(3R)-6-amino-8-cyclopropyl-7-(naphthalen-1-yl)methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester | 916314-58-4

• 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: (3R)-6-amino-8-cyclopropyl-7-(naphthalen-1-yl)methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester
• 英文别名: (3R)-6-Amino-8-cyclopropyl-7-naphthalen-1-ylmethyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester；methyl (3R)-6-amino-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylate
• CAS: 916314-58-4
• 化学式: C₂₃H₂₂N₂O₃S
• 分子量: 406.505
• InChiKey: RQCPSVSZQVAZSP-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 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：
  97.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R)-6-amino-8-cyclopropyl-7-(naphthalen-1-yl)methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以100%的产率得到lithium (3R)-6-amino-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：

  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：

  5-(1-hydroxy-2-(naphthalen-1-yl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 在 氧气 、 溶剂黄146 、 三氟乙酸 、 锌 、 sodium nitrite 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 35.04h， 生成 (3R)-6-amino-8-cyclopropyl-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：

  Thiazolino 2-Pyridone Amide Inhibitors ofChlamydia trachomatisInfectivity

  摘要：

  The bacterial pathogen Chlamydia trachomatis is a global health burden currently treated with broad-spectrum antibiotics which disrupt commensal bacteria. We recently identified a compound through phenotypic screening that blocked infectivity of this intracellular pathogen without host cell toxicity (compound 1, KSK 120). Herein, we present the optimization of 1 to a class of thiazolino 2-pyridone amides that are highly efficacious (EC50 <= 100 nM) in attenuating infectivity across multiple serovars of C. trachomatis without host cell toxicity. The lead compound 21a exhibits reduced lipophilicity versus 1 and did not affect the growth or viability of representative commensal flora at 50 mu M. In microscopy studies, a highly active fluorescent analogue 37 localized inside the parasitiphorous inclusion, indicative of a specific targeting of bacterial components. In summary, we present a class of small molecules to enable the development of specific treatments for C. trachomatis.

  DOI：

  10.1021/acs.jmedchem.5b01759

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。
• 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。
• New Compounds
  申请人：Almqvist Fredrik

  公开号：US20080139607A1

  公开（公告）日：2008-06-12

  The present invention relates to new compounds of formula (I), (II), or (III) wherein R 1 , R 2 , R 3 , R 4 , R 5 and W are as defined herein, and methods of using the compounds to inhibit PAI-1 and to treat PAI-1 related disorders.

  本发明涉及式(I)、(II)或(III)的新化合物，其中R1、R2、R3、R4、R5和W的定义如本文所述，并且使用这些化合物抑制PAI-1和治疗PAI-1相关疾病的方法。
• WO2008/54290
  申请人：——

  公开号：——

  公开（公告）日：——