1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-fluoroindole | 903550-98-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-fluoroindole
• 英文别名: (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-fluoro-1H-indol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate；4-fluoro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole；4-Fluoro-1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)indole；[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(4-fluoroindol-1-yl)oxan-2-yl]methyl acetate
• CAS: 903550-98-1
• 化学式: C₂₂H₂₄FNO₉
• 分子量: 465.432
• InChiKey: ZYSYLSUPRRNMSK-QMCAAQAGSA-N

物化性质

• 熔点：
  137-139 °C
• 沸点：
  552.8±50.0 °C(predicted)
• 密度：
  1.39±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-fluoroindole 在 甲醇 、 三乙基硅烷 、 aluminum (III) chloride 、 sodium tetrahydroborate 、 三氟化硼乙醚 、 chromium(III) chloride hexahydrate 、 sodium methylate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 3-(4-cyclopentylphenylmethyl)-4-fluoro-1-(β-D-glucopyranosyl)indole
  参考文献：
  名称：

  Novel Indole-N-glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor for Treatment of Type 2 Diabetes

  摘要：

  Inhibition of the renal sodium glucose cotransporter (SGLT) increases urinary glucose excretion (UGE) and thus reduces blood glucose levels during hyperglycemia. To explore the potential of new antihyperglycemic agents, we synthesized and determined the human SGLT2 (hSGLT2) inhibitory potential of novel substituted 3-benzylindole-N-glucosides 6. Optimization of 6 resulted in the discovery of 3-(4-cyclopropylbenzyl)-4-fluoroindole-N-glucoside 6a-4 (TA-1887), a highly potent and selective hSGLT2 inhibitor, with pronounced antihyperglycemic effects in high-fat diet-fed KK (HF-KK) mice. Our results suggest the potential of indole-N-glucosides as novel antihyperglycemic agents through inhibition of renal SGLT2.

  DOI：

  10.1021/ml400339b
• 作为产物：
  描述：

  4-氟-2,3-二氢-1H-吲哚盐酸盐 在 吡啶 、 4-二甲氨基吡啶 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 、 乙醇 、 氯仿 、 水 为溶剂， 反应 206.0h， 生成 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-fluoroindole
  参考文献：
  名称：

  Novel Indole-N-glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor for Treatment of Type 2 Diabetes

  摘要：

  Inhibition of the renal sodium glucose cotransporter (SGLT) increases urinary glucose excretion (UGE) and thus reduces blood glucose levels during hyperglycemia. To explore the potential of new antihyperglycemic agents, we synthesized and determined the human SGLT2 (hSGLT2) inhibitory potential of novel substituted 3-benzylindole-N-glucosides 6. Optimization of 6 resulted in the discovery of 3-(4-cyclopropylbenzyl)-4-fluoroindole-N-glucoside 6a-4 (TA-1887), a highly potent and selective hSGLT2 inhibitor, with pronounced antihyperglycemic effects in high-fat diet-fed KK (HF-KK) mice. Our results suggest the potential of indole-N-glucosides as novel antihyperglycemic agents through inhibition of renal SGLT2.

  DOI：

  10.1021/ml400339b

文献信息

• An Efficient Synthesis of 3-Substituted <i>N</i>-Glycoside Indoles Useful as Sodium-Dependent Glucose Transporter Inhibitors
  作者：Xun Li、Kenneth M. Wells、Shawn Branum、Sandra Damon、Scott Youells、Derek A. Beauchamp、David Palmer、Stephen Stefanick、Ronald K. Russell、William Murray

  DOI：10.1021/op3001355

  日期：2012.11.16

  A practical synthesis of two N-glycoside indoles 1 and 2, identified as highly potent sodium-dependent glucose transporter (SGLT) inhibitors is described. Highlights of the synthetic process include a selective and quantitative Vilsmeier acylation and a high-yielding Grignard coupling reaction. The chemistry developed has been applied to prepare two separate SGLT inhibitors 1 and 2 for clinical evaluation

  描述了两种N-糖苷吲哚1和2的实用合成方法，已确定它们是高效的钠依赖性葡萄糖转运蛋白（SGLT）抑制剂。合成过程的重点包括选择性和定量的Vilsmeier酰化反应和高产率的Grignard偶联反应。已开发的化学方法已用于制备两种单独的SGLT抑制剂1和2，无需进行色谱分析即可用于临床评估。
• Indole derivatives
  申请人：Nomura Sumihiro

  公开号：US20080027122A1

  公开（公告）日：2008-01-31

  Novel indole derivatives of formula (I) or a pharmaceutically acceptable salt thereof: wherein R 1 is fluorine, or chlorine, and R 2 is hydrogen, or fluorine, which are SGLT inhibitors and are useful for treatment or prevention of diabetes and related conditions.

  式(I)的新型吲哚衍生物或其药用盐：其中R1为氟或氯，R2为氢或氟，是SGLT抑制剂，可用于治疗或预防糖尿病及相关疾病。
• INDOLE DERIVATIVES
  申请人：NOMURA Sumihiro

  公开号：US20090258921A1

  公开（公告）日：2009-10-15

  Novel indole derivatives of formula (I) or a pharmaceutically acceptable salt thereof: wherein R 1 is halogen, or alkyl, R 2 is hydrogen, or halogen, Ar is phenyl, or thienyl, which may be substituted with halogen, alkyl, alkoxy, alkylthio, etc.

  式(I)的新型吲哚衍生物或其药学上可接受的盐：其中R1为卤素或烷基，R2为氢或卤素，Ar为苯基或噻吩基，可以被卤素、烷基、烷氧基、烷硫基等取代。
• Indole Derivatives
  申请人：Nomura Sumihiro

  公开号：US20080119422A1

  公开（公告）日：2008-05-22

  Novel indole derivatives of formula (I) or a pharmaceutically acceptable salt thereof: wherein R 1 is halogen, or alkyl, R 2 is hydrogen, or halogen, Ar is phenyl, or thienyl, which may be substituted with halogen, alkyl, alkoxy, alkylthio, etc.

  化合物的式子 (I) 或其药学上可接受的盐：其中 R1 是卤素或烷基，R2 是氢或卤素，Ar 是苯基或噻吩基，可以被卤素、烷基、烷氧基、烷硫基等取代。
• PROCESS FOR THE PREPARATION OF COMPOUNDS USEFUL AS INHIBITORS OF SGLT-2
  申请人：Wells Kenneth M.

  公开号：US20140206858A1

  公开（公告）日：2014-07-24

  The present invention is directed to a novel process for the preparation of compounds having inhibitory activity against sodium-dependent glucose transporter (SGLT) being present in the intestine or kidney.

  本发明涉及一种新型的制备具有抑制肠道或肾脏中存在的钠依赖性葡萄糖转运体（SGLT）活性的化合物的方法。