(2R)-(2,4/3,5)-2,3,4-tribenzyloxy-5-(benzyloxymethyl)cyclohexanone | 124330-57-0

• 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: (2R)-(2,4/3,5)-2,3,4-tribenzyloxy-5-(benzyloxymethyl)cyclohexanone
• 英文别名: tetrabenzylvalidone；(2R,3S,4R,5R)-2,3,4-tris(benzyloxy)-5-[(benzyloxy)methyl]cyclohexanone；(2R,3S,4R,5R)-2,4,5-trisbenzyloxy-5-(benzyloxymethyl)-cyclohexanone；(2R,3S,4R,5R)-2,3,4-tris(phenylmethoxy)-5-(phenylmethoxymethyl)cyclohexan-1-one
• CAS: 124330-57-0
• 化学式: C₃₅H₃₆O₅
• 分子量: 536.668
• InChiKey: SUNQRZNLNFNHJL-FVIDNIPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R)-(2,4/3,5)-2,3,4-tribenzyloxy-5-(benzyloxymethyl)cyclohexanone 在 正丁基锂 、 20 % Pd(OH)2/C 、 氢气 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.17h， 生成 4-{3-[(3aS,4S,5aR,9aR,9bR)-2,2,8,8-tetramethylhexahydro[1,3]dioxolo[4',5':3,4]benzo[1,2-d][1,3]dioxin-4-yl]benzyl}phenol
  参考文献：
  名称：

  C-Aryl 5a-carba-β-d-glucopyranosides as novel sodium glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes

  摘要：

  C-Aryl 5a-carba-beta-D-glucopyranose derivatives were synthesized and evaluated for inhibition activity against hSGLT1 and hSGLT2. Modifications to the substituents on the two benzene rings resulted in enhanced hSGLT2 inhibition activity and extremely high hSGLT2 selectivity versus SGLT1. Using the created superimposed model, the reason for the high hSGLT2 selectivity was speculated to be that additional substituents occupied a new space, in a different way than known inhibitors. Among the tested compounds, the ethoxy compound 5h with high hSGLT2 selectivity exhibited more potent and longer hypoglycemic action in db/db mice than our O-carbasugar compound (1) and sergliflozin (2), which could be explained by its improved PK profiles relative to those of the two compounds. These results indicated that 5h might be a promising drug candidate for the treatment of type 2 diabetes. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.053
• 作为产物：
  描述：

  carbocyclic 2,3,4,6-tetra-O-benzyl-α-D-glucopyranose 在 4 A molecular sieve 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (2R)-(2,4/3,5)-2,3,4-tribenzyloxy-5-(benzyloxymethyl)cyclohexanone
  参考文献：
  名称：

  Tsunoda, Hidetoshi; Ogawa, Seiichiro, Liebigs Annalen, 1995, # 2, p. 267 - 278

  摘要：

  DOI：

文献信息

• Synthesis and Evaluation as Glycosidase Inhibitors of Carbasugar-Derived Spirodiaziridines, Spirodiazirines, and Spiroaziridines
  作者：Peter Kapferer、Véronique Birault、Jean-François Poisson、Andrea Vasella

  DOI：10.1002/hlca.200390178

  日期：2003.6

  irreversible inhibitor of the β-glucosidase from Caldocellum saccharolyticum and a weak reversible inhibitor of the α-glucosidase from yeast, but did not inhibit the β-glucosidases from almonds. The poorly stable aziridine 21 weakly inhibited the three enzymes. Similarly, 1-epivalidamine (pKHA=8.4) proved only a weak inhibitor. The known cyclopentylamine 34 (pKHA=7.9), however, is a micromolar inhibitor of these

  从有效氧胺A衍生的环己酮5制备了潜在的α-和β-葡萄糖苷酶抑制剂spirodiaziridines 6和9。5的三甲基甲硅烷基保护基对于以高收率形成6至关重要。氧化6得到7。所述diaziridine 6（对ķ HA = 2.6）和二吖丙因7不抑制β从杏仁葡糖苷酶，所述β从葡萄糖苷酶Caldocellum糖热厌氧杆菌，和α-酵母中的葡萄糖苷酶。N-苄基二氮丙啶9是α-葡萄糖苷酶的非常弱的抑制剂，但不抑制β-葡萄糖苷酶。为了观察弱抑制是由于二氮丙啶的碱度低还是由于几何因素所致，我们制备了螺氮丙啶21和25以及1-epivalidamine（32）。将已知的环己酮10甲基化并环氧化为16和17。16和17的叠氮基打开，甲磺酰化，LiAlH 4还原和脱保护得到氮丙啶21和25。1-Epivalidamine（32）由已知的氨基葡萄糖29制备。氮丙啶25（p K HA = 6.8）是来自糖化卡尔德
• Electrochemical Evaluation of Interaction between Avidin and Biotin Self-assembled Using Marker Ions
  作者：Hideki Kuramitz、Kazuharu Sugawara、Hiroshi Nakamura、Shunitz Tanaka

  DOI：10.1246/cl.1999.725

  日期：1999.8

  The interaction between avidin and biotin as self-assembled monolayer on a gold electrode surface was electrochemically evaluated by monitoring the changes in the electrode response of the ferrocyanide ion as redox-marker. It was clarified that the permeability changes of avidin membrane introduced onto the biotin self-assembled monolayer against ferrocyanide ion were ascribed to electrostatic interaction between avidin and marker ion.

