4-(chloromethyl)-2-(3-chlorophenyl)thiazole | 97992-66-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(chloromethyl)-2-(3-chlorophenyl)thiazole
• 英文别名: 4-chloromethyl-2-(3-chloro-phenyl)-thiazole；4-(Chloromethyl)-2-(3-chlorophenyl)-1,3-thiazole
• CAS: 97992-66-0
• 化学式: C₁₀H₇Cl₂NS
• mdl: MFCD11177609
• 分子量: 244.144
• InChiKey: JUBWAXBCONSZDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  14
• 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-chlorophenyl)thiazole 在 manganese(IV) oxide 、 硫酸 、 水 作用下， 以 氯仿 为溶剂， 反应 12.0h， 生成 2-(3-氯苯基)-1,3-噻唑-4-甲醛
  参考文献：
  名称：

  多官能化 4-（2-芳基噻唑-4-基）-4H-色烯的合成和体外细胞毒性

  摘要：

  新系列的 4-芳基-4H-色烯在4-位带有2-芳基噻唑-4-基部分被制备为潜在的细胞毒性剂。使用MTT比色法研究合成的4-芳基-4H-色烯与众所周知的抗癌药物依托泊苷的体外细胞毒活性。其中，2-(2-氯苯基)噻唑-4-基类似物4b对鼻咽表皮样癌KB、髓母细胞瘤DAOY和星形细胞瘤1321N1显示出最有效的活性，以及​​带有2-(4-氯苯基)噻唑的化合物4d色烯环4-位的4-基部分对乳腺癌细胞MCF-7、肺癌细胞A549和结肠腺癌细胞SW480表现出最好的抑制活性，IC50值小于5 μM。

  DOI：

  10.1002/ardp.200900198
• 作为产物：
  描述：

  3-氯苯腈 在 吡啶 、 硫化氢 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 4-(chloromethyl)-2-(3-chlorophenyl)thiazole
  参考文献：
  名称：

  多官能化 4-（2-芳基噻唑-4-基）-4H-色烯的合成和体外细胞毒性

  摘要：

  新系列的 4-芳基-4H-色烯在4-位带有2-芳基噻唑-4-基部分被制备为潜在的细胞毒性剂。使用MTT比色法研究合成的4-芳基-4H-色烯与众所周知的抗癌药物依托泊苷的体外细胞毒活性。其中，2-(2-氯苯基)噻唑-4-基类似物4b对鼻咽表皮样癌KB、髓母细胞瘤DAOY和星形细胞瘤1321N1显示出最有效的活性，以及​​带有2-(4-氯苯基)噻唑的化合物4d色烯环4-位的4-基部分对乳腺癌细胞MCF-7、肺癌细胞A549和结肠腺癌细胞SW480表现出最好的抑制活性，IC50值小于5 μM。

  DOI：

  10.1002/ardp.200900198

文献信息

• Synthesis and structure–activity relationships of 2-aryl-4-oxazolylmethoxy benzylglycines and 2-aryl-4-thiazolylmethoxy benzylglycines as novel, potent PPARα selective activators- PPARα and PPARγ selectivity modulation
  作者：Xiang-Yang Ye、Stephanie Chen、Hao Zhang、Kenneth T. Locke、Kevin O’Malley、Litao Zhang、Raijit Srivastava、Bowman Miao、Daniel Meyers、Hossain Monshizadegan、Debra Search、Denise Grimm、Rongan Zhang、Jonathan Lippy、Celeste Twamley、Jodi K. Muckelbauer、Chiehying Chang、Yongmi An、Vinayak Hosagrahara、Lisa Zhang、T.-J. Yang、Ranjan Mukherjee、Peter T.W. Cheng、Joseph A. Tino

  DOI：10.1016/j.bmcl.2010.03.019

  日期：2010.5

  The synthesis and follow-up SAR studies of our development candidate 1 by incorporating 2-aryl-4-oxazolylmethoxy and 2-aryl-4-thiazolylmethoxy moieties into the oxybenzylglycine framework of the PPAR alpha/gamma dual agonist muraglitazar is described. SAR studies indicate that different substituents on the aryloxazole/thiazole moieties as well as the choice of carbamate substituent on the glycine moiety can significantly modulate the selectivity of PPAR alpha versus PPAR gamma. Potent, highly selective PPAR alpha activators 2a and 2l, as well as PPAR alpha activators with significant PPAR gamma activity, such as 2s, were identified. The in vivo pharmacology of these compounds in preclinical animal models as well as their ADME profiles are discussed. (C) 2010 Elsevier Ltd. All rights reserved.
• 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.