5-methyl-1-(1-methylethyl)-4-({4-[(1-methylethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl 6-O-(methyloxycarbonyl)-β-D-glucopyranoside

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-methyl-1-(1-methylethyl)-4-({4-[(1-methylethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl 6-O-(methyloxycarbonyl)-β-D-glucopyranoside
• 英文别名: 4-[(4-isopropoxyphenyl)methyl]-1-isopropyl-3-(6-O-methoxy-carbonyl-β-D-glucopyranosyloxy)-5-methylpyrazole；4-(4-isopropoxy-benzyl)-1-isopropyl-5-methyl-3-(6-O-methoxycarbonyl-β-D-glucopyranos-1-yloxy)-1H-pyrazole；methyl [(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[5-methyl-1-propan-2-yl-4-[(4-propan-2-yloxyphenyl)methyl]pyrazol-3-yl]oxyoxan-2-yl]methyl carbonate
• 化学式: C₂₅H₃₆N₂O₉
• 分子量: 508.569
• InChiKey: LABHIKDFEMCEAC-AREVGRJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  [14C]-Remogliflozin 、 二甲基二碳酸盐 在 scandium tris(trifluoromethanesulfonate) 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 0.25h， 以75%的产率得到5-methyl-1-(1-methylethyl)-4-({4-[(1-methylethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl 6-O-(methyloxycarbonyl)-β-D-glucopyranoside
  参考文献：
  名称：

  由三氟甲磺酸钪 (III) 催化介导的未保护吡喃糖衍生物的高选择性初级烷氧基羧化和酯化

  摘要：

  描述了一种用于吡喃糖衍生物的伯醇的烷氧基羧化和酰化的高选择性方法。该反应产率高，在温和条件下进行，0.15-1 mol-% Sc(OTf)3 与酸酐或焦碳酸盐结合使用，温度为 40-50 °C。观察到的未保护吡喃糖衍生物的烷氧基羧化选择性 > 95%，这构成了优于现有方法的显着优势。还讨论了机械影响，包括空间需求和金属-杂原子配位的作用。

  DOI：

  10.1002/ejoc.201200261

文献信息

• Glucopyranosyloxypyrazole derivatives and use thereof in medicines
  申请人：Fujikura Hideki

  公开号：US20060094667A1

  公开（公告）日：2006-05-04

  The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R represents a hydrogen atom, a lower alkyl group or a group forming a prodrug;.one of Q and T represents a group represented by the general formula: (wherein P represents a hydrogen atom or a group forming a prodrug), while the other represents a lower alkyl group or a halo(lower alkyl) group; R 2 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo (lower alkyl) group or a halogen atom; and with the proviso that P does not represent a hydrogen atom when R represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, which exert an inhibitory activity in human SGLT2 and have an improved oral absorption, and therefore are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutically acceptable salts thereof, and pharmaceutical uses thereof.

  本发明提供了由下式表示的葡萄糖吡唑衍生物： 其中，R表示氢原子，低级烷基或形成前药的基团；Q和T中的一个表示由下式表示的基团： （其中，P表示氢原子或形成前药的基团），而另一个表示低级烷基或卤代（低级烷基）基团；R2表示氢原子，低级烷基，低级烷氧基，低级烷基硫基，卤代（低级烷基）基团或卤素原子；但要注意，当R表示氢原子或低级烷基时，P不表示氢原子。本发明的衍生物在人体SGLT2中具有抑制活性，并具有改善口服吸收，因此可用作预防或治疗与高血糖有关的疾病，如糖尿病、糖尿病并发症或肥胖症的药物，以及其药学上可接受的盐和药物用途。
• Glucopyranosyloxyprazole derivatives and use thereof in medicines
  申请人：Fujikura Hideki

  公开号：US20060035847A1

  公开（公告）日：2006-02-16

  The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R represents a hydrogen atom, a lower alkyl group or a group forming a prodrug; one of Q and T represents a group represented by the general formula: (wherein P represents a hydrogen atom or a group forming a prodrug), while the other represents a lower alkyl group or a halo(lower alkyl) group; R 2 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo (lower alkyl) group or a halogen atom; and with the proviso that P does not represent a hydrogen atom when R represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, which exert an inhibitory activity in human SGLT2 and have an improved oral absorption, and therefore are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutically acceptable salts thereof, and pharmaceutical uses thereof.

