 10 mu M. We further performed detailed analysis on the amino acid contributions to the binding energies and found that the strong binding affinity for 6F-tricin to CDK9 is attributed to the specific binding orientation of 6F-tricin in the ATP-binding site. These results suggest that 6F-tricin is a promising candidate for anti-HCMV drug development.