  亲和素与生物素在金电极表面形成自组装单分子层的相互作用通过监测铁氰化物离子的电极响应变化进行了电化学评估。研究表明，引入到生物素自组装单分子层上的亲和素膜对铁氰化物离子的渗透性变化是由于亲和素与标记离子之间的静电相互作用所致。
• Novel Cyclohexane Derivative, Prodrug Thereof and Salt Thereof, and Therapeutic Agent Containing the Same for Diabetes
  申请人：Matsuoka Hiroharu

  公开号：US20080318874A1

  公开（公告）日：2008-12-25

  A cyclohexane derivative having the function of reducing a blood sugar level and having preferable properties required of medicines, such as long-lasting drug activity, metabolic stability, and safety; and a medicinal composition for use in the prevention or treatment of diseases attributable to hyperglycemia, such as diabetes, e.g., insulin dependent diabetes mellitus (type 1 diabetes) or noninsulin-dependent diabetes mellitus (type 2 diabetes), complications of diabetes, and obesity. The derivative is a compound represented by the formula (I): (wherein A is —O—, —CH 2 —, or —NH—; n is an integer selected between 0 and 1; R 6 and R 7 each independently is hydrogen or C 1-6 alkyl; m is an integer selected among 1-3; Q is selected among the following formulae Q 1 to Q 5 ; Ar 1 is optionally substituted arylene or optionally substituted heteroarylene, provided that the heteroarylene may be bonded to an aromatic carbocycle or aromatic heterocycle to form a fused ring; and Ar 2 is optionally substituted aryl or optionally substituted heteroaryl), a prodrug of the compound, or a pharmaceutically acceptable salt of either. Also provided are a medicine, a medicinal composition, or the like each containing the compound.

  一种环己烷衍生物，具有降低血糖水平的功能，并具有药物所需的优良特性，如持久的药物活性、代谢稳定性和安全性；以及用于预防或治疗与高血糖相关的疾病，如糖尿病，例如胰岛素依赖性糖尿病（1型糖尿病）或非胰岛素依赖性糖尿病（2型糖尿病），糖尿病并发症和肥胖症的药物组合物。该衍生物是由式（I）表示的化合物：（其中A是-O-、-CH2-或-NH-；n是在0和1之间选择的整数；R6和R7各自独立地是氢或C1-6烷基；m是在1-3之间选择的整数；Q在以下式Q1至Q5之间选择；Ar1是可选的取代芳基或可选的取代杂环芳基，但杂环芳基可以与芳香环或芳香杂环结合形成融合环；Ar2是可选的取代芳基或可选的取代杂环芳基），该化合物的前药物或任一药物学上可接受的盐。还提供了含有该化合物的药物、药物组合物等。
• NOVEL CYCLOHEXANE DERIVATIVE, PRODRUG THEREOF AND SALT THEREOF, AND THERAPEUTIC AGENT CONTAINING THE SAME FOR DIABETES
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1783110A1

  公开（公告）日：2007-05-09

  A cyclohexane derivative having the function of reducing a blood sugar level and having preferable properties required of medicines, such as long-lasting drug activity, metabolic stability, and safety; and a medicinal composition for use in the prevention or treatment of diseases attributable to hyperglycemia, such as diabetes, e.g., insulin dependent diabetes mellitus (type 1 diabetes) or noninsulin-dependent diabetes mellitus (type 2 diabetes), complications of diabetes, and obesity. The derivative is a compound represented by the formula (I): (wherein A is -O-, -CH2-, or -NH-; n is an integer selected between 0 and 1; R6 and R7 each independently is hydrogen or C1-6 alkyl; m is an integer selected among 1-3; Q is selected among the following formulae Q1 to Q5; Ar1 is optionally substituted arylene or optionally substituted heteroarylene, provided that the heteroarylene may be bonded to an aromatic carbocycle or aromatic heterocycle to form a fused ring; and Ar2 is optionally substituted aryl or optionally substituted heteroaryl), a prodrug of the compound, or a pharmaceutically acceptable salt of either. Also provided are a medicine, a medicinal composition, or the like each containing the compound.

  一种环己烷衍生物，具有降低血糖水平的功能，并具有药物所需的优越性能，如持久的药物活性、代谢稳定性和安全性；以及一种药物组合物，用于预防或治疗由高血糖引起的疾病，如糖尿病，如胰岛素依赖型糖尿病（1型糖尿病）或非胰岛素依赖型糖尿病（2型糖尿病）、糖尿病并发症和肥胖症。衍生物是由式（I）代表的化合物： (其中 A 是-O-、-CH2-或-NH-；n 是选自 0 和 1 之间的整数；R6 和 R7 各自独立地是氢或 C1-6 烷基；m 是选自 1-3 之间的整数；Q 是选自下式 Q1 至 Q5 之间的整数； Ar1是任选取代的芳基或任选取代的杂芳基，条件是杂芳基可以键合到芳香族碳环或芳香族杂环上以形成融合环；以及Ar2是任选取代的芳基或任选取代的杂芳基）、该化合物的原药或二者的药学上可接受的盐。还提供了含有该化合物的药物、药物组合物或类似物。
• EP1783110
  申请人：——

  公开号：——

  公开（公告）日：——