1-(ethoxymethyl)-1H-pyrazol-3-amine | 1480818-27-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 亚胺内酰胺
• 英文名称: 1-(ethoxymethyl)-1H-pyrazol-3-amine
• 英文别名: 1-(ethoxymethyl)pyrazol-3-amine
• CAS: 1480818-27-6
• 化学式: C₆H₁₁N₃O
• 分子量: 141.173
• InChiKey: VHEVOPOHKJZMNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  53.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-methanesulfonylphenoxy)-5-(3-methylpyridin-2-yl)benzoic acid 、 1-(ethoxymethyl)-1H-pyrazol-3-amine 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以52%的产率得到N-(1-ethoxymethyl-1H-pyrazol-3-yl)-3-(4-methanesulfonylphenoxy)-5-(3-methylpyridin-2-yl)benzamide
  参考文献：
  名称：

  Discovery of 3-(4-methanesulfonylphenoxy)-N-[1-(2-methoxy-ethoxymethyl)-1H-pyrazol-3-yl]-5-(3-methylpyridin-2-yl)-benzamide as a novel glucokinase activator (GKA) for the treatment of type 2 diabetes mellitus

  摘要：

  Novel heteroaryl-containing benzamide derivatives were synthesized and screened using an in vitro assay measuring increases in glucose uptake and glucokinase activity stimulated by 10 mM glucose in rat hepatocytes. From a library of synthesized compounds, 3-(4-methanesulfonylphenoxy)-N-[1-(2-methoxy-ethoxymethyl)-1H-pyrazol-3-yl]-5-(3-methyl pyridin-2-yl)-benzamide (19e) was identified as a potent glucokinase activator with assays demonstrating an EC50 of 315 nM and the induction of a 2.23 fold increase in glucose uptake. Compound 19e exhibited a glucose AUC reduction of 32% (50 mg/kg) in an OGTT study with C57BL/6J mice compared to 28% for metformin (300 mg/kg). Single treatment of the compound in C57BL/J6 and ob/ob mice elicited basal glucose lowering activity, while in a two-week repeated dose study with ob/ob mice, the compound significantly decreased blood glucose levels with no evidence of hypoglycemia risk. In addition, 19e exhibited favorable pharmacokinetic parameters in mice and rats and excellent safety margins in liver and testicular toxicity studies. Compound 19e was therefore selected as a development candidate for the potential treatment of type 2 diabetes. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.009

文献信息

• [EN] PHENOXYBENZAMIDE GLUCOKINASE ACTIVATOR CONTAINING NOVEL HETEROARYL AND METHOD FOR PREPARING SAME<br/>[FR] PHÉNOXYBENZAMIDE ACTIVATEUR DE GLUCOKINASE CONTENANT UN NOUVEL HÉTÉROARYLE ET SON PROCÉDÉ DE PRÉPARATION
  申请人：YUHAN CORP

  公开号：WO2014112799A1

  公开（公告）日：2014-07-24

  본 발명은 신규의 헤테로아릴을 포함하는 페녹시벤즈아마이드, 그의 약학적으로 허용 가능한 염, 또는 이들의 수화물 또는 용매화물, 이들의 제조 방법, 및 이들을 포함하는 약학 조성물을 제공한다. 본 발명에 따른 신규의 헤테로아릴을 포함하는 페녹시벤즈아마이드, 그의 약학적으로 허용 가능한 염, 또는 이들의 수화물 또는 용매화물은 글루코키나제를 현저하게 활성화시킴으로써, 고혈당증(hyperglycemia) 및 당뇨병(diabetes)과 같은 글루코키나제 매개 질환의 치료에 유용하게 적용될 수 있다.
• Discovery of 3-(4-methanesulfonylphenoxy)-N-[1-(2-methoxy-ethoxymethyl)-1H-pyrazol-3-yl]-5-(3-methylpyridin-2-yl)-benzamide as a novel glucokinase activator (GKA) for the treatment of type 2 diabetes mellitus
  作者：Kaapjoo Park、Byoung Moon Lee、Kwan Hoon Hyun、Dong Hoon Lee、Hyun Ho Choi、Hyunmi Kim、Wonee Chong、Kyeong Bae Kim、Su Youn Nam

  DOI：10.1016/j.bmc.2014.02.009

  日期：2014.4

  Novel heteroaryl-containing benzamide derivatives were synthesized and screened using an in vitro assay measuring increases in glucose uptake and glucokinase activity stimulated by 10 mM glucose in rat hepatocytes. From a library of synthesized compounds, 3-(4-methanesulfonylphenoxy)-N-[1-(2-methoxy-ethoxymethyl)-1H-pyrazol-3-yl]-5-(3-methyl pyridin-2-yl)-benzamide (19e) was identified as a potent glucokinase activator with assays demonstrating an EC50 of 315 nM and the induction of a 2.23 fold increase in glucose uptake. Compound 19e exhibited a glucose AUC reduction of 32% (50 mg/kg) in an OGTT study with C57BL/6J mice compared to 28% for metformin (300 mg/kg). Single treatment of the compound in C57BL/J6 and ob/ob mice elicited basal glucose lowering activity, while in a two-week repeated dose study with ob/ob mice, the compound significantly decreased blood glucose levels with no evidence of hypoglycemia risk. In addition, 19e exhibited favorable pharmacokinetic parameters in mice and rats and excellent safety margins in liver and testicular toxicity studies. Compound 19e was therefore selected as a development candidate for the potential treatment of type 2 diabetes. (c) 2014 Elsevier Ltd. All rights reserved.