达格列净杂质14 | 2271248-78-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 达格列净杂质14
• 英文名称: (3R,4R,5R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-5-((R)-1,2-dihydroxyethyl)tetrahydrofuran-3,4-diol
• 英文别名: (3R,4R,5R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-5-[(1R)-1,2-dihydroxyethyl]oxolane-3,4-diol
• CAS: 2271248-78-1
• 化学式: C₂₁H₂₅ClO₆
• 分子量: 408.879
• InChiKey: RRYZEJFQBYDTNH-ISCVKXCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  99.4
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  达格列净杂质14 在 4-二甲氨基吡啶 、 sodium methylate 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 6.0h， 生成 (1S)-1,4-anhydro-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-D-glucitol
  参考文献：
  名称：

  Synthesis and biological evaluation of novel C-aryl d-glucofuranosides as sodium-dependent glucose co-transporter 2 inhibitors

  摘要：

  Novel C-aryl-D-glucofuranosides were synthesized and evaluated for their capacity to inhibit human sodium-dependent glucose co-transporter 2 (hSGLT2) and hSGLT1. Compound 21q demonstrated the best in vitro inhibitory activity against SGLT2 in this series (EC50 = 0.62 mu M). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.067
• 作为产物：
  描述：

  (5-溴-2-氯苯基)(4-乙氧苯基)甲酮 在 三乙基硅烷 、 正丁基锂 、 三氟化硼乙醚 、 乙硫醇 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 25.0h， 生成 达格列净杂质14
  参考文献：
  名称：

  Synthesis and biological evaluation of novel C-aryl d-glucofuranosides as sodium-dependent glucose co-transporter 2 inhibitors

  摘要：

  Novel C-aryl-D-glucofuranosides were synthesized and evaluated for their capacity to inhibit human sodium-dependent glucose co-transporter 2 (hSGLT2) and hSGLT1. Compound 21q demonstrated the best in vitro inhibitory activity against SGLT2 in this series (EC50 = 0.62 mu M). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.067

文献信息

• Discovery of Dapagliflozin: A Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes
  作者：Wei Meng、Bruce A. Ellsworth、Alexandra A. Nirschl、Peggy J. McCann、Manorama Patel、Ravindar N. Girotra、Gang Wu、Philip M. Sher、Eamonn P. Morrison、Scott A. Biller、Robert Zahler、Prashant P. Deshpande、Annie Pullockaran、Deborah L. Hagan、Nathan Morgan、Joseph R. Taylor、Mary T. Obermeier、William G. Humphreys、Ashish Khanna、Lorell Discenza、James G. Robertson、Aiying Wang、Songping Han、John R. Wetterau、Evan B. Janovitz、Oliver P. Flint、Jean M. Whaley、William N. Washburn

  DOI：10.1021/jm701272q

  日期：2008.3.13

  C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.

  C-芳基葡糖苷6（dapagliflozin）被确定为有效的选择性hSGLT2抑制剂，在高血糖链脲佐菌素（STZ）大鼠中，它以剂量依赖性方式降低了55％的血糖水平。这些发现与良好的ADME谱相结合，已促使达格列净治疗2型糖尿病的临床评估得到了评价。
• A Concise and Efficient Synthesis of Dapagliflozin
  作者：Jun Yu、Ying Cao、HaiZhou Yu、JinJia Wang

  DOI：10.1021/acs.oprd.9b00141

  日期：2019.7.19

  A concise and efficient synthesis of the SGLT-2 inhibitor dapagliflozin (1) has been developed. This route involves ethyl C-aryl glycoside 9 as the key intermediate, which is easily crystallized and purified as the crystalline n-propanol solvate with high purity (>98.5%). The tetra-O-unprotected compound 9 could be directly reduced to crude dapagliflozin with high diastereoselectivity. The final pure

  已经开发了简洁高效的SGLT-2抑制剂dapagliflozin（1）的合成方法。该途径涉及作为主要中间体的乙基C-芳基糖苷9，其易于结晶和纯化为高纯度（> 98.5％）的结晶正丙醇溶剂化物。四-O-未保护的化合物9可以高非对映选择性地直接还原为粗制的达格列净。分离出最终的纯API产物1，并以高纯度（> 99.7％）进行纯化。该过程已在多千克规模上实施。
• [EN] ISOLATED INTERMEDIATE OF DAPAGLIFLOZIN, PROCESS FOR THE PREPARATION OF ISOLATED INTERMEDIATE OF DAPAGLIFLOZIN, PROCESS FOR THE PREPARATION OF DAPAGLIFLOZIN<br/>[FR] INTERMÉDIAIRE ISOLÉ DE DAPAGLIFLOZINE, PROCÉDÉ DE PRÉPARATION D'UN INTERMÉDIAIRE ISOLÉ DE DAPAGLIFLOZINE, PROCÉDÉ DE PRÉPARATION DE DAPAGLIFLOZINE
  申请人：DR REDDY'S LABORATORIES LTD

  公开号：WO2017042683A1

  公开（公告）日：2017-03-16

  Aspects of the present invention relates to an isolated intermediate of Dapagliflozin (Formula III) and its preparation, process for the preparation of Dapagliflozin, process for the preparation of crystalline propane-1,2,3-triol solvate of dapagliflozin, process for the preparation of L-proline complex of Dapagliflozin, solid premix of dapagliflozin with the polymer selected from the group consisting of eudragit, syloid, MCC Avicel PH 102 (1:1) and MCC Avicel PH 102 (1:2).

  本发明的一些方面涉及达帕格列净（Formula III）的分离中间体及其制备，达帕格列净的制备过程，达帕格列净结晶丙烷-1,2,3-三醇溶剂络合物的制备过程，达帕格列净L-脯氨酸络合物的制备过程，以及从Eudragit、Syloid、MCC Avicel PH 102（1:1）和MCC Avicel PH 102（1:2）组成的聚合物中选择的固体达帕格列净预混物的制备过程。
• 一种制备达格列净五元环杂质的方法
  申请人：上海奥博生物医药技术有限公司

  公开号：CN108976182A

  公开（公告）日：2018-12-11

  本发明涉及一种制备达格列净五元环杂质的方法。所述方法通过下面的路线制备，该方法操作简捷安全，收率良好，且产品纯度高。