(3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-one | 131757-92-1

• 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: (3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-one
• 英文别名: (3R,4S,5S,6R)-3,4,5-Tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-thiopyran-2-one；(3R,4S,5S,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)thian-2-one
• CAS: 131757-92-1
• 化学式: C₃₄H₃₄O₅S
• 分子量: 554.707
• InChiKey: HNDFNUJGHMMRMV-NXVJRICRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  79.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-one 在 三乙基硅烷 、 正丁基锂 、 三氟化硼乙醚 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 反应 1.25h， 生成 6-(2-chloro-5-((2S,3R,4R,5S,6R)-3,4,5-trisrbenzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-yl)benzyl-2,3-dihydrobenzo[b][1,4]dioxine
  参考文献：
  名称：

  JP5876570

  摘要：

  公开号：
• 作为产物：
  描述：

  五乙酰-5-巯基葡萄糖 在 盐酸 、 硫酸 、 乙酸酐 、 sodium hydride 、 二甲基亚砜 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 53.0h， 生成 (3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-one
  参考文献：
  名称：

  Yuasa, Hideya; Tamura, Jun-ichi; Hashimoto, Hironobu, Journal of the Chemical Society. Perkin transactions I, 1990, # 10, p. 2763 - 2769

  摘要：

  DOI：

文献信息

• THIOGLUCOSE SPIROKETAL DERIVATIVE AND USE THEREOF AS THERAPEUTIC AGENT FOR DIABETES
  申请人：Sato Tsutomu

  公开号：US20100093744A1

  公开（公告）日：2010-04-15

  The present invention provides a compound represented by Formula (II): wherein R 1 , R 2 , R 3 , and R 4 are each independently selected from a hydrogen atom, an optionally substituted C 1 -C 6 alkyl group, an optionally substituted C 7 -C 14 aralkyl group and —C(═O)Rx; Rx is an optionally substituted C 1 -C 6 alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted C 1 -C 6 alkoxy group or —NReRf; Ar 1 is an optionally substituted aromatic carbocyclic ring, or an optionally substituted aromatic heterocyclic ring which may form a condensed ring; Q is —(CH 2 ) m -(L) p - or -(L) p -(CH 2 ) m —; m is an integer selected from 0 to 2, n is an integer selected from 1 and 2, and p is an integer selected from 0 and 1; L is —O—, —S— or —NR 5 —; A is an optionally substituted aryl group or an optionally substituted heteroaryl group; and a prodrug thereof and a pharmaceutically acceptable salt thereof, and a pharmaceutical agent or a pharmaceutical composition, which comprises the compound.

  本发明提供了一种由Formula (II)表示的化合物：其中R1、R2、R3和R4分别独立地选自氢原子、可选取代的C1-C6烷基、可选取代的C7-C14芳基烷基和—C(═O)Rx；Rx是可选取代的C1-C6烷基、可选取代的芳基、可选取代的杂环芳基、可选取代的C1-C6甲氧基或—NReRf；Ar1是可选取代的芳香环碳环或可选取代的芳香杂环环，可能形成一个融合环；Q是—(CH2)m-(L)p-或-(L)p-(CH2)m—；m是选自0到2的整数，n是选自1和2的整数，p是选自0和1的整数；L是—O—、—S—或—NR5—；A是可选取代的芳基或可选取代的杂环芳基；以及其前体藥物和其藥學上可接受的鹽，以及包含该化合物的藥物代理或藥物组合物。
• C-ARYL GLUCOSIDE DERIVATIVE, PREPARATION METHODS THEREOF, AND MEDICAL APPLICATIONS THEREOF
  申请人：JIANGSU HANSOH PHARMACEUTICAL GROUP CO., LTD.

  公开号：US20160222047A1

  公开（公告）日：2016-08-04

  C-aryl glucoside derivatives, preparation methods thereof, and medical applications thereof are described. Specifically, compounds represented by formula I, and, tautomers, enantiomers, diastereomers, racemates, and pharmaceutically acceptable salts of the compounds, preparation methods thereof, pharmaceutical compositions containing the compounds, and applications thereof are described. Compounds of formula (I) are useful as therapeutic agents, and particularly as sodium-dependent glucose contransporter protein (SGLT) inhibitors.

