| 1361395-26-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• CAS: 1361395-26-7
• 化学式: C₆₁H₆₅N₁₃O₁₃S₆
• 分子量: 1380.66
• InChiKey: CQWUADNLYZMGLB-WOBXYZTASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  93.0
• 可旋转键数：
  19.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  344.17
• 氢给体数：
  5.0
• 氢受体数：
  26.0

反应信息

• 作为反应物：
  描述：

  在 水 、 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以48%的产率得到5-[3-carboxypropyl-[2-[(18S,25S,35S)-35-[(S)-hydroxy(phenyl)methyl]-28-(methoxymethyl)-21-methyl-18-[2-(methylamino)-2-oxoethyl]-16,23,30,33-tetraoxo-25-propan-2-yl-3,13,20,27,37-pentathia-7,17,24,31,34,39,40,41,42,43-decazaheptacyclo[34.2.1.12,5.112,15.119,22.126,29.06,11]tritetraconta-1(38),2(43),4,6(11),7,9,12(42),14,19(41),21,26(40),28,36(39)-tridecaen-8-yl]-1,3-thiazol-4-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Discovery of LFF571: An Investigational Agent for Clostridium difficile Infection

  摘要：

  Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection.

  DOI：

  10.1021/jm201685h
• 作为产物：
  描述：

  戊二酸单乙酯酰氯 、 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Discovery of LFF571: An Investigational Agent for Clostridium difficile Infection

  摘要：

  Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection.

  DOI：

  10.1021/jm201685h