(3R)-8-cyclopropyl-7-(naphthalen-1-yl)methyl-6-nitro-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester | 916314-56-2

• 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)-8-cyclopropyl-7-(naphthalen-1-yl)methyl-6-nitro-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester
• 英文别名: (3R)-8-Cyclopropyl-7-naphthalen-1-ylmethyl-6-nitro-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester；methyl (3R)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-6-nitro-5-oxo-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylate
• CAS: 916314-56-2
• 化学式: C₂₃H₂₀N₂O₅S
• 分子量: 436.488
• InChiKey: IJVMLTBVLQWCRG-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 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：
  118
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R)-8-cyclopropyl-7-(naphthalen-1-yl)methyl-6-nitro-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester 在 乙酸酐 、 溶剂黄146 、 锌 作用下， 反应 10.0h， 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：

  5-(1-hydroxy-2-(naphthalen-1-yl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 在 氧气 、 三氟乙酸 、 sodium nitrite 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 15.04h， 生成 (3R)-8-cyclopropyl-7-(naphthalen-1-yl)methyl-6-nitro-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

• 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：——
• Thiazolino 2-Pyridone Amide Inhibitors of<i>Chlamydia trachomatis</i>Infectivity
  作者：James A. D. Good、Jim Silver、Carlos Núñez-Otero、Wael Bahnan、K. Syam Krishnan、Olli Salin、Patrik Engström、Richard Svensson、Per Artursson、Åsa Gylfe、Sven Bergström、Fredrik Almqvist

  DOI：10.1021/acs.jmedchem.5b01759

  日期：2016.3.10

  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.
• Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2-pyridones—Targeting virulence of uropathogenic E. coli
  作者：Veronica Åberg、Magnus Sellstedt、Mattias Hedenström、Jerome S. Pinkner、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1016/j.bmc.2006.07.017

  日期：2006.11

  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.