methyl (3R)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-5H-[1,3 ]thiazolo[3,2-a]pyridine-3-carboxylate | 478297-75-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (3R)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-5H-[1,3 ]thiazolo[3,2-a]pyridine-3-carboxylate
• 英文别名: methyl (3R)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylate
• CAS: 478297-75-5
• 化学式: C₂₃H₂₁NO₃S
• 分子量: 391.491
• InChiKey: ROPJKDUJKDZZFL-IBGZPJMESA-N

物化性质

• 沸点：
  643.1±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  71.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (3R)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-5H-[1,3 ]thiazolo[3,2-a]pyridine-3-carboxylate 在 氧气 、 乙酸酐 、 溶剂黄146 、 三氟乙酸 、 锌 、 sodium nitrite 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 (3R)-8-cyclopropyl-6-formylamino-7-(naphthalen-1-yl)methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2-pyridones—Targeting virulence of uropathogenic E. coli

  摘要：

  Substituted bicyclic 2-pyridones, termed pilicides, are dipeptide mimetics that prevent pilus assembly in uropathogenic Escherichia coli. Here, we apply rational design to produce four classes of extended peptidomimetics based on two bioactive 2-pyridones. The key intermediate in the synthesis was an amino-functionalised 2-pyridone scaffold, which could be obtained via a mild and selective nitration and subsequent reduction. Procedures were then developed to further derivatize this amino-substituted core and a total of 24 extended peptidomimetics were synthesised and evaluated for chaperone affinity and in vivo antivirulence activity in P pili producing E coli. Enhanced affinities for the target protein were observed within the generated set of compounds, while the ability to prevent pilus assembly in vivo was significantly decreased compared to the parent lead compounds. The results suggest that the limited in vivo potencies of the analogues are either uptake/distribution related or due to loss in binding specificity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.07.017
• 作为产物：
  描述：

  1-萘乙酸 在 盐酸 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 0.8h， 生成 methyl (3R)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-5H-[1,3 ]thiazolo[3,2-a]pyridine-3-carboxylate
  参考文献：
  名称：

  Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Aβ-peptide aggregation inhibitors

  摘要：

  开发了一种无试剂的微波辅助去羧化程序，用于羧酸功能化的双环2-吡啶酮。该新方法基于在N-甲基吡咯烷酮（NMP）中以220°C加热600秒，证明实用且非常高效，产生的去羧化2-吡啶酮几乎定量。去羧化产品和羧酸甲酯及羧酸形式的中间体2-吡啶酮被筛选以研究其对Aβ肽聚集的影响。在本研究中描述的21种2-吡啶酮中，有两种抑制了阿尔茨海默病Aβ(1–40)肽的淀粉样蛋白形成。即使在2-吡啶酮与单体Aβ肽的比率为4:1时，仍观察到了这种效果。

  DOI：

  10.1039/b503294f

文献信息

• Synthesis of a Novel Tricyclic Peptidomimetic Scaffold
  作者：Magnus Sellstedt、Fredrik Almqvist

  DOI：10.1021/ol801506y

  日期：2008.9.18

  An efficient method to synthesize a novel rigid tricyclic peptidomimetic scaffold through ring-closure of amino-functionalized bicyclic 2-pyridones has been discovered. The scaffold can function as a peptide backbone mimetic (highlighted) with two substituents independently variable to fine-tune biological response. Halogenation of the pyrazolo ring followed by Suzuki couplings made it possible to

  已发现通过氨基官能化的双环2-吡啶酮的闭环合成新型刚性三环拟肽骨架的有效方法。支架可以用作具有两个独立取代基的肽骨架模拟物（突出显示），以微调生物学反应。吡唑并环的卤化和随后的铃木偶联使在合成路线的后期引入具有可变电子性质的取代基成为可能，这在文库合成中是优选的。
• Functionalization of bicyclic 2-pyridones targeting pilus biogenesis in uropathogenic Escherichia coli
  作者：Nils Pemberton、Jerome S. Pinkner、Jennifer M. Jones、Lotta Jakobsson、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1016/j.tetlet.2007.04.142

