5-苄基-4,5,6,7-四氢-噻唑并[5,4-c]吡啶-2-胺 | 327077-32-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-苄基-4,5,6,7-四氢-噻唑并[5,4-c]吡啶-2-胺
• 英文名称: 2-amino-5-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine
• 英文别名: 5-Benzyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-ylamine；5-benzyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-amine
• CAS: 327077-32-7
• 化学式: C₁₃H₁₅N₃S
• mdl: MFCD02654177
• 分子量: 245.348
• InChiKey: MEEFMSOSTHOISQ-UHFFFAOYSA-N

物化性质

• 沸点：
  414.1±40.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  70.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-苄基-4,5,6,7-四氢-噻唑并[5,4-c]吡啶-2-胺 在 盐酸 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 tin(ll) chloride 作用下， 以 甲醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 48.67h， 生成 (R)-N-[4-(7-benzyl-5,6,7,8-tetrahydroimidazo[2',1':2,3]thiazolo[5,4-c]pyridin-2-yl)phenyl]-2-[2-(3,5-dimethylphenyl)acetamido]-3-phenylpropanamide
  参考文献：
  名称：

  Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling

  摘要：

  The Met receptor tyrosine kinase is a promising target in anticancer therapies for its role during tumor evolution and resistance to treatment. It is characterized by an unusual structural plasticity as its active site accepts different inhibitor binding modes. Such feature can be exploited to identify distinct agents targeting tumor dependence and/or resistance by oncogenic Met. Here we report the identification of bioactive agents, featuring a new 4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl moiety, targeting cancer cells dependent on oncogenic Met. One of these compounds (7c; Triflorcas) impairs survival, anchorage-independent growth, and in vivo tumorigenesis, without showing side effects. Our medicinal chemistry strategy was based on an in-house Met-focused library of aminoacid-amide derivatives enriched through structure-based computer modeling, taking into account the Met multiple-binding-mode feature. Altogether, our findings show how a rational structure-based drug design approach coupled to cell-based drug evaluation strategies can be applied in medicinal chemistry to identify new agents targeting a given oncogenic-dependency setting. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.051
• 作为产物：
  描述：

  N-苄基哌啶酮 、 氰胺 在 四氢吡咯 、 sulfur 作用下， 以 异丙醇 为溶剂， 反应 8.0h， 以96%的产率得到5-苄基-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

• Thiazolopyridines Improve Adipocyte Function by Inhibiting 11 Beta-HSD1 Oxoreductase Activity
  作者：Thirumurugan Rathinasabapathy、Kimberly Marie Palatini Jackson、Yiwen Thor、Ayuba Sunday Buru、Debora Esposito、Xu Li、Mallikarjuna Rao Pichika、Ahmad Sazali Hamzah、Slavko Komarnytsky

  DOI：10.1155/2017/3182129

  日期：——

  Background. Glucocorticoid excess has been linked to clinical observations associated with the pathophysiology of metabolic syndrome. The intracellular glucocorticoid levels are primarily modulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme that is highly expressed in key metabolic tissues including fat, liver, and the central nervous system. Methods. In this study we synthesized

  背景。糖皮质激素过量与代谢综合征病理生理学相关的临床观察有关。细胞内糖皮质激素水平主要由 11β-羟基类固醇脱氢酶 1 (11β-HSD1) 酶调节，该酶在包括脂肪、肝脏和中枢神经系统在内的关键代谢组织中高度表达。方法。在这项研究中，我们合成了一组新的四氢噻唑并吡啶衍生物 TR-01-4，它们专门针对 11β-HSD1，并研究了它们干扰 3T3-L1 脂肪细胞中糖皮质激素和脂质代谢的能力。结果。基于对接模型和构效关系，四氢噻唑并吡啶衍生物 TR-02 和 TR-04 通过剂量依赖性抑制可的松向皮质醇的转化显示出最高的抗 11β-HSD1 效力（IC50 值分别为 1.8 μM 和 0.095 μM）。用 0.1-10 μM TR-01-4 孵育脂肪细胞可显着降低可的松诱导的脂肪细胞脂质积累并抑制 11β-HSD1 mRNA 表达。观察到的脂肪细胞脂肪储存减少可以部分解释为脂肪生成标志物（P
• [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。
• Amat, Mercedes; Koever, Andrea; Jokic, Danica, ARKIVOC, 2010, vol. 2010, # 3, p. 145 - 151
  作者：Amat, Mercedes、Koever, Andrea、Jokic, Danica、Lozano, Oscar、Perez, Maria、Landoni, Nicola、Subrizi, Fabiana、Bautista, Jesus、Bosch, Joan

  DOI：——

  日期：——
• Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-N-thiazolyl-oxirane-2-carboxamides as glucokinase activators
  作者：Na Ye、Xiangtao Xu、Fuying Li、Mengmeng Ning、Zhiqing Liu、Yuqing Cao、Ying Leng、Ao Zhang

  DOI：10.1016/j.tetlet.2012.06.111

  日期：2012.8

  RuCl3/NaIO4-initiated oxidation of oxiranemethanols was investigated, and two products, oxirane-2-carboxylic acid and (5'-oxotetrahydrofuran-3-yl)acetic acid, were obtained in variant ratios. The product structures were determined and a tentative mechanism involving oxidation-rearrangement-oxidation process was proposed. Glucokinase enzymatic assay revealed that oxiranecarboxamides 4a-c retained moderate GK activation potency with amide 4a showing an EC50 value of 584 nM and a high activation fold of 3.14. However, (5'-oxotetrahydrofuran-3-yl)acetamide ha is inactive. This study not only provided an alternative protocol to access (5'-oxotetrahydrofuran-3-yl)acetic acid analogs, but also yielded nanomolar GA activators (esp. 4a) for further structure-activity relationship study. (C) 2012 Elsevier Ltd. All rights reserved.
• Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling
  作者：Alessandro Furlan、Francesco Colombo、Andrea Kover、Nathalie Issaly、Cristina Tintori、Lucilla Angeli、Vincent Leroux、Sébastien Letard、Mercedes Amat、Yasmine Asses、Bernard Maigret、Patrice Dubreuil、Maurizio Botta、Rosanna Dono、Joan Bosch、Oreste Piccolo、Daniele Passarella、Flavio Maina

  DOI：10.1016/j.ejmech.2011.10.051

  日期：2012.1

  The Met receptor tyrosine kinase is a promising target in anticancer therapies for its role during tumor evolution and resistance to treatment. It is characterized by an unusual structural plasticity as its active site accepts different inhibitor binding modes. Such feature can be exploited to identify distinct agents targeting tumor dependence and/or resistance by oncogenic Met. Here we report the identification of bioactive agents, featuring a new 4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl moiety, targeting cancer cells dependent on oncogenic Met. One of these compounds (7c; Triflorcas) impairs survival, anchorage-independent growth, and in vivo tumorigenesis, without showing side effects. Our medicinal chemistry strategy was based on an in-house Met-focused library of aminoacid-amide derivatives enriched through structure-based computer modeling, taking into account the Met multiple-binding-mode feature. Altogether, our findings show how a rational structure-based drug design approach coupled to cell-based drug evaluation strategies can be applied in medicinal chemistry to identify new agents targeting a given oncogenic-dependency setting. (C) 2011 Elsevier Masson SAS. All rights reserved.