4-(4-benzyloxy-2-methylphenylmethyl)-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one | 661481-04-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(4-benzyloxy-2-methylphenylmethyl)-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one
• 英文别名: 4-[(4-benzyloxy-2-methylphenyl)methyl]-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one；4-[(2-methyl-4-phenylmethoxyphenyl)methyl]-5-propan-2-yl-1,2-dihydropyrazol-3-one
• CAS: 661481-04-5
• 化学式: C₂₁H₂₄N₂O₂
• 分子量: 336.434
• InChiKey: VUQGNQFOIKPQEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-benzyloxy-2-methylphenylmethyl)-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one 在 甲醇 、 palladium 10% on activated carbon 、 氢气 、 sodium methylate 、 苄基三丁基氯化铵 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 4-(4-hydroxy-2-methylphenylmethyl)-5-isopropyl-1H-pyrazol-3-yl β-d-glucopyranoside
  参考文献：
  名称：

  Structure–activity relationship studies of 4-benzyl-1H-pyrazol-3-yl β-d-glucopyranoside derivatives as potent and selective sodium glucose co-transporter 1 (SGLT1) inhibitors with therapeutic activity on postprandial hyperglycemia

  摘要：

  Sodium glucose co-transporter 1 (SGLT1) plays a dominant role in the absorption of glucose in the gut and is considered a promising target in the development of treatments for postprandial hyperglycemia. A series of 4-benzyl-1H-pyrazol-3-yl beta-D-glucopyranoside derivatives have been synthesized, and its inhibitory activity toward SGLTs has been evaluated. By altering the substitution groups at the 5-position of the pyrazole ring, and every position of the phenyl ring, we studied the structure-activity relationship (SAR) profiles and identified a series of potent and selective SGLT1 inhibitors. Representative derivatives showed a dose-dependent suppressing effect on the escalation of blood glucose levels in oral mixed carbohydrate tolerance tests (OCTT) in streptozotocin-nicotinamide-induced diabetic rats (NA-STZ rats). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.037
• 作为产物：
  描述：

  4-苄氧基-2-甲基苯基甲醇 在 sodium hydride 、 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 、 mineral oil 为溶剂， 反应 18.16h， 生成 4-(4-benzyloxy-2-methylphenylmethyl)-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one
  参考文献：
  名称：

  Structure–activity relationship studies of 4-benzyl-1H-pyrazol-3-yl β-d-glucopyranoside derivatives as potent and selective sodium glucose co-transporter 1 (SGLT1) inhibitors with therapeutic activity on postprandial hyperglycemia

  摘要：

  Sodium glucose co-transporter 1 (SGLT1) plays a dominant role in the absorption of glucose in the gut and is considered a promising target in the development of treatments for postprandial hyperglycemia. A series of 4-benzyl-1H-pyrazol-3-yl beta-D-glucopyranoside derivatives have been synthesized, and its inhibitory activity toward SGLTs has been evaluated. By altering the substitution groups at the 5-position of the pyrazole ring, and every position of the phenyl ring, we studied the structure-activity relationship (SAR) profiles and identified a series of potent and selective SGLT1 inhibitors. Representative derivatives showed a dose-dependent suppressing effect on the escalation of blood glucose levels in oral mixed carbohydrate tolerance tests (OCTT) in streptozotocin-nicotinamide-induced diabetic rats (NA-STZ rats). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.037

文献信息

• Pyrazole derivatives, medicinal composition containing the same, medicinal use thereof, and intermediate for production thereof
  申请人：Fushimi Nobuhiko

  公开号：US20050272669A1

  公开（公告）日：2005-12-08

  The present invention provides pyrazole derivatives represented by the general formula: wherein R 1 represents H, an optionally substituted C 1-6 alkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted C 1-6 alkyl group etc.; R 2 represents H, a halogen atom, OH, an optionally substituted C 1-6 alkyl group etc.; X represents a single bond, O or S; Y represents an optionally substituted C 1-6 alkylene group etc.; Z represents —R B , —COR C etc. in which R B represents an optionally substituted C 1-6 alkyl group etc.; and R C represents an optionally substituted C 1-6 alkyl group etc.; R 4 represents H, an optionally substituted C 1-6 alkyl group etc.; and R 3 , R 5 and R 6 represent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, impaired glucose tolerance, impaired fasting glycemia, diabetic complications or obesity, and a disease associated with the increase of blood galactose level such as galactosemia, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.

  本发明提供了由通式表示的吡唑衍生物：其中，R1代表H、可选取代的C1-6烷基等；Q和T中的一个代表由通式表示的基团：或由通式表示的基团：另一个代表可选取代的C1-6烷基等；R2代表H、卤素原子、OH、可选取代的C1-6烷基等；X代表单键、O或S；Y代表可选取代的C1-6亚烷基等；Z代表-RB、-CORC等，其中RB代表可选取代的C1-6烷基等；RC代表可选取代的C1-6烷基等；R4代表H、可选取代的C1-6烷基等；R3、R5和R6代表H、卤素原子等，其药学上可接受的盐或前药，具有在人类SGLT1中出色的抑制活性，可用作预防或治疗与高血糖相关的疾病，如糖尿病、糖耐量受损、空腹血糖受损、糖尿病并发症或肥胖症，以及与血中半乳糖水平增加相关的疾病，如半乳糖血症的治疗剂，以及包含它们的制药组合物、制药用途和制备它们的中间体。
• Pyrazole derivative, medicinal composition containing the same, medicinal use thereof, and intermediate for production thereof
  申请人：Teranishi Hirotaka

  公开号：US20060166899A1

  公开（公告）日：2006-07-27

  The present invention provides pyrazole derivatives represented by the general formula: wherein R 1 represents H, an optionally substituted C 1-6 alkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted C 1-6 alkyl group etc.; R 2 represents H, a halogen atom, OH, an optionally substituted C 1-6 alkyl group etc.; X represents a single bond, O or S; Y represents a single bond, a C 1-6 alkylene group etc.; Z represents CO or SO 2 ; R 4 and R 5 represent H, an optionally substituted C 1-6 alkyl group etc.; and R 3 , R 6 and R 7 represent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.

  本发明提供了由下式表示的吡唑衍生物： 其中，R1代表H、可选取代的C1-6烷基等；Q和T中的一个代表由下式表示的基团： 另一个代表可选取代的C1-6烷基等；R2代表H、卤素原子、OH、可选取代的C1-6烷基等；X代表单键、O或S；Y代表单键、C1-6烷基亚基等；Z代表CO或SO2；R4和R5代表H、可选取代的C1-6烷基等；R3、R6和R7代表H、卤素原子等，其药学上可接受的盐或前药，具有在人类SGLT1中出色的抑制活性，并且作为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，以及包含它们的制药组合物、制药用途和制备它们的中间体。
• PYRAZOLE DERIVATIVES, MEDICINAL COMPOSITION CONTAINING THE SAME, MEDICINAL USE THEREOF, AND INTERMEDIATE FOR PRODUCTION THEREOF
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1548024B1

  公开（公告）日：2012-06-06
• PROCESS FOR PRODUCTION OF GLUCOPYRANOSYLOXYPYRAZOLE DERIVATIVE
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1864993B1

  公开（公告）日：2012-05-16
• PYRAZOLE DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, MEDICINAL USE THEREOF, AND INTERMEDIATE FOR PRODUCTION THEREOF
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1544208B1

  公开（公告）日：2010-05-26