  本发明提供了由下式表示的葡萄糖吡唑基氧基吡唑衍生物： 其中R表示氢原子、低碳基或形成前药的基团；Q和T中的一个表示由下式表示的基团： （其中P表示氢原子或形成前药的基团），而另一个表示低碳基或卤代（低碳基）基团；R2表示氢原子、低碳基、低碳氧基基团、低碳硫基基团、卤代（低碳基）基团或卤素原子；但是在R表示氢原子或低碳基团时，P不表示氢原子。此类衍生物在人类SGLT2中具有抑制活性，并具有改善口服吸收，因此可用作预防或治疗与高血糖有关的疾病，如糖尿病、糖尿病并发症或肥胖症的药物，以及其医药用途的药物可接受的盐。
• Methods for preventing and treating metabolic disorders and new pyrazole-O-glycoside derivatives
  申请人：Himmelsbach Frank

  公开号：US20070072813A1

  公开（公告）日：2007-03-29

  The invention relates to methods for preventing or treating metabolic disorders, for improving glycemic control, for preventing progression from impaired glucose tolerance, insulin resistance and/or from metabolic syndrome to type 2 diabetes mellitus, for preventing or treating of complications of diabetes mellitus, for reducing the weight, for preventing or treating the degeneration of pancreatic beta cells, for treating hyperinsulinemia and insulin resistance and diabetes type 1, in patients in need thereof by administering a pharmaceutical composition comprising a pyrazole-O-glycoside as defined in claim 1, or a prodrug thereof, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种预防或治疗代谢性疾病的方法，改善血糖控制，预防从糖耐量受损、胰岛素抵抗和/或代谢综合征进展到2型糖尿病，预防或治疗糖尿病并发症，减轻体重，预防或治疗胰岛β细胞退化，治疗高胰岛素血症和胰岛素抵抗以及1型糖尿病，方法是通过给需要的患者口服含有在权利要求1中定义的吡唑烷-O-糖苷或其前药或其药学上可接受的盐的药物组成物。
• PHARMACEUTICAL COMPOSITION COMPRISING A PYRAZOLE-O-GLUCOSIDE DERIVATIVE
  申请人：Pinnetti Sabine

  公开号：US20100317575A1

  公开（公告）日：2010-12-16

  The invention relates to a pharmaceutical composition comprising a pyrazole-O-glucoside derivative selected from the group of compounds (1) to (29) according to claim 1 in combination with at least one second therapeutic agent which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.

  本发明涉及一种制药组合物，包括根据权利要求1所述的化合物（1）至（29）中选择的吡唑-O-葡萄糖苷衍生物，与至少一种第二治疗剂的组合物，该第二治疗剂适用于治疗或预防选择自1型糖尿病、2型糖尿病、糖耐量受损和高血糖等一个或多个疾病。此外，本发明还涉及预防或治疗代谢紊乱及相关疾病的方法。
• PROGRESSION INHIBITOR FOR DISEASE ATTRIBUTED TO ABNORMAL ACCUMULATION OF LIVER FAT
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1782828A1

  公开（公告）日：2007-05-09

  The present invention provides pharmaceutical compositions useful as agents for the inhibition of progression of diseases associated with abnormal accumulation ofliverlipids. In particular, the pharmaceutical compositions of the present invention which comprise as an active ingredient a sodium/glucose co-transporter 2 inhibitor are highly suitable as an agent for the inhibition of progression of not only common fatty liver but also non-alcholic fatty liver disease (NAFL), non-alcholic steatohepatitis (NASH), hypernutritive fatty liver, diabetic fatty liver, alcholic fatty liver disease toxic fatty liver or the like.

  本发明提供的药物组合物可作为抑制与肝脂异常积聚有关的疾病进展的药物。特别是，本发明的药物组合物包含钠/葡萄糖共转运体 2 抑制剂作为活性成分，非常适合作为不仅是普通脂肪肝，而且是非胆汁性脂肪肝（NAFL）、非胆汁性脂肪性肝炎（NASH）、高营养脂肪肝、糖尿病脂肪肝、胆汁性脂肪肝中毒性脂肪肝或类似疾病的进展抑制剂。