4-Brom-2,3,5,6-tetramethyl-phenol | 17362-16-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-Brom-2,3,5,6-tetramethyl-phenol
• 英文别名: Bromdurenol；4-Bromo-2,3,5,6-tetramethylphenol
• CAS: 17362-16-2
• 化学式: C₁₀H₁₃BrO
• 分子量: 229.117
• InChiKey: IEDRBIMPVFYZOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-Brom-2,3,5,6-tetramethyl-phenol 在 甲醇 、 sodium tetrahydroborate 、 potassium phosphate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三丁基膦 、 potassium carbonate 、 potassium iodide 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 110.0h， 生成 methyl [(3S)-6-({4'-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)oxy]-2',3',5',6'-tetramethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate
  参考文献：
  名称：

  Optimization of (2,3-Dihydro-1-benzofuran-3-yl)acetic Acids: Discovery of a Non-Free Fatty Acid-Like, Highly Bioavailable G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonist as a Glucose-Dependent Insulinotropic Agent

  摘要：

  G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) is a free fatty acid (FFA) receptor that mediates FFA-amplified glucose-stimulated insulin secretion in pancreatic beta-cells. We previously identified (2,3-dihydro-1-benzofuran-3-yl)acetic acid derivative 2 as a candidate, but it had relatively high lipophilicity. Adding a polar functional group on 2 yielded several compounds with lower lipophilicity and little effect on caspase-3/7 activity at 30 mu M (a marker of toxicity in human HepG2 hepatocytes). Three optimized compounds showed promising pharmacokinetic profiles with good in vivo effects. Of these, compound 16 had the lowest lipophilicity. Metabolic analysis of 16 showed a long-acting PK profile due to high resistance to beta-oxidation. Oral administration of 16 significantly reduced plasma glucose excursion and increased insulin secretion during an OGTT in type 2 diabetic rats. Compound 16 (TAK-875) is being evaluated in human clinical trials for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm300170m
• 作为产物：
  描述：

  2,3,5-三甲基苯酚 在 palladium 10% on activated carbon 、 氢气 、 溴 、 四氯化钛 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 34.5h， 生成 4-Brom-2,3,5,6-tetramethyl-phenol
  参考文献：
  名称：

  Optimization of (2,3-Dihydro-1-benzofuran-3-yl)acetic Acids: Discovery of a Non-Free Fatty Acid-Like, Highly Bioavailable G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonist as a Glucose-Dependent Insulinotropic Agent

  摘要：

  G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) is a free fatty acid (FFA) receptor that mediates FFA-amplified glucose-stimulated insulin secretion in pancreatic beta-cells. We previously identified (2,3-dihydro-1-benzofuran-3-yl)acetic acid derivative 2 as a candidate, but it had relatively high lipophilicity. Adding a polar functional group on 2 yielded several compounds with lower lipophilicity and little effect on caspase-3/7 activity at 30 mu M (a marker of toxicity in human HepG2 hepatocytes). Three optimized compounds showed promising pharmacokinetic profiles with good in vivo effects. Of these, compound 16 had the lowest lipophilicity. Metabolic analysis of 16 showed a long-acting PK profile due to high resistance to beta-oxidation. Oral administration of 16 significantly reduced plasma glucose excursion and increased insulin secretion during an OGTT in type 2 diabetic rats. Compound 16 (TAK-875) is being evaluated in human clinical trials for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm300170m

文献信息

• Pentamethylphenyl (Ph*) and Related Derivatives as Useful Acyl Protecting Groups for Organic Synthesis: A Preliminary Study
  作者：Timothy J. Donohoe、Choon Boon Cheong、James R. Frost

  DOI：10.1055/s-0040-1707289

  日期：2020.11

  A study of acyl protecting groups derived from the Ph* motif is reported. While initial studies indicated that a variety of functional groups were not compatible with the Br2-mediated cleavage conditions required to release the Ph* group, strategies involving the use of different reagents or a modification of Ph* itself (Ph*OH) were investigated to solve this problem.

