1-羟基-6-硫代-1,6-二氢吡啶-2-羧酸 | 131490-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 1-羟基-6-硫代-1,6-二氢吡啶-2-羧酸
• 英文名称: 1-hydroxy-6-thioxo-1,6-dihydropyridine-2-carboxylic acid
• 英文别名: 1-hydroxypyridine-2(1H)-thione-6-carboxylic acid；1-hydroxypyridine-2-thione-6-carboxylic acid；2-mercaptopyridine-6-carboxylic acid-1-oxide；1-Hydroxy-6-sulfanylidene-1,6-dihydropyridine-2-carboxylic acid；1-hydroxy-6-sulfanylidenepyridine-2-carboxylic acid
• CAS: 131490-25-0
• 化学式: C₆H₅NO₃S
• mdl: MFCD20646150
• 分子量: 171.177
• InChiKey: BNYCWOPXGQKREA-UHFFFAOYSA-N

物化性质

• 沸点：
  360.8±52.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-羟基-6-硫代-1,6-二氢吡啶-2-羧酸 在 lithium hydroxide monohydrate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 13.17h， 生成 (R)-2-(1-hydroxy-6-thioxo-1,6-dihydropyridine-2-carboxamido)propanoic acid
  参考文献：
  名称：

  Cell permeable vanX inhibitors as vancomycin re-sensitizing agents

  摘要：

  VanX is an induced zinc metallo D-Ala-D-Ala dipeptidase involved in the viable remodeling of bacterial cell wall that is essential for the development of VREF. Here we report two cyclic thiohydroxamic acid-based peptide analogs that were designed, synthesized and investigated as vancomycin re-sensitizing agents. These compounds exhibit low micromolar inhibitory activity against vanX, with low cytotoxicity and were shown to increase vancomycin sensitivity against VREF. The improved pharmacological properties of these novel inhibitors over previous transition state mimics should provide an enhanced platform for designing potent vanX inhibitors for overcoming vancomycin resistance. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.097
• 作为产物：
  描述：

  6-溴-2-吡啶羧酸 在 sodium hydrogen sulfide 、 sodiumsulfide nonahydrate 、 双氧水 作用下， 以 水 、 三氟乙酸 为溶剂， 反应 36.0h， 生成 1-羟基-6-硫代-1,6-二氢吡啶-2-羧酸
  参考文献：
  名称：

  Cell permeable vanX inhibitors as vancomycin re-sensitizing agents

  摘要：

  VanX is an induced zinc metallo D-Ala-D-Ala dipeptidase involved in the viable remodeling of bacterial cell wall that is essential for the development of VREF. Here we report two cyclic thiohydroxamic acid-based peptide analogs that were designed, synthesized and investigated as vancomycin re-sensitizing agents. These compounds exhibit low micromolar inhibitory activity against vanX, with low cytotoxicity and were shown to increase vancomycin sensitivity against VREF. The improved pharmacological properties of these novel inhibitors over previous transition state mimics should provide an enhanced platform for designing potent vanX inhibitors for overcoming vancomycin resistance. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.097

文献信息

• [EN] NOVEL COMPOUNDS AND METHODS OF USING THEM<br/>[FR] COMPOSÉS NOVATEURS ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：SYNDAX PHARMACEUTICALS INC

  公开号：WO2009015203A1

  公开（公告）日：2009-01-29

  Described herein are novel HDAC modulators, formulations containing them and methods of using them. In some embodiments, the HDAC modulators possess specific stereo chemistry. In other embodiments, the compounds described herein are used in the treatment or prevention of histone deacetylase mediated disorders.

  本文描述了新型HDAC调节剂，含有它们的配方以及使用它们的方法。在某些实施例中，HDAC调节剂具有特定的立体化学结构。在其他实施例中，本文描述的化合物用于治疗或预防组蛋白去乙酰化酶介导的疾病。
• Small-Molecule-Mediated Cleavage of RNA in Living Cells
  作者：Lirui Guan、Matthew D. Disney

  DOI：10.1002/anie.201206888

  日期：2013.1.28

  Killing the message: An approach to direct the cleavage of RNA targets with small molecules in living cells is described (see scheme). A bifunctional small molecule (purple) that recognizes a specific three nucleotide repeat sequence and cleaves that sequence in response to light was shown to be effective at degrading the myotonic dystrophy type 1 (DM1) extended repeat RNAs, thereby affecting biological

  Killing the message：描述了一种在活细胞中用小分子直接切割 RNA 靶标的方法（参见方案）。一种双功能小分子（紫色）识别特定的三核苷酸重复序列并响应光切割该序列被证明可有效降解 1 型肌强直性营养不良 (DM1) 扩展重复 RNA，从而影响生物学功能。
• THERAPEUTIC METHODS AND COMBINATIONS
  申请人：Sham Yuk Yin

  公开号：US20180369217A1

  公开（公告）日：2018-12-27

  Combinations comprising substituted 1-hydroxypyridine-2(1H)-thiones or a pharmaceutically acceptable salt thereof and an antibacterial agent are disclosed. Also disclosed are therapeutic methods comprising the administration of a substituted 1-hydroxypyridine-2(1H)-thione or a pharmaceutically acceptable salt thereof and an antibacterial agent.

  本发明涉及含有取代的1-羟基吡啶-2（1H）-硫酮或其药学上可接受的盐和抗菌剂的组合物。还公开了包括给予取代的1-羟基吡啶-2（1H）-硫酮或其药学上可接受的盐和抗菌剂的治疗方法。
• Novel Compounds and Methods of Using Them
  申请人：Keana John F.W.

  公开号：US20100298270A1

  公开（公告）日：2010-11-25

  Described herein are novel HDAC modulators, formulations containing them and methods of using them. In some embodiments, the HDAC modulators possess specific stereo chemistry. In other embodiments, the compounds described herein are used in the treatment or prevention of histone deacetylase mediated disorders.

  本文描述了一种新型的HDAC调节剂，包含它们的制剂和使用它们的方法。在某些实施例中，HDAC调节剂具有特定的立体化学。在其他实施例中，本文所描述的化合物被用于治疗或预防组蛋白去乙酰化酶介导的疾病。
• Thioamide Hydroxypyrothiones Supersede Amide Hydroxypyrothiones in Potency against Anthrax Lethal Factor
  作者：Arpita Agrawal、César Augusto F. de Oliveira、Yuhui Cheng、Jennifer A. Jacobsen、J. Andrew McCammon、Seth M. Cohen

  DOI：10.1021/jm8013212

  日期：2009.2.26

  Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of anthrax. A structure-activity relationship (SAR) of potential lethal factor inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematically varied. It was found that hydroxypyrothione ZBGs generate more potent inhibitors than hydroxypyrone ZBGs. Furthermore, coupling the hydroxypyrothione to a backbone group via a thioamide bond improves potency when compared to an amide linker. QM/MM studies show that the thioamide bond in these inhibitors allows for the formation of two additional hydrogen bonds with the protein active site. In both types of hydroxypyrothione compounds, ligand efficiencies of 0.29-0.54 kcal mol(-1) per heavy atom were achieved. The results highlight the need for a better understanding to optimize the interplay between the ZBG, linker, and backbone to get improved LFi.