4'-methyl-N²-(p-tolyl)-[4,5'-bithiazole]-2,2'-diamine | 315704-87-1

• 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'-methyl-N²-(p-tolyl)-[4,5'-bithiazole]-2,2'-diamine
• 英文别名: 4-Methyl-5-[2-(4-methylanilino)-1,3-thiazol-4-yl]-1,3-thiazol-2-amine
• CAS: 315704-87-1
• 化学式: C₁₄H₁₄N₄S₂
• 分子量: 302.424
• InChiKey: AVCOHPBLQGEPBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4'-methyl-N²-(p-tolyl)-[4,5'-bithiazole]-2,2'-diamine 、 丁酰氯 在 三乙胺 作用下， 以 氯仿 为溶剂， 生成
  参考文献：
  名称：

  4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing

  摘要：

  The synthesis and Delta F508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human Delta F508-CFTR. These structure-activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.037
• 作为产物：
  描述：

  5-乙酰基-2-氨基-4-甲基噻唑 在 氢溴酸 、 溴 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 2.0h， 生成 4'-methyl-N²-(p-tolyl)-[4,5'-bithiazole]-2,2'-diamine
  参考文献：
  名称：

  Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery

  摘要：

  Tuberculosis remains one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extremely drug-resistant strains is a significant reason for concern. This makes the discovery of novel antitubercular agents a cogent priority. We have previously addressed this need by reporting a series of substituted 2-aminothiazoles capable to inhibit the growth of actively replicating, nonreplicating persistent, and resistant Mycobacterium tuberculosis strains. Clues from the structureactivity relationships lining up the antitubercular activity were exploited for the rational design of improved analogues. Two compounds, namely N-phenyl-5-(2-(p-tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 7a and N-(pyridin-2-yl)-5-(2-(p-tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 8a, were found to show high inhibitory activity toward susceptible M. tuberculosis strains, with an MIC90 of 0.1250.25 mu g/mL (0.330.66 mu M) and 0.060.125 mu g/mL (0.160.32 mu M), respectively. Moreover, they maintained good activity also toward resistant strains, and they were selective over other bacterial species and eukaryotic cells, metabolically stable, and apparently not susceptible to the action of efflux pumps.

  DOI：

  10.1021/acs.jmedchem.7b00793

文献信息

• 4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing
  作者：Choong Leol Yoo、Gui Jun Yu、Baoxue Yang、Lori I. Robins、A.S. Verkman、Mark J. Kurth

  DOI：10.1016/j.bmcl.2008.03.037

  日期：2008.4

  The synthesis and Delta F508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human Delta F508-CFTR. These structure-activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies. (c) 2008 Elsevier Ltd. All rights reserved.
• Substituted <i>N</i>-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery
  作者：Elisa Azzali、Diana Machado、Amit Kaushik、Federica Vacondio、Sara Flisi、Clotilde Silvia Cabassi、Gyanu Lamichhane、Miguel Viveiros、Gabriele Costantino、Marco Pieroni

  DOI：10.1021/acs.jmedchem.7b00793

  日期：2017.8.24

  Tuberculosis remains one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extremely drug-resistant strains is a significant reason for concern. This makes the discovery of novel antitubercular agents a cogent priority. We have previously addressed this need by reporting a series of substituted 2-aminothiazoles capable to inhibit the growth of actively replicating, nonreplicating persistent, and resistant Mycobacterium tuberculosis strains. Clues from the structureactivity relationships lining up the antitubercular activity were exploited for the rational design of improved analogues. Two compounds, namely N-phenyl-5-(2-(p-tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 7a and N-(pyridin-2-yl)-5-(2-(p-tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 8a, were found to show high inhibitory activity toward susceptible M. tuberculosis strains, with an MIC90 of 0.1250.25 mu g/mL (0.330.66 mu M) and 0.060.125 mu g/mL (0.160.32 mu M), respectively. Moreover, they maintained good activity also toward resistant strains, and they were selective over other bacterial species and eukaryotic cells, metabolically stable, and apparently not susceptible to the action of efflux pumps.