2-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one | 78831-01-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 2-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one
• 英文别名: 4,5-Dihydro-2-methyl-1,2,4-triazin-3(2H)-one；2-methyl-4,5-dihydro-1,2,4-triazin-3-one
• CAS: 78831-01-3
• 化学式: C₄H₇N₃O
• mdl: MFCD19223424
• 分子量: 113.119
• InChiKey: DENBSCKJHNQVFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one 在 盐酸 、 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以93%的产率得到2-methyl-1,2,4-triazinan-3-one
  参考文献：
  名称：

  Discovery of Efficacious Pseudomonas aeruginosa-Targeted Siderophore-Conjugated Monocarbams by Application of a Semi-mechanistic Pharmacokinetic/Pharmacodynamic Model

  摘要：

  To identify new agents for the treatment of multi-drug-resistant Pseudomonas aeruginosa, we focused on siderophore-conjugated monocarbams. This class of monocyclic beta-lactams are stable to metallo-beta-lactamases and have excellent P. aeruginosa activities due to their ability to exploit the iron uptake machinery of Gram-negative bacteria. Our medicinal chemistry plan focused on identifying a molecule with optimal potency and physical properties and activity for in vivo efficacy. Modifications to the monocarbam linker, siderophore, and oxime portion of the molecules were examined. Through these efforts, a series of pyrrolidinone-based monocarbams with good P. aeruginosa cellular activity (P. aeruginosa MIC90 = 2 mu g/mL), free fraction levels (>20% free), and hydrolytic stability (t(1/2) = 100 h) were identified. To differentiate the lead compounds and enable prioritization for in vivo studies, we applied a semi-mechanistic pharmacokinetic/pharmacodynamic model to enable prediction of in vivo efficacy from in vitro data.

  DOI：

  10.1021/jm501506f
• 作为产物：
  描述：

  2-methyl-5-methylthio-1,2,4-triazin-3(2H)-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以82.5%的产率得到2-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one
  参考文献：
  名称：

  Nakayama, Yoshinori; Sanemitsu, Yuzuru; Mizutani, Masato, Journal of Heterocyclic Chemistry, 1981, vol. 18, p. 631 - 632

  摘要：

  DOI：

文献信息

• NAKAYAMA YOSHINORI; SANEMITSU YUZURU; MIZUTANI MASATO; YOSHIOKA HIROSUKE, J. HETEROCYCL. CHEM., 1981, 18, NO 3, 631-632
  作者：NAKAYAMA YOSHINORI、 SANEMITSU YUZURU、 MIZUTANI MASATO、 YOSHIOKA HIROSUKE

  DOI：——

  日期：——
• Nakayama, Yoshinori; Sanemitsu, Yuzuru; Mizutani, Masato, Journal of Heterocyclic Chemistry, 1981, vol. 18, p. 631 - 632
  作者：Nakayama, Yoshinori、Sanemitsu, Yuzuru、Mizutani, Masato、Yoshioka, Hirosuke

  DOI：——

  日期：——
• Discovery of Efficacious <i>Pseudomonas aeruginosa</i>-Targeted Siderophore-Conjugated Monocarbams by Application of a Semi-mechanistic Pharmacokinetic/Pharmacodynamic Model
  作者：Kerry E. Murphy-Benenato、Pratik R. Bhagunde、April Chen、Hajnalka E. Davis、Thomas F. Durand-Réville、David E. Ehmann、Vincent Galullo、Jennifer J. Harris、Holia Hatoum-Mokdad、Haris Jahić、Aryun Kim、M. R. Manjunatha、Erika L. Manyak、John Mueller、Sara Patey、Olga Quiroga、Michael Rooney、Li Sha、Adam B. Shapiro、Mark Sylvester、Beesan Tan、Andy S. Tsai、Maria Uria-Nickelsen、Ye Wu、Mark Zambrowski、Shannon X. Zhao

  DOI：10.1021/jm501506f

  日期：2015.3.12

  To identify new agents for the treatment of multi-drug-resistant Pseudomonas aeruginosa, we focused on siderophore-conjugated monocarbams. This class of monocyclic beta-lactams are stable to metallo-beta-lactamases and have excellent P. aeruginosa activities due to their ability to exploit the iron uptake machinery of Gram-negative bacteria. Our medicinal chemistry plan focused on identifying a molecule with optimal potency and physical properties and activity for in vivo efficacy. Modifications to the monocarbam linker, siderophore, and oxime portion of the molecules were examined. Through these efforts, a series of pyrrolidinone-based monocarbams with good P. aeruginosa cellular activity (P. aeruginosa MIC90 = 2 mu g/mL), free fraction levels (>20% free), and hydrolytic stability (t(1/2) = 100 h) were identified. To differentiate the lead compounds and enable prioritization for in vivo studies, we applied a semi-mechanistic pharmacokinetic/pharmacodynamic model to enable prediction of in vivo efficacy from in vitro data.