| 1160960-61-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• CAS: 1160960-61-1
• 化学式: C₅₁H₄₈N₁₂O₁₁S₆
• 分子量: 1197.41
• InChiKey: GLHVEBDISISGNA-AJXKHVGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.63
• 重原子数：
  80.0
• 可旋转键数：
  10.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  317.79
• 氢给体数：
  6.0
• 氢受体数：
  24.0

反应信息

• 作为反应物：
  描述：

  在 sodium azide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 15.83h， 生成 2-[(18S,25S,35S)-8-(4-amino-1,3-thiazol-2-yl)-35-[(S)-hydroxy(phenyl)methyl]-28-(methoxymethyl)-21-methyl-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-18-yl]-N-methylacetamide;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  4-Aminothiazolyl Analogues of GE2270 A: Antibacterial Lead Finding

  摘要：

  4-Aminothiazolyl analogues of the antibacterial natural product GE2270 A (1) were designed, synthesized, and evaluated for Gram positive bacteria growth inhibition. The aminothiazole-based chemical template was evaluated for chemical stability, and its decomposition revealed a novel, structurally simplified, des-thiazole analogue of 1. Subsequent stabilization of the 4-aminothiazolyl functional motif was achieved and initial structure activity relationships defined.

  DOI：

  10.1021/jm101602q
• 作为产物：
  描述：

  GE2270 A 在 甲酸 、 水 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  4-Aminothiazolyl Analogues of GE2270 A: Antibacterial Lead Finding

  摘要：

  4-Aminothiazolyl analogues of the antibacterial natural product GE2270 A (1) were designed, synthesized, and evaluated for Gram positive bacteria growth inhibition. The aminothiazole-based chemical template was evaluated for chemical stability, and its decomposition revealed a novel, structurally simplified, des-thiazole analogue of 1. Subsequent stabilization of the 4-aminothiazolyl functional motif was achieved and initial structure activity relationships defined.

  DOI：

  10.1021/jm101602q

文献信息

• Discovery of LFF571: An Investigational Agent for <i>Clostridium difficile</i> Infection
  作者：Matthew J. LaMarche、Jennifer A. Leeds、Adam Amaral、Jason T. Brewer、Simon M. Bushell、Gejing Deng、Janetta M. Dewhurst、Jian Ding、JoAnne Dzink-Fox、Gabriel Gamber、Akash Jain、Kwangho Lee、Lac Lee、Troy Lister、David McKenney、Steve Mullin、Colin Osborne、Deborah Palestrant、Michael A. Patane、Elin M. Rann、Meena Sachdeva、Jian Shao、Stacey Tiamfook、Anna Trzasko、Lewis Whitehead、Aregahegn Yifru、Donghui Yu、Wanlin Yan、Qingming Zhu

  DOI：10.1021/jm201685h

  日期：2012.3.8

  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.