2-[(2-chlorophenyl)amino]-1,3-thiazole-4-carboxylic acid | 165682-81-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[(2-chlorophenyl)amino]-1,3-thiazole-4-carboxylic acid
• 英文别名: 2-(2-Chloro-phenylamino)-thiazole-4-carboxylic acid；2-(2-chloroanilino)-1,3-thiazole-4-carboxylic acid
• CAS: 165682-81-5
• 化学式: C₁₀H₇ClN₂O₂S
• 分子量: 254.697
• InChiKey: OMOCHAFOYVWXNL-UHFFFAOYSA-N

物化性质

• 沸点：
  453.0±51.0 °C(Predicted)
• 密度：
  1.565±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  90.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(2-chlorophenyl)amino]-1,3-thiazole-4-carboxylic acid 、 4-甲基哌啶 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N-(2-chlorophenyl)-4-[(4-methyl-1-piperidinyl)carbonyl]-1,3-thiazol-2-amine
  参考文献：
  名称：

  The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore

  摘要：

  Lead optimization of piperidine amide HTS hits, based on an anilino-thiazole core, led to the identification of analogs which displayed low nanomolar blocking activity at the canonical transient receptor channels 3 and 6 (TRPC3 & 6) based on FLIPR (carbachol stimulated) and electrophysiology (OAG stimulated) assays. In addition, the anilino-thiazole amides displayed good selectivity over other TRP channels (TRPA1, TRPV1, and TRPV4), as well as against cardiac ion channels (CaV1.2, hERG, and NaV1.5). The high oxidation potential of the aliphatic piperidine and aniline groups, as well as the lability of the thiazole amide group contributed to the high clearance observed for this class of compounds. Conversion of an isoquinoline amide to a naphthyridine amide markedly reduced clearance for the bicyclic piperidines, and improved oral bioavailability for this compound series, however TRPC3 and TRPC6 blocking activity was reduced substantially. Although the most potent anilino-thiazole amides ultimately lacked oral exposure in rodents and were not suitable for chronic dosing, analogs such as 14-19, 22, and 23 are potentially valuable in vitro tool compounds for investigating the role of TRPC3 and TRPC6 in cardiovascular disease. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.06.047
• 作为产物：
  描述：

  邻氯苯基硫脲 在 吡啶 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 生成 2-[(2-chlorophenyl)amino]-1,3-thiazole-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and evaluation of thiazole carboxamides as vanilloid receptor 1 (TRPV1) antagonists

  摘要：

  A thiazole derivative, 2-(2,6-dichlorobenzyl)-N-(4-isopropylphenyl) thiazole-4-carboxamide (1), was identified as a TRPV1 antagonist. We synthesized various thiazole analogs and evaluated them for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. The IC50 values of the most potent antagonists were ca. 0.050 mu M in these assays. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.100

文献信息

• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2012037351A1

  公开（公告）日：2012-03-22

  Compounds, pharmaceutical compositions containing them, and their use treatment of conditions mediated by the TRPC3 and/or TRPC6 ion channels.

  化合物，含有它们的制药组合物，以及它们用于治疗由TRPC3和/或TRPC6离子通道介导的疾病的用途。
• [EN] FUNGICIDE AMINOTHIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'AMINOTHIAZOLE FONGICIDES
  申请人：BAYER CROPSCIENCE SA

  公开号：WO2010012793A1

  公开（公告）日：2010-02-04

  The present invention relates to aminothiazole derivatives of formula (I), their process of preparation, preparation intermediate compounds, their use as fungicide, acaricide or insecticide active agents, particularly in the form of fungicide, acaricide or insecticide compositions and methods for the control of phytopathogenic fungi, notably of plants, using these compounds or compositions. Formula (I) wherein R1 to R5 represent various substituents as described in the description.

  本发明涉及公式（I）的氨基噻唑衍生物，其制备方法，制备中间化合物，它们作为杀真菌剂、杀螨剂或杀虫剂活性剂的用途，特别是作为杀真菌剂、杀螨剂或杀虫剂组合物的形式，以及利用这些化合物或组合物控制植物病原真菌，尤其是植物的方法。其中，公式（I）中的R1至R5代表描述中的各种取代基。
• Synthesis and evaluation of thiazole carboxamides as vanilloid receptor 1 (TRPV1) antagonists
  作者：Ning Xi、Yunxin Bo、Elizabeth M. Doherty、Christopher Fotsch、Narender R. Gavva、Nianhe Han、Randall W. Hungate、Lana Klionsky、Qingyian Liu、Rami Tamir、Shimin Xu、James J.S. Treanor、Mark H. Norman

  DOI：10.1016/j.bmcl.2005.08.100

  日期：2005.12

  A thiazole derivative, 2-(2,6-dichlorobenzyl)-N-(4-isopropylphenyl) thiazole-4-carboxamide (1), was identified as a TRPV1 antagonist. We synthesized various thiazole analogs and evaluated them for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. The IC50 values of the most potent antagonists were ca. 0.050 mu M in these assays. (c) 2005 Elsevier Ltd. All rights reserved.
• The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore
  作者：David G. Washburn、Dennis A. Holt、Jason Dodson、Jeff J. McAtee、Lamont R. Terrell、Linda Barton、Sharada Manns、Anna Waszkiewicz、Christina Pritchard、Dan J. Gillie、Dwight M. Morrow、Elizabeth A. Davenport、Irina M. Lozinskaya、Jeffrey Guss、Jonathan B. Basilla、Lorena Kallal Negron、Michael Klein、Robert N. Willette、Rusty E. Fries、Timothy C. Jensen、Xiaoping Xu、Christine G. Schnackenberg、Joseph P. Marino

  DOI：10.1016/j.bmcl.2013.06.047

  日期：2013.9

  Lead optimization of piperidine amide HTS hits, based on an anilino-thiazole core, led to the identification of analogs which displayed low nanomolar blocking activity at the canonical transient receptor channels 3 and 6 (TRPC3 & 6) based on FLIPR (carbachol stimulated) and electrophysiology (OAG stimulated) assays. In addition, the anilino-thiazole amides displayed good selectivity over other TRP channels (TRPA1, TRPV1, and TRPV4), as well as against cardiac ion channels (CaV1.2, hERG, and NaV1.5). The high oxidation potential of the aliphatic piperidine and aniline groups, as well as the lability of the thiazole amide group contributed to the high clearance observed for this class of compounds. Conversion of an isoquinoline amide to a naphthyridine amide markedly reduced clearance for the bicyclic piperidines, and improved oral bioavailability for this compound series, however TRPC3 and TRPC6 blocking activity was reduced substantially. Although the most potent anilino-thiazole amides ultimately lacked oral exposure in rodents and were not suitable for chronic dosing, analogs such as 14-19, 22, and 23 are potentially valuable in vitro tool compounds for investigating the role of TRPC3 and TRPC6 in cardiovascular disease. Published by Elsevier Ltd.