  本文描述了C-芳基葡萄糖苷衍生物，其制备方法以及医药应用。具体而言，描述了由式I表示的化合物，以及该化合物的互变异构体、对映体、非对映体、拉卡酯和药学上可接受的盐，其制备方法，含有该化合物的药物组合物以及其应用。式(I)的化合物可用作治疗剂，特别是作为钠依赖葡萄糖共转运蛋白（SGLT）抑制剂。
• METHOD FOR PRODUCING DIPHENYLMETHANE DERIVATIVE
  申请人：DAEWOONG PHARMACEUTICAL CO., LTD.

  公开号：US20190169174A1

  公开（公告）日：2019-06-06

  The present invention relates to an improved method for producing a diphenylmethane derivative which is effective as a sodium-dependent glucose cotransporter (SGLT) inhibitor, the method being carried out by means of a convergent synthesis method in which each major group is separately synthesized and then coupled. As such, in comparison to a linear synthesis method disclosed in existing documents, the synthesis pathway is compact and yield can be increased, and risk factors inherent in the linear synthesis pathway can be reduced. Furthermore, the crystal form of the compound produced according to the method has superb physicochemical characteristics, and thus can be effectively utilized in fields such as pharmaceutical manufacturing.

  本发明涉及一种改进的制备二苯甲烷衍生物的方法，该方法作为一种钠依赖型葡萄糖共转运蛋白（SGLT）抑制剂具有高效性，该方法通过收敛合成方法进行，其中每个主要基团分别合成然后耦合。因此，与现有文件披露的线性合成方法相比，合成途径更为紧凑，产率可以提高，并且线性合成途径固有的风险因素可以降低。此外，根据该方法生产的化合物的晶型具有出色的物理化学特性，因此可以有效地应用于制药制造等领域。
• (1<i>S</i>)-1,5-Anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-<scp>d</scp>-glucitol (TS-071) is a Potent, Selective Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for Type 2 Diabetes Treatment
  作者：Hiroyuki Kakinuma、Takahiro Oi、Yuko Hashimoto-Tsuchiya、Masayuki Arai、Yasunori Kawakita、Yoshiki Fukasawa、Izumi Iida、Naoko Hagima、Hiroyuki Takeuchi、Yukihiro Chino、Jun Asami、Lisa Okumura-Kitajima、Fusayo Io、Daisuke Yamamoto、Noriyuki Miyata、Teisuke Takahashi、Saeko Uchida、Koji Yamamoto

  DOI：10.1021/jm901893x

  日期：2010.4.22

  Derivatives of a novel scaffold, C-phenyl 1-thio-d-glucitol, were prepared and evaluated for sodium-dependent glucose cotransporter (SGLT) 2 and SGLT1 inhibition activities. Optimization of substituents on the aromatic rings afforded five compounds with potent and selective SGLT2 inhibition activities. The compounds were evaluated for in vitro human metabolic stability, human serum protein binding

  一种新颖的支架的衍生物，c ^ -苯基-1-硫代d -glucitol，制备并评价为钠依赖性葡萄糖协同转运蛋白（SGLT）2个SGLT1抑制活性。优化芳环上的取代基可得到五种具有有效和选择性SGLT2抑制活性的化合物。评价了这些化合物的体外人类代谢稳定性，人类血清蛋白结合（SPB）和Caco-2渗透性。它们中，（1个小号）-1,5-脱水-1- [5-（4-乙氧基苄基）-2-甲氧基-4-甲基苯基] -1-硫代d -glucitol（3P）显示出强效的SGLT2抑制活性（ IC 50 = 2.26 nM），选择性是SGLT1的1650倍。复合3p对冷冻保存的人肝清除率，较低的SPB和适度的Caco-2通透性显示出良好的代谢稳定性。由于3p应该具有可接受的人体药代动力学（PK）特性，因此它可能是治疗2型糖尿病的临床候选药物。我们观察到化合物3p在动物中表现出降血糖作用，出色的尿葡萄糖排泄特性和有
• 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。