5-乙基-4,5,6,7-四氢噻唑并[5,4-c]吡啶-2-胺 | 17899-49-9

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 5-乙基-4,5,6,7-四氢噻唑并[5,4-c]吡啶-2-胺
• 中文别名: 5-乙基-4,5,6,7-四氢-噻唑并[5,4-C]吡啶-2-胺
• 英文名称: 2-amino-5-ethyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine
• 英文别名: 5-ethyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-ylamine；5-Ethyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-ylamine；5-ethyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-amine
• CAS: 17899-49-9
• 化学式: C₈H₁₃N₃S
• mdl: MFCD02724251
• 分子量: 183.277
• InChiKey: MSKNCRMLUUGTDB-UHFFFAOYSA-N

物化性质

• 沸点：
  327.2±32.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)
• 溶解度：
  25.8 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.625
• 拓扑面积：
  70.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3-((1-methoxypropan-2-yl)oxy)-5-(4-(methylsulfonyl)phenoxy)benzoic acid 、 5-乙基-4,5,6,7-四氢噻唑并[5,4-c]吡啶-2-胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以36%的产率得到N-(5-ethyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)-3-((1-methoxypropan-2-yl)oxy)-5-(4-(methylsulfonyl)phenoxy)benzamide
  参考文献：
  名称：

  Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation

  摘要：

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.051
• 作为产物：
  描述：

  N-乙基-4-哌啶酮 、 氰胺 在 四氢吡咯 、 sulfur 作用下， 以 异丙醇 为溶剂， 反应 8.0h， 以59%的产率得到5-乙基-4,5,6,7-四氢噻唑并[5,4-c]吡啶-2-胺
  参考文献：
  名称：

  Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation

  摘要：

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.051

文献信息

• PHARMACEUTICAL COMPOUNDS
  申请人：Congreve Miles Stuart

  公开号：US20100004243A1

  公开（公告）日：2010-01-07

  The invention provides a cyclin dependent kinase (e.g. cdk-4 kinase) inhibitor of the formula (I) or a salt, tautomer, solvate or N-oxide thereof; wherein R 1 is an optionally substituted monocyclic or bicyclic aryl or heteroaryl group containing 0-2 heteroatoms selected from O, N and S wherein the optional substituents are selected from halogen, C 1-4 alkyl, C 1-4 alkoxy, C 3-4 cycloalkyl and cyano, and wherein the C 1-4 alkyl and C 1-4 alkoxy groups are each optionally further substituted by C 1-2 alkoxy or one or more halogen atoms; and E is a group E1, E2, E3 or E4: formulae E1, E2, E3, E4 wherein n, q, A5 B, T, U, V, W, Z, R 2 , R 5 , R 6 and R 7 are as defined in the claims.

  该发明提供了一种公式（I）的细胞周期依赖性激酶（例如cdk-4激酶）抑制剂或其盐，互变异构体，溶剂化合物或N-氧化物；其中R1是一个含有0-2个来自O，N和S的杂原子的可选取代的单环或双环芳基或杂芳基基团，其中可选的取代基被选自卤素，C1-4烷基，C1-4烷氧基，C3-4环烷基和氰基，其中C1-4烷基和C1-4烷氧基基团可以进一步被C1-2烷氧基或一个或多个卤素原子取代；而E是E1，E2，E3或E4的基团：公式E1，E2，E3，E4其中n，q，A5 B，T，U，V，W，Z，R2，R5，R6和R7如权利要求中所定义。
• PROCESS FOR PREPARING COMPOUND BY NOVEL SANDMEYER-LIKE REACTION USING NITROXIDE RADICAL COMPOUND AS REACTION CATALYST
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2602242A1

  公开（公告）日：2013-06-12

  The present invention provides a novel process for preparing a substituted aromatic compound such as an aromatic halo compound or a salt thereof through a transformation reaction of an aromatic diazonium salt from an aromatic amino compound at stable high yields utilizing a novel Sandmeyer-like reaction using a nitroxide radical compound as a reaction catalyst.

  本发明提供了一种新工艺，利用一种新型桑德迈尔类反应，以硝基自由基化合物为反应催化剂，通过芳香族重氮盐与芳香族氨基化合物的转化反应，以稳定的高产率制备取代的芳香族化合物，如芳香族卤代化合物或其盐。
• [EN] N-SUBSTITUTED-3,5-DISUBSTITUTED BENZAMIDE COMPOUND AND PREPARATION METHOD AND APPLICATION THEREOF<br/>[FR] COMPOSÉ BENZAMIDE N-SUBSTITUÉ-3,5-DISUBSTITUÉ ET SES PROCÉDÉ DE PRÉPARATION ET APPLICATION<br/>[ZH] N-取代-3,5-二取代苯甲酰胺类化合物及其制备方法和应用
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2016112863A1

  公开（公告）日：2016-07-21

  本发明公开一种N-取代-3,5-二取代苯甲酰胺类化合物及其制备方法和应用，该化合物结构如通式I所示，式中，m、X、Y、R1、R2和R3如权利要求书和说明书所示。本发明还公开了包含通式I所示化合的药物组合物。本发明的化合物可以作为葡萄糖激酶激动剂，用于预防和/或治疗与葡萄糖代谢异常相关的疾病。