3,5-bis(2-propylpyridin-4-yl)-1,2,4-thiadiazole

• 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: 3,5-bis(2-propylpyridin-4-yl)-1,2,4-thiadiazole
• 英文别名: 3,5-Bis(2-propylpyridin-4-yl)-1,2,4-thiadiazole
• 化学式: C₁₈H₂₀N₄S
• 分子量: 324.45
• InChiKey: NCXVZXGLJPQPBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  丙硫异烟胺 在 碘 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以69.9%的产率得到3,5-bis(2-propylpyridin-4-yl)-1,2,4-thiadiazole
  参考文献：
  名称：

  Diarylthiazole: An Antimycobacterial Scaffold Potentially Targeting PrrB-PrrA Two-Component System

  摘要：

  Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE)>0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.

  DOI：

  10.1021/jm500833f

文献信息

• Diarylthiazole: An Antimycobacterial Scaffold Potentially Targeting PrrB-PrrA Two-Component System
  作者：Eknath Bellale、Maruti Naik、Varun VB、Anisha Ambady、Ashwini Narayan、Sudha Ravishankar、Vasanthi Ramachandran、Parvinder Kaur、Robert McLaughlin、James Whiteaker、Sapna Morayya、Supreeth Guptha、Sreevalli Sharma、Anandkumar Raichurkar、Disha Awasthy、Vijayshree Achar、Prakash Vachaspati、Balachandra Bandodkar、Manoranjan Panda、Monalisa Chatterji

  DOI：10.1021/jm500833f

  日期：2014.8.14

  Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE)>0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.