  日期：2007.6

  Substituted bicyclic 2-pyridones, termed pilicides, prevent pilus assembly in uropathogenic Escherichia coli. Based on the bioactive methyl ester protected 2-pyridone 4, further functionalization at C-6 has yielded a set of new compounds, which have been evaluated for their ability to inhibit pilus formation in uropathogenic E. coli. The key intermediate in the synthesis was formylated 2-pyridone 5

  取代的双环2-吡啶酮（称为杀菌剂）可防止尿路致病性大肠杆菌中的菌毛组装。基于具有生物活性的甲基酯保护的2-吡啶酮4，在C-6处的进一步官能化产生了一组新化合物，已对其在尿毒症大肠杆菌中抑制菌毛形成的能力进行了评估。合成中的关键中间体是甲酰化的2-吡啶酮5，可以通过Vilsmeier反应获得。这种多用途的中间体通过还原胺化转化为仲胺和叔胺，也可以通过简单的化学转化将其转化为其他有趣的官能团。
• Synthesis of Multiring Fused 2-Pyridones via a Nitrene Insertion Reaction: Fluorescent Modulators of α-Synuclein Amyloid Formation
  作者：Pardeep Singh、Erik Chorell、K. Syam Krishnan、Tomas Kindahl、Jörgen Åden、Pernilla Wittung-Stafshede、Fredrik Almqvist

  DOI：10.1021/acs.orglett.5b03190

  日期：2015.12.18

  catalyst-free, microwave-assisted, intramolecular C–H amination reaction is reported. All the synthesized polyheterocycles were evaluated for their fluorescent properties and effect on α-synuclein amyloid formation.

  据报道，一种高效，直接的方法可通过无催化剂，微波辅助的分子内C–H胺化反应合成噻唑-2-吡啶酮嵌入的拟肽多杂环化合物。评价所有合成的多杂环化合物的荧光性质以及对α-突触核蛋白淀粉样蛋白形成的影响。
• [EN] RING-FUSED THIAZOLINO 2-PYRIDONES, METHODS FOR PREPARATION THEREOF AND THEIR USE IN THE TREATMENT AND/OR PREVENTION OF TUBERCULOSIS<br/>[FR] THIAZOLINO 2-PYRIDONES À CYCLES FUSIONNÉS, LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION DANS LE TRAITEMENT ET/OU LA PRÉVENTION DE LA TUBERCULOSE
  申请人：QURETECH BIO AB

  公开号：WO2017175182A1

  公开（公告）日：2017-10-12

  The present disclosure provides a combination comprising: (i) a drug against tuberculosis, or a pharmaceutically acceptable salt thereof, and (ii) a compound of Formula (II), or a pharmaceutically acceptable combination thereof. The combination may be used in the treatment and/or prevention of tuberculosis.

  本公开提供了一种组合物，包括：（i）用于治疗结核病的药物或其药用盐，以及（ii）式（II）的化合物，或其药用可接受的组合物。该组合物可用于治疗和/或预防结核病。
• Diverse Functionalization of Thiazolo Ring-Fused 2-Pyridones
  作者：Erik Chorell、Pralay Das、Fredrik Almqvist

  DOI：10.1021/jo0704053

  日期：2007.6.1

  thiazolo part of this system can be substituted either via conjugate additions, resulting in trans selectivity, or via microwave-assisted Heck couplings that result in unsaturated aryl-substituted analogues. The scaffold can also be lithiated followed by the addition of various electrophiles, which increases the diversification potential substantially, as exemplified with the introduction of halogens, alkyl

  噻唑环稠合的2-吡啶酮已被证明是开发生物活性化合物的非常令人感兴趣的支架。当今有许多方法可用于在杂环的2-吡啶酮部分中引入各种取代基。本文中，我们公开了如何在噻唑环中引入各种不同的取代基，并且还可以改变取代基的空间排列。关键中间体是氧化骨架9为此，描述了一种有效的合成方法。该体系的噻唑部分可通过共轭加成反应以产生反式选择性，或通过微波辅助的Heck偶联来取代，从而产生不饱和的芳基取代的类似物。支架也可以被锂化，然后添加各种亲电试剂，这大大增加了多样化的潜力，例如引入卤素，烷基，酰基和酰胺取代基。