GSK279782 | 329044-79-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: GSK279782
• 英文别名: 4-(4-isopropoxybenzyl)-5-methyl-1H-pyrazol-3-yl β-D-glucopyranoside；3-(β-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)-methyl]-5-methyl-1H-pyrazole；4-[(4-isopropoxyphenyl)methyl]-5-methyl-1H-pyrazole-3-O-β-D-glucopyranoside；3-(beta-D-glucopyranosyloxy)-4-[(4-iso-propoxyphenyl)methyl]-5-methyl-1H-pyrazole；(2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[[5-methyl-4-[(4-propan-2-yloxyphenyl)methyl]-1H-pyrazol-3-yl]oxy]oxane-3,4,5-triol
• CAS: 329044-79-3
• 化学式: C₂₀H₂₈N₂O₇
• 分子量: 408.452
• InChiKey: YQFYTOQBHMPXFY-NUABRCLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  137
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  GSK279782 在 sodium iodide 2,4,6-三甲基吡啶 、 caesium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 72.0h， 生成 1-(cyclopropylmethyl)-3-(6-O-ethoxycarbonyl-β-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)methyl]-5-methyl-1H-pyrazole
  参考文献：
  名称：

  GLYCOPYRANOSYLOXYPYRAZOLE DERIVATIVES AND MEDICINAL USE THEREOF

  摘要：

  公开号：

  EP1364957B1
• 作为产物：
  描述：

  methyl 2-(4-isopropoxybenzyl)-3-oxobutanoate 在 sodium hydroxide 、 silver carbonate 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 为溶剂， 反应 2.0h， 生成 GSK279782
  参考文献：
  名称：

  GLYCOPYRANOSYLOXYPYRAZOLE DERIVATIVES AND MEDICINAL USE THEREOF

  摘要：

  公开号：

  EP1364957B1

文献信息

• Discovery of remogliflozin etabonate: A potent and highly selective SGLT2 inhibitor
  作者：Kazuo Shimizu、Hideki Fujikura、Nobuhiko Fushimi、Toshihiro Nishimura、Kazuya Tatani、Kenji Katsuno、Yoshikazu Fujimori、Shinjiro Watanabe、Masahiro Hiratochi、Takeshi Nakabayashi、Noboru Kamada、Koichi Arakawa、Hidemasa Hikawa、Isao Azumaya、Masayuki Isaji

  DOI：10.1016/j.bmc.2021.116033

  日期：2021.3

  after oral administration, to improve selectivity for SGLT2 and oral bioavailability. O-glucoside derivative 24 (remogliflozin etabonate) was subsequently identified as a potent, highly selective, and orally available SGLT2 inhibitor.

  我们优化了口服给药后从小鼠尿液中获得的 WAY-123783活性代谢物(1)的结构，以提高对 SGLT2 的选择性和口服生物利用度。O-葡萄糖苷衍生物24（remogliflozin etabonate）随后被鉴定为一种有效的、高选择性的、可口服的 SGLT2 抑制剂。
• 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。
• Glucopyranosyloxypyrazole derivatives, medicinal compositions containing the same and intermediates in the production thereof
  申请人：Fujikura Hideki

  公开号：US20050261206A1

  公开（公告）日：2005-11-24

  The present invention relates to glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R 1 represents a hydrogen atom or a lower alkyl group; one of Q 1 and T 1 represents a group represented by the general formula: while the other represents a lower alkyl group or a halo(lower alkyl) group; and 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, or pharmaceutically acceptable salts thereof, which have an inhibitory activity in human SGLT2 and are useful as agents for the prevention or treatment of diabetes, diabetic complications or obesity, and to pharmaceutical compositions comprising the same and intermediates thereof.

  本发明涉及由下式表示的葡萄糖吡唑衍生物：其中R1代表氢原子或低碳基；Q1和T1中的一个代表由下式表示的基团：另一个代表低碳基或卤代（低碳）基团；R2代表氢原子、低碳基、低烷氧基、低烷硫基、卤代（低碳）基团或卤素原子，或其药学上可接受的盐，具有对人类SGLT2的抑制活性，并且可用作预防或治疗糖尿病、糖尿病并发症或肥胖症的药物，以及包含它们和它们的中间体的制药组合物。
• Glucopyranosyloxypyrazole derivatives and medicinal use thereof
  申请人：Nishimura Toshihiro

  公开号：US20060142209A1

  公开（公告）日：2006-06-29

  The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein one of Q and T represents a group represented by the general formula: while the other represents a lower alkyl group or a halo(lower alkyl) group; R 1 represents a hydrogen atom, an optionally substituted lower alkyl group, a lower alkenyl group, a cyclic lower alkyl group, etc.; R 2 represents a hydrogen atom, an optionally substituted lower alkyl group, a lower alkoxy group, a lower alkenyl group, a cyclic lower alkyl group, a cyclic lower alkoxy group, etc., which exert an excellent inhibitory activity in human SGLT2, and therefore are useful as drugs for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, pharmaceutically acceptable salts thereof or prodrugs thereof, production intermediates thereof and pharmaceutical uses thereof.

  本发明提供一种由下式表示的葡萄糖吡唑衍生物：其中Q和T中的一个表示由下式表示的基团：而另一个表示较低的烷基或卤代（较低的烷基）基团；R1表示氢原子、可选地取代的较低烷基基团、较低烯基基团、环状较低烷基基团等；R2表示氢原子、可选地取代的较低烷基基团、较低烷氧基基团、较低烯基基团、环状较低烷基基团、环状较低烷氧基基团等，这些化合物在人类SGLT2中表现出优异的抑制活性，因此可用作预防或治疗与高血糖相关的疾病，如糖尿病、糖尿病并发症或肥胖症的药物，其药学上可接受的盐或前药，其生产中间体以及其制药用途。
• Glycopyranosyloxypyrazole derivatives and medicinal use thereof
  申请人：——

  公开号：US20040132669A1

  公开（公告）日：2004-07-08

  The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: 1 wherein one of Q and T represents a group represented by the general formula: 2 while the other represents a lower alkyl group or a halo(lower alkyl) group; R 1 represents a hydrogen atom, an optionally substituted lower alkyl group, a lower alkenyl group, a cyclic lower alkyl group, etc.; R 2 represents a hydrogen atom, an optionally substituted lower alkyl group, a lower alkoxy group, a lower alkenyl group, a cyclic lower alkyl group, a cyclic lower alkoxy group, etc., which exert an excellent inhibitory activity in human SGLT2, and therefore are useful as drugs for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, pharmaceutically acceptable salts thereof or prodrugs thereof, production intermediates thereof and pharmaceutical uses thereof.

  本发明提供了一种由通式1表示的葡萄糖吡唑衍生物，其中Q和T中的一个表示由通式2表示的基团，而另一个表示较低的烷基基团或卤代（较低的烷基）基团；R1表示氢原子、可选取代的较低烷基基团、较低烯基基团、环状较低烷基基团等；R2表示氢原子、可选取代的较低烷基基团、较低烷氧基团、较低烯基基团、环状较低烷基基团、环状较低烷氧基团等。这些衍生物在人类SGLT2中具有出色的抑制活性，因此可用作预防或治疗与高血糖相关的疾病，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或前药、生产中间体及其制药用途。