tert-butyl 4-(2-chloro-3-nitropyridin-4-yl)piperazine-1-carboxylate | 1314947-09-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(2-chloro-3-nitropyridin-4-yl)piperazine-1-carboxylate
• 英文别名: 4-(2-chloro-3-nitropyridin-4-yl)piperazine-1-carboxylic acid tert-butyl ester
• CAS: 1314947-09-5
• 化学式: C₁₄H₁₉ClN₄O₄
• 分子量: 342.782
• InChiKey: MWZKGVDAUYYWBU-UHFFFAOYSA-N

物化性质

• 沸点：
  486.2±45.0 °C(Predicted)
• 密度：
  1.333±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  91.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-chloro-3-nitropyridin-4-yl)piperazine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 正丁醇 为溶剂， 反应 27.5h， 生成 tert-butyl 4-(3-methyl-2-oxo-1H-imidazo[4,5-b]pyridin-7-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  伊米列汀的发现，一种用于治疗2型糖尿病的新型选择性DPP-4抑制剂。

  摘要：

  我们报告了我们发现的一系列新型的有效和选择性二肽基肽酶IV（DPP-4）抑制剂。从通过脚手架跳跃方法确定的线索开始，我们的发现和开发工作集中在探索结构与活性之间的关系，优化药代动力学特征，改善体外和体内功效以及评估安全性特征。选定的候选人伊米列汀目前正在接受临床试验。

  DOI：

  10.1021/ml5001905
• 作为产物：
  描述：

  2,4-二氯-3-硝基吡啶 、 N-Boc-哌嗪 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 tert-butyl 4-(2-chloro-3-nitropyridin-4-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  伊米列汀的发现，一种用于治疗2型糖尿病的新型选择性DPP-4抑制剂。

  摘要：

  我们报告了我们发现的一系列新型的有效和选择性二肽基肽酶IV（DPP-4）抑制剂。从通过脚手架跳跃方法确定的线索开始，我们的发现和开发工作集中在探索结构与活性之间的关系，优化药代动力学特征，改善体外和体内功效以及评估安全性特征。选定的候选人伊米列汀目前正在接受临床试验。

  DOI：

  10.1021/ml5001905

文献信息

• FUSED PYRIDINE DERIVATIVES
  申请人：Huang Zhenhua

  公开号：US20120289497A1

  公开（公告）日：2012-11-15

  Fused pyridine derivatives shown as the general formula (I), and their pharmaceutically acceptable salts, stereoisomers or solvates thereof are disclosed, which belong to the technical field of medicines. The R 1 , R 2 , R 3 , Q, X and Y substituents in formula (I) are defined as in the description. Also disclosed are the preparation methods, pharmaceutical compositions comprising the compounds and uses of the compounds in the manufacture of the medicine for the treatment and/or prevention of noninsulin-dependent diabetes, hyperglycemia, hyperlipidemia and insulin resistance.

  揭示了作为一般式(I)显示的融合吡啶衍生物以及它们的药用可接受盐、立体异构体或溶剂化物，属于药物技术领域。在式(I)中，R1、R2、R3、Q、X和Y的取代基的定义如描述中所述。还揭示了该化合物的制备方法、包含该化合物的药物组合物以及用于制造治疗和/或预防非胰岛素依赖性糖尿病、高血糖、高脂血症和胰岛素抵抗的药物的用途。
• Fused pyridine derivatives
  申请人：Huang Zhenhua

  公开号：US08680089B2

  公开（公告）日：2014-03-25

  Fused pyridine derivatives shown as the general formula (I), and their pharmaceutically acceptable salts, stereoisomers or solvates thereof are disclosed, which belong to the technical field of medicines. The R1, R2, R3, Q, X and Y substituents in formula (I) are defined as in the description. Also disclosed are the preparation methods, pharmaceutical compositions comprising the compounds and uses of the compounds in the manufacture of the medicine for the treatment and/or prevention of noninsulin-dependent diabetes, hyperglycemia, hyperlipidemia and insulin resistance.

  本发明公开了一种融合吡啶衍生物，其通式为（I），以及其药学上可接受的盐、立体异构体或溶剂化物，属于医药技术领域。式（I）中的R1、R2、R3、Q、X和Y取代基的定义如说明书中所述。同时，本发明还公开了制备方法、包含该化合物的制药组合物以及将该化合物用于制造用于治疗和/或预防非胰岛素依赖性糖尿病、高血糖、高脂血症和胰岛素抵抗的药物的用途。
• Novel non-sulfonamide 5-HT 6 receptor partial inverse agonist in a group of imidazo[4,5- b ]pyridines with cognition enhancing properties
  作者：David Vanda、Miroslav Soural、Vittorio Canale、Séverine Chaumont-Dubel、Grzegorz Satała、Tomasz Kos、Petr Funk、Veronika Fülöpová、Barbora Lemrová、Paulina Koczurkiewicz、Elżbieta Pękala、Andrzej J. Bojarski、Piotr Popik、Philippe Marin、Paweł Zajdel

  DOI：10.1016/j.ejmech.2017.12.053

  日期：2018.1

  A small library of novel 3H-imidazo[4,5-b]pyridine and 1H-imidazo[4,5-c]pyridine derivatives was designed and synthesized as non-sulfonamide 5-HT6 receptor ligands. In vitro evaluation allowed to identify compound 17 (2-ethyl-3-(3-fluorobenzy1)-7-(piperazin-1-yl)-3H-imidazo[4,5-6]pyridine) as potent 5-HT6 receptor partial inverse agonist in G(s) signaling (K-i = 6 nM, IC50=17.6 nM). Compound 17 displayed high metabolic stability, favorable cytochrome P450 isoenzyme (2D6, 3A4) profile, did not affect PgP-protein binding, without evoking mutagenic effects. It was orally bioavailable and brain penetrant. In contrast to intepirdine (SB-742457), which prevented 5-HT6R elicited neurite growth and behaved as an inverse agonist of cyclin-dependent kinase 5 (Cdk5), compound 17 has no influence on neuronal differentiation. Compound 17 exerted significant pro-cognitive properties in novel object recognition (NOR) task in rats reversing both phencyclidine- and scopolamine-induced memory deficits (MED = 1 and 0.3 mg/kg, p.o, respectively). These effects were similar to those produced by intepirdine. Additionally, combination of inactive doses of compound 17 (0.1 mg/kg) and donepezil (0.3 mg/kg) produced synergistic effect to reverse scopolamine-induced memory deficits. Accordingly, investigating putative divergence between inverse agonists and neutral antagonists as cognitive enhancers in neurodegenerative and psychiatric disorders is certainly of utmost interest. (C) 2017 Elsevier Masson SAS. All rights reserved.
• US8680089B2
  申请人：——

  公开号：US8680089B2

  公开（公告）日：2014-03-25
• [EN] FUSED PYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRIDINE CONDENSÉS
  申请人：KBP BIOMEDICAL CO LTD

  公开号：WO2011085643A1

  公开（公告）日：2011-07-21

  Fused pyridine derivatives shown as the general formula (I), and their pharmaceutically acceptable salts, stereoisomers or solvates thereof are disclosed, which belong to the technical field of medicines. The R1, R2, R3, Q, X and Y substituents in formula (I) are defined as in the description. Also disclosed are the preparation methods, pharmaceutical compositions and uses of the compounds in the manufacture of the medicine for the treatment and/or prevention of noninsulin-dependent diabetes, hyperglycemia, hyperlipidemia and insulin resistance.