4-(chloromethyl)-2-(3,4-dichlorophenyl)thiazole | 89873-42-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(chloromethyl)-2-(3,4-dichlorophenyl)thiazole
• 英文别名: chloromethyl-2-(3,4-dichloro-phenyl)-thiazole；2-(3,4-dichlorophenyl)-4-chloromethylthiazole；4-(Chloromethyl)-2-(3,4-dichlorophenyl)-1,3-thiazole
• CAS: 89873-42-7
• 化学式: C₁₀H₆Cl₃NS
• 分子量: 278.589
• InChiKey: ITDVLYBNNYRMRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(chloromethyl)-2-(3,4-dichlorophenyl)thiazole 、 6-amino-4-(4-methoxyphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以86%的产率得到2-amino-6-{[2-(3,4-dichlorophenyl)thiazol-4-yl]methylthio}-4-(4-methoxyphenyl)pyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  Structure-kinetics relationships of Capadenoson derivatives as adenosine A 1 receptor agonists

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2015.07.023
• 作为产物：
  描述：

  3,4-二氯苯腈 在 吡啶 、 ammonium sulfide 、 三乙胺 作用下， 以 水 、 甲苯 为溶剂， 生成 4-(chloromethyl)-2-(3,4-dichlorophenyl)thiazole
  参考文献：
  名称：

  Agonists for the Adenosine A₁ Receptor with Tunable Residence Time. A Case for Nonribose 4-Amino-6-aryl-5-cyano-2-thiopyrimidines

  摘要：

  We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A(1) receptor (hA(1)AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.

  DOI：

  10.1021/jm401643m
• 作为试剂：
  描述：

  3,4-二氯硫代苯胺 以 4-(chloromethyl)-2-(3,4-dichlorophenyl)thiazole 为溶剂， 生成 5-[2-(3,4-dimethylphenyl)thiazol-4-yl]-4-hydroxy-3(2H)-isothiazolone-1,1-dioxide
  参考文献：
  名称：

  4-Hydroxy-5-substituted-3(2H)-isothiazolone-1,1-dioxide derivatives

  摘要：

  该公式为：##STR1## 其中X和Y独立地选自氢、卤素和C.sub.1-6烷基的组，但取代苯基部分的2号和6号位置不能被C.sub.3-6烷基取代；或其药学上可接受的盐；用于治疗尿路感染，特别是肾钙草酸盐结石。

  公开号：

  US04431652A1

文献信息

• 5-Aryl-4-hydroxy-3(2H)-isothiazolone 1,1-dioxide derivatives. Synthesis and carbon-13 NMR characterization
  作者：C. S. Rooney、D. W. Cochran、C. Ziegler、E. J. Cragoe、H. W. R. Williams

  DOI：10.1021/jo00186a028

  日期：1984.6
• ROONEY, C. S.;COCHRAN, D. W.;ZIEGLER, C.;CRAGOE, E. J. ,, JR;WILLIAMS, H.+, J. ORG. CHEM., 1984, 49, N 12, 2212-2217
  作者：ROONEY, C. S.、COCHRAN, D. W.、ZIEGLER, C.、CRAGOE, E. J. ,, JR、WILLIAMS, H.+

  DOI：——

  日期：——
• US4431652A
  申请人：——

  公开号：US4431652A

  公开（公告）日：1984-02-14
• Agonists for the Adenosine A₁ Receptor with Tunable Residence Time. A Case for Nonribose 4-Amino-6-aryl-5-cyano-2-thiopyrimidines
  作者：Julien Louvel、Dong Guo、Marta Agliardi、Tamara A. M. Mocking、Roland Kars、Tan Phát Pham、Lizi Xia、Henk de Vries、Johannes Brussee、Laura H. Heitman、Adriaan P. IJzerman

  DOI：10.1021/jm401643m

  日期：2014.4.24

  We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A(1) receptor (hA(1)AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.
• 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.