5-bromopyridine-2-carbothioamide

• 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
• 英文名称: 5-bromopyridine-2-carbothioamide
• 化学式: C₆H₅BrN₂S
• 分子量: 217.089
• InChiKey: SXLVGDLUSGTMND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  10
• 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：
  71
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromopyridine-2-carbothioamide 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 、 二碳酸二叔丁酯 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.5h， 生成 1-methyl-N-((6-(4-methylthiazol-2-yl)pyridin-3-yl)methyl)-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Optimization of Novel 1-Methyl-1H-Pyrazole-5-carboxamides Leads to High Potency Larval Development Inhibitors of the Barber’s Pole Worm

  摘要：

  A phenotypic screen of a diverse library of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of a 1-methyl-1H-pyrazole-5-carboxamide derivative with an IC50 of 0.29 mu M. Medicinal chemistry optimization targeted modifications on the left-hand side (LHS), middle section, and right-hand side (RHS) of the scaffold in order to elucidate the structure-activity relationship (SAR). Strong SAR allowed for the iterative and directed assembly of a focus set of 64 analogues, from which compound 60 was identified as the most potent compound, inhibiting the development of the fourth larval (L4) stage with an IC50 of 0.01 mu M. In contrast, only 18% inhibition of the mammary epithelial cell line MCF10A viability was observed, even at concentrations as high as 50 mu M.

  DOI：

  10.1021/acs.jmedchem.8b01544
• 作为产物：
  描述：

  5-溴-2-氰基吡啶 在 tetraphosphorus decasulfide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以72%的产率得到5-bromopyridine-2-carbothioamide
  参考文献：
  名称：

  小分子作为长波长荧光团：推挽取代4-烷氧基-1,3-噻唑

  摘要：

  专用于瓦尔德马亚当教授在他的80之际个生日 抽象的 已经合成了一系列供体-π-受体（D-π-A）取代的4-羟基噻唑。给电子基团（4-甲氧基苯基和4-二甲基氨基苯基）安装在噻唑的5-位；将噻吩/吡啶桥联的受体（甲酰基及其Knoevenagel缩合产物）置于2位。通过UV / Vis和荧光光谱研究了D-π-A特性对光物理性质和电子结构的影响。 已经合成了一系列供体-π-受体（D-π-A）取代的4-羟基噻唑。给电子基团（4-甲氧基苯基和4-二甲基氨基苯基）安装在噻唑的5-位；将噻吩/吡啶桥联的受体（甲酰基及其Knoevenagel缩合产物）置于2位。通过UV / Vis和荧光光谱研究了D-π-A特性对光物理性质和电子结构的影响。

  DOI：

  10.1055/s-0036-1588581

文献信息

• Structure-kinetics relationships of Capadenoson derivatives as adenosine A 1 receptor agonists
  作者：Julien Louvel、Dong Guo、Marjolein Soethoudt、Tamara A.M. Mocking、Eelke B. Lenselink、Thea Mulder-Krieger、Laura H. Heitman、Adriaan P. IJzerman

  DOI：10.1016/j.ejmech.2015.07.023

  日期：2015.8

  We report the synthesis and biological evaluation of new derivatives of Capadenoson, a former drug candidate that was previously advanced to phase Ha clinical trials. 19 of the 20 ligands show an affinity below 100 nM at the human adenosine A(1) receptor (hA(1)AR) and display a wide range of residence times at this target (from approx. 5 min (compound 10) up to 132 min (compound 5)). Structure-affinity and structure-kinetics relationships were established, and computational studies of a homology model of the hA(1)AR revealed crucial interactions for both the affinity and dissociation kinetics of this family of ligands. These results were also combined with global metrics (Ligand Efficiency, cLogP), showing the importance of binding kinetics as an additional way to better select a drug candidate amongst seemingly similar leads. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Optimization of Novel 1-Methyl-1<i>H</i>-Pyrazole-5-carboxamides Leads to High Potency Larval Development Inhibitors of the Barber’s Pole Worm
  作者：Thuy G. Le、Abhijit Kundu、Atanu Ghoshal、Nghi H. Nguyen、Sarah Preston、Yaqing Jiao、Banfeng Ruan、Lian Xue、Fei Huang、Jennifer Keiser、Andreas Hofmann、Bill C. H. Chang、Jose Garcia-Bustos、Abdul Jabbar、Timothy N. C. Wells、Michael J. Palmer、Robin B. Gasser、Jonathan B. Baell

  DOI：10.1021/acs.jmedchem.8b01544

  日期：2018.12.13

  A phenotypic screen of a diverse library of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of a 1-methyl-1H-pyrazole-5-carboxamide derivative with an IC50 of 0.29 mu M. Medicinal chemistry optimization targeted modifications on the left-hand side (LHS), middle section, and right-hand side (RHS) of the scaffold in order to elucidate the structure-activity relationship (SAR). Strong SAR allowed for the iterative and directed assembly of a focus set of 64 analogues, from which compound 60 was identified as the most potent compound, inhibiting the development of the fourth larval (L4) stage with an IC50 of 0.01 mu M. In contrast, only 18% inhibition of the mammary epithelial cell line MCF10A viability was observed, even at concentrations as high as 50 mu M.
• Small Molecules as Long-Wavelength Fluorophores: Push-Pull Substituted 4-Alkoxy-1,3-thiazoles
  作者：Rainer Beckert、Stefanie Habenicht、Philip Rohland、Jeaninne Reichel、Tarita Biver、Pierpaolo Minei、Dörthe Jakobi、Andrea Pucci、Dieter Weiß、Helmar Görls

  DOI：10.1055/s-0036-1588581

  日期：2018.1

  investigated by means of UV/Vis and fluorescence spectroscopy. A series of donor-π-acceptor (D-π-A) substituted 4-hydroxythiazoles have been synthesized. Electron-donating groups (4-methoxyphenyl and 4-dimethylaminophenyl) were installed in the 5-position of the thiazole; thiophene/pyridine-bridged acceptors (formyl groups and their Knoevenagel condensation products) were placed in the 2-position. The influence

  专用于瓦尔德马亚当教授在他的80之际个生日 抽象的 已经合成了一系列供体-π-受体（D-π-A）取代的4-羟基噻唑。给电子基团（4-甲氧基苯基和4-二甲基氨基苯基）安装在噻唑的5-位；将噻吩/吡啶桥联的受体（甲酰基及其Knoevenagel缩合产物）置于2位。通过UV / Vis和荧光光谱研究了D-π-A特性对光物理性质和电子结构的影响。 已经合成了一系列供体-π-受体（D-π-A）取代的4-羟基噻唑。给电子基团（4-甲氧基苯基和4-二甲基氨基苯基）安装在噻唑的5-位；将噻吩/吡啶桥联的受体（甲酰基及其Knoevenagel缩合产物）置于2位。通过UV / Vis和荧光光谱研究了D-π-A特性对光物理性质和电子结构的影响。