  报道了对衍生自 Ph* 基序的酰基保护基团的研究。虽然最初的研究表明各种官能团与释放 Ph* 基团所需的 Br2 介导的裂解条件不相容，但研究了涉及使用不同试剂或修饰 Ph* 本身 (Ph*OH) 的策略以解决这个问题。
• Syntheses of Sterically Hindered Pyridinium Phenoxides as Model Compounds in Nonlinear Optics
  作者：Vincent Diemer、Hélène Chaumeil、Albert Defoin、Alain Fort、Alex Boeglin、Christiane Carré

  DOI：10.1002/ejoc.200600030

  日期：2006.6

  increase in the twist angle between the two aromatic rings leads to an enhancement of the NLO properties. In order to confirm this feature experimentally, it was necessary to prepare a series of new hindered pyridinium phenoxides. Their efficient syntheses by Suzuki cross-coupling reactions are described herein.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

  具有 π 共轭系统的非中心对称分子，其中包括苯酚吡啶等推挽分子，由于其非线性光学 (NLO) 特性，是一类有前途的新型光电子材料。建模研究表明，两个芳环之间扭曲角的增加导致 NLO 性能的增强。为了通过实验证实这一特征，有必要制备一系列新的受阻吡啶酚盐。本文描述了它们通过 Suzuki 交叉偶联反应的有效合成。 (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
• Stereoselective photochemical ring-opening of cyclohexa-2,4-dienones
  作者：A. J. Waring、M. R. Morris、M. M. Islam

  DOI：10.1039/j39710003274

  日期：——

  The stereoselectivity of the photochemical ring-opening of 6-acetoxy-6-methylcyclohexa-2,4-dienones to derivatives of hepta-3,5-dienoic acid has been shown to be general, and the stereochemistry of the products has been studied by use of n.m.r. long-range coupling and solvent-shift data. Two representative 6-benzoyloxy-analogues behave in a similar manner.

  已证明6-乙酰氧基-6-甲基环己-2,4-二烯酮对七-3,5-二烯酸衍生物的光化学开环的立体选择性是一般的，并且已经通过以下方法研究了产物的立体化学：使用核磁共振远程耦合和溶剂转移数据。两个代表性的6-苯甲酰氧基类似物的行为相似。
• Physician Practice Patterns in the Treatment of Isolated Systolic Hypertension in a Primary Care Setting
  作者：Jeff Borenstein、Joanna L. Whyte、Enkhe Badamgarav、Delia Vogel、Stephen Deutsch、Scott Weingarten、Pablo Lapuerta

  DOI：10.1111/j.1524-6175.2001.01218.x

  日期：2002.3

  The authors evaluated the treatment of isolated systolic hypertension based on medical record review of charts between 1998 and 1999 in a multispecialty physician practice group. Two age‐stratified random samples of ambulatory medical records were examined (393 patients aged ≥65 years and 251 patients aged 50–64 years). The samples corresponded to the practices of 35 primary care physicians who were surveyed about their hypertension care. Isolated systolic hypertension was defined as systolic blood pressure ≥140 mm Hg and diastolic blood pressure <90 mm Hg. Results showed that isolated systolic hypertension represented 76% and 45% of uncontrolled blood pressure in the older and middle‐aged samples, respectively. Isolated systolic hypertension was often undiagnosed and untreated. Physicians reported treatment thresholds and goals that were significantly less aggressive for their patients ≥65 years of age. Physician awareness and treatment of isolated systolic hypertension have not yet caught up with consensus guidelines, and older patients may be affected most by this gap.

  作者通过审查 1998 年至 1999 年间一家多专科医师实践团体的病历，评估了孤立性收缩期高血压的治疗方法。研究者检查了两个按年龄分层的随机样本的门诊病历（393 名 ≥65 岁患者和 251 名 50-64 岁患者）。这些样本对应于 35 名初级保健医生的实践，这些医生接受了关于其高血压护理的调查。孤立性收缩期高血压被定义为收缩压 ≥140 mm Hg 且舒张压 <90 mm Hg。结果显示，在老年样本和中年样本中，孤立性收缩期高血压分别占未控制血压的 76% 和 45%。孤立性收缩期高血压通常未被诊断和治疗。医生报告称，他们对 ≥65 岁患者的治疗阈值和目标明显不那么积极。医生对孤立性收缩期高血压的认识和治疗尚未赶上共识指南，老年患者可能受到这一差距的最大影响。
• FUSED CYCLIC COMPOUNDS
  申请人：Yasuma Tsuneo

  公开号：US20100004312A1

  公开（公告）日：2010-01-07

  The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof. The compound or a salt thereof or a prodrug thereof has a GPR40 receptor function modulating action and is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明提供一种化合物，其表示为公式（I）：其中每个符号如描述中所定义，或其盐。该化合物或其盐或其前药具有GPR40受体功能调节作用，并可用作胰岛素分泌剂或用于预防或治疗糖尿病等药物。