5-methyl-4-(4-methylbenzyl)-1,2-dihydro-3H-pyrazol-3-one

• 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: 5-methyl-4-(4-methylbenzyl)-1,2-dihydro-3H-pyrazol-3-one
• 英文别名: 1,2-dihydro-4-[[4-methylphenyl]methyl]-5-methyl-3H-pyrazol-3-one；1,2-Dihydro-5-methyl-4-[(4-methylphenyl)methyl]-3 H-pyrazol-3-one；1,2-dihydro-5-methyl-4-[(4-methylphenyl)methyl]-3H-pyrazol-3-one；5-methyl-4-[(4-methylphenyl)methyl]-1,2-dihydropyrazol-3-one
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: GFUIHIXCADRSDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methyl-4-(4-methylbenzyl)-1,2-dihydro-3H-pyrazol-3-one 在 甲醇 、 sodium methylate 、 苄基三丁基氯化铵 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 20.0h， 生成 5-methyl-4-(4-methylbenzyl)-1H-pyrazol-3-yl β-D-glucopyranoside
  参考文献：
  名称：

  发现 remogliflozin etabonate：一种有效且高度选择性的 SGLT2 抑制剂

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2021.116033
• 作为产物：
  描述：

  2-(4-methylbenzyl)-3-oxobutyric acid ethyl ester 在 一水合肼 作用下， 以 甲苯 为溶剂， 生成 5-methyl-4-(4-methylbenzyl)-1,2-dihydro-3H-pyrazol-3-one
  参考文献：
  名称：

  发现 remogliflozin etabonate：一种有效且高度选择性的 SGLT2 抑制剂

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2021.116033

文献信息

• O-pyrazole glucoside SGLT2 inhibitors and method of use
  申请人：——

  公开号：US20030087843A1

  公开（公告）日：2003-05-08

  A compound of formula I 1 wherein A is CH 2 or (CH 2 ) 2 ; R 1 is hydrogen, arylalkyl, alkenyl, or alkyl; R2 is alkyl or perfluoroalkyl; and R 3 and R 4 are as defined herein. Further provided are methods of using such compounds for the treatment of diabetes and related diseases, and to pharmaceutical compositions containing such compounds.

  化合物I1的化学式为：其中A为CH2或(CH2)2；R1为氢、芳基烷基、烯丙基或烷基；R2为烷基或全氟烷基；R3和R4的定义如本文所述。还提供了使用这些化合物治疗糖尿病及相关疾病的方法，以及含有这些化合物的制药组合物。
• 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。
• 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。
• GLUCOPYRANOSYLOXYPYRAZOLE DERIVATIVES AND USE THEREOF IN MEDICINES
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1354888B1

  公开（公告）日：2009-05-20