2,3,4,6-tetra-O-benzyl-1-C-[2-(benzyloxy)-4-methyl-5-(4-methylbenzyl)phenyl]-5-thio-D-glucopyranose

• 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: 2,3,4,6-tetra-O-benzyl-1-C-[2-(benzyloxy)-4-methyl-5-(4-methylbenzyl)phenyl]-5-thio-D-glucopyranose
• 英文别名: (3R,4S,5S,6R)-2-[4-methyl-5-[(4-methylphenyl)methyl]-2-phenylmethoxyphenyl]-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)thian-2-ol
• 化学式: C₅₆H₅₆O₆S
• 分子量: 857.123
• InChiKey: BDNLMKZKQLLVCQ-UNXRTQJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.2
• 重原子数：
  63
• 可旋转键数：
  19
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  91.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-benzyl-1-C-[2-(benzyloxy)-4-methyl-5-(4-methylbenzyl)phenyl]-5-thio-D-glucopyranose 在 三乙基硅烷 、 三氟化硼乙醚 作用下， 以 乙醇 、 氯仿 、 乙腈 为溶剂， 生成 (1S)-1,5-anhydro-1-[4-methyl-5-(4-methylbenzyl)-2-hydroxyphenyl]-1-thio-D-glucitol
  参考文献：
  名称：

  Discovery of a potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor (TP0438836) for the treatment of type 2 diabetes

  摘要：

  The design and synthesis of a novel class of low-absorbable SGLT1 inhibitors are described. To achieve low absorption in the new series, we performed an optimization study based on a strategy to increase TPSA. Fortunately, the optimization of an aglycon moiety and a side chain of the distal aglycon moiety led to the identification of compound 30b as a potent and low-absorbable SGLT1 inhibitor. Compound 30b showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose-lowering effect in diabetic rats.

  DOI：

  10.1016/j.bmcl.2018.09.035
• 作为产物：
  描述：

  4-(苄氧基)-5-溴-2-甲基苯甲酸 在 三乙基硅烷 、 正丁基锂 、 草酰氯 、 三氟化硼乙醚 、 magnesium 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 氯仿 、 乙腈 为溶剂， 生成 2,3,4,6-tetra-O-benzyl-1-C-[2-(benzyloxy)-4-methyl-5-(4-methylbenzyl)phenyl]-5-thio-D-glucopyranose
  参考文献：
  名称：

  Discovery of a potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor (TP0438836) for the treatment of type 2 diabetes

  摘要：

  The design and synthesis of a novel class of low-absorbable SGLT1 inhibitors are described. To achieve low absorption in the new series, we performed an optimization study based on a strategy to increase TPSA. Fortunately, the optimization of an aglycon moiety and a side chain of the distal aglycon moiety led to the identification of compound 30b as a potent and low-absorbable SGLT1 inhibitor. Compound 30b showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose-lowering effect in diabetic rats.

  DOI：

  10.1016/j.bmcl.2018.09.035

文献信息

• 1-PHENYL 1-THIO-D-GLUCITOL DERIVATIVE
  申请人：Kakinuma Hiroyuki

  公开号：US20100069460A1

  公开（公告）日：2010-03-18

  A 1-phenyl 1-thio-D-glucitol compound represented by formula (I) or the like: or a pharmaceutically acceptable salt thereof or a hydrate thereof, or a pharmaceutical preparation comprising the same as an active ingredient is useful as a novel type of prophylactic or therapeutic agent for diabetes, diabetes-related diseases or diabetic complications, which inhibits both SGLT1 and SGLT2 activities to achieve not only suppression of glucose absorption from the digestive tract but also excretion of urinary sugars.

  一种由公式（I）或类似物表示的1-苯基1-硫代-D-葡萄糖醇化合物，或其药学上可接受的盐或水合物，或包含其作为活性成分的制药制剂，可用作一种新型的预防或治疗糖尿病、糖尿病相关疾病或糖尿病并发症的药物。该药物不仅抑制消化道中的葡萄糖吸收，还能促进尿糖的排泄，通过同时抑制SGLT1和SGLT2活性来实现。
• EP2103607
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of a potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor (TP0438836) for the treatment of type 2 diabetes
  作者：Shoichi Kuroda、Yohei Kobashi、Takahiro Oi、Hideaki Amada、Lisa Okumura-Kitajima、Fusayo Io、Koji Yamamto、Hiroyuki Kakinuma

  DOI：10.1016/j.bmcl.2018.09.035

  日期：2018.12

  The design and synthesis of a novel class of low-absorbable SGLT1 inhibitors are described. To achieve low absorption in the new series, we performed an optimization study based on a strategy to increase TPSA. Fortunately, the optimization of an aglycon moiety and a side chain of the distal aglycon moiety led to the identification of compound 30b as a potent and low-absorbable SGLT1 inhibitor. Compound 30b showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose-lowering effect in diabetic rats.