(2S,3R,4R,5S,6R)-2-[5-[(4-bromo-2-methylphenyl)-hydroxymethyl]-2-hydroxy-4-propan-2-ylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol | 1240304-48-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R,4R,5S,6R)-2-[5-[(4-bromo-2-methylphenyl)-hydroxymethyl]-2-hydroxy-4-propan-2-ylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 1240304-48-6
• 化学式: C₂₃H₂₉BrO₇
• 分子量: 497.383
• InChiKey: AXERYXMZKJRJTA-ZOBQWYLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  131
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3R,4R,5S,6R)-2-[5-[(4-bromo-2-methylphenyl)-hydroxymethyl]-2-hydroxy-4-propan-2-ylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol 在 吡啶 、 三乙基硅烷 、 三氟化硼乙醚 、 sodium methylate 、 palladium diacetate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.17h， 生成 (1S)-1,5-anhydro-1-[5-({4-[(1E)-3,3-dimethyl-4-{[2-methyl-1-oxo-1-(piperazin-1-yl)propan-2-yl]amino}-4-oxobut-1-en-1-yl]-2-methylphenyl}methyl)-2-hydroxy-4-(propan-2-yl)phenyl]-D-glucitol
  参考文献：
  名称：

  Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment

  摘要：

  A new series of C-phenyl D-glucitol derivatives was designed and synthesized, and their SGLT1 inhibitory potency and absorbability were evaluated. We also investigated whether kidney drug retention could be avoided by creating molecules with different excretion pathways. To achieve a class of molecules with low absorption and that were excreted in bile, optimized synthesis was performed to bring the ClogP value and the topological polar surface area to within the appropriate ranges. Compounds 34d and 34j were poorly absorbed, but the absorbed compounds were mainly excreted in bile. Thus, smaller amounts of persistent residue in the kidneys were observed. Since 34d exerted a glucose-lowering effect at a dose of 0.3 mg/kg (p.o.) in SD rats, this compound (SGL5213) could be a clinical candidate for the treatment of type 2 diabetes.

  DOI：

  10.1016/j.bmc.2018.12.015
• 作为产物：
  描述：

  3-异丙基苯酚 在 吡啶 、 三乙基硅烷 、 4-二甲氨基吡啶 、 potassium iodate 、 正丁基锂 、 甲烷磺酸 、 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 、 溴 、 碘 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 102.25h， 生成 (2S,3R,4R,5S,6R)-2-[5-[(4-bromo-2-methylphenyl)-hydroxymethyl]-2-hydroxy-4-propan-2-ylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
  参考文献：
  名称：

  Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment

  摘要：

  A new series of C-phenyl D-glucitol derivatives was designed and synthesized, and their SGLT1 inhibitory potency and absorbability were evaluated. We also investigated whether kidney drug retention could be avoided by creating molecules with different excretion pathways. To achieve a class of molecules with low absorption and that were excreted in bile, optimized synthesis was performed to bring the ClogP value and the topological polar surface area to within the appropriate ranges. Compounds 34d and 34j were poorly absorbed, but the absorbed compounds were mainly excreted in bile. Thus, smaller amounts of persistent residue in the kidneys were observed. Since 34d exerted a glucose-lowering effect at a dose of 0.3 mg/kg (p.o.) in SD rats, this compound (SGL5213) could be a clinical candidate for the treatment of type 2 diabetes.

  DOI：

  10.1016/j.bmc.2018.12.015

文献信息

• 4-ISOPROPYLPHENYL GLUCITOL COMPOUNDS AS SGLT1 INHIBITORS
  申请人：Kakinuma Hiroyuki

  公开号：US20110306759A1

  公开（公告）日：2011-12-15

  The present invention provides 4-isopropylphenyl glucitol compounds which have no tendency to accumulate in the body and which inhibit SGLT1 activity to suppress postprandial hyperglycemia (or impaired glucose tolerance) through suppression of glucose absorption in the small intestine, whereby the compounds, for example, can suppress the onset of diabetes and metabolic syndrome or can treat these diseases. A 4-isopropylphenyl glucitol compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: wherein R 1 represents a hydrogen atom, etc., R 2 represents a methyl group, etc., R 3 represents a C 1-4 alkyl group substituted with an amino group(s), etc., and R 4 represents a hydrogen atom, etc.

  本发明提供了4-异丙基苯基葡萄糖醇化合物，其没有在体内积累的趋势，并通过抑制小肠中的葡萄糖吸收来抑制SGLT1活性，从而抑制餐后高血糖（或糖耐量受损），例如，这些化合物可以抑制糖尿病和代谢综合征的发生或治疗这些疾病。化合物由以下式（I）表示：其中R1表示氢原子等，R2表示甲基基团等，R3表示C1-4烷基基团，该基团被氨基团等取代，R4表示氢原子等，或其药学上可接受的盐。
• [EN] 4 -ISOPROPYLPHENYL GLUCITOL COMPOUNDS AS SGLT1 INHIBITORS<br/>[FR] COMPOSÉS DE 4-ISOPROPYLPHÉNYL GLUCITOL COMME INHIBITEURS DE SGLT1
  申请人：TAISHO PHARMA CO LTD

  公开号：WO2010095768A8

  公开（公告）日：2011-08-04
• US8466113B2
  申请人：——

  公开号：US8466113B2

  公开（公告）日：2013-06-18
• Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment
  作者：Shoichi Kuroda、Yohei Kobashi、Takahiro Oi、Kenichi Kawabe、Fumiyasu Shiozawa、Lisa Okumura-Kitajima、Mami Sugisaki-Kitano、Fusayo Io、Koji Yamamoto、Hiroyuki Kakinuma

  DOI：10.1016/j.bmc.2018.12.015

  日期：2019.1

  A new series of C-phenyl D-glucitol derivatives was designed and synthesized, and their SGLT1 inhibitory potency and absorbability were evaluated. We also investigated whether kidney drug retention could be avoided by creating molecules with different excretion pathways. To achieve a class of molecules with low absorption and that were excreted in bile, optimized synthesis was performed to bring the ClogP value and the topological polar surface area to within the appropriate ranges. Compounds 34d and 34j were poorly absorbed, but the absorbed compounds were mainly excreted in bile. Thus, smaller amounts of persistent residue in the kidneys were observed. Since 34d exerted a glucose-lowering effect at a dose of 0.3 mg/kg (p.o.) in SD rats, this compound (SGL5213) could be a clinical candidate for the treatment of type 2 diabetes.