(R)-desazadesmethyldesferrithiocin sodium salt | 133817-91-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-desazadesmethyldesferrithiocin sodium salt
• 英文别名: sodium;(4R)-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-thiazole-4-carboxylate
• CAS: 133817-91-1
• 化学式: C₁₀H₈NO₃S*Na
• 分子量: 245.234
• InChiKey: QSQWRFSVAHFSHI-FJXQXJEOSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.29
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-desazadesmethyldesferrithiocin sodium salt 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 (3S,4S)-3-[[[(4R)-2-(2-hydroxyphenyl)-2-thiazolin-4-yl]carbonyl]amino]-4-methyl-2-oxoazetidine-1-sulfonic acid tetrabutylammonium salt
  参考文献：
  名称：

  Antimicrobial effects of novel siderophores linked to β-lactam antibiotics

  摘要：

  As a strategy to increase the penetration of antibiotic drugs through the outer membrane of Gram-negative pathogens, facilitated transport through siderophore receptors has been frequently exploited. Hydroxamic acids, catechols, or very close isosteres of catechols, which are mimics of naturally occurring siderophores, have been used successfully as covalently linked escorting moieties, but a much wider diversity of iron binding motifs exists. This observation, coupled to the relative lack of specificity of siderophore receptors, prompted us to initiate a program to identify novel, noncatechol siderophoric structures. We screened over 300 compounds for their ability to (1) support growth in low iron medium of a Pseudomonas aeruginosa siderophore biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore-antibiotic conjugate for siderophore receptor access. From these assays we identified a set of small molecules that fulfilled one or both of these criteria. We then synthesized these compounds with functional groups suitable for attachment to both monobactam and cephalosporin core structures. Siderophore-P-lactam conjugates then were tested against a panel of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of the resultant chimeric compounds had antimicrobial activity approaching that of ceftazidime, and most compounds demonstrated very potent activity against their cellular targets, only a single compound was obtained that had enhanced, siderophore-mediated antibacterial activity. Results with tonB mutants frequently showed increased rather than decreased susceptibilities, suggesting that multiple factors influenced the intracellular concentration of the drugs. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00261-8
• 作为产物：
  描述：

  邻羟基苯甲腈 、 L-半胱氨酸盐酸盐无水物 在 碳酸氢钠 、 哌啶 作用下， 以 乙醇 为溶剂， 反应 12.5h， 以67%的产率得到(R)-desazadesmethyldesferrithiocin sodium salt
  参考文献：
  名称：

  To Log or Not to Log: Bootstrap as an Alternative to the Parametric Estimation of Moderation Effects in the Presence of Skewed Dependent Variables

  摘要：

  当观察到与参数假设存在明显偏差时，通常会应用传统数据转换方法，很少考虑实质性理论影响。其中一种转换涉及使用呈正偏的因变量的对数。在蒙特卡洛模拟中，通过使用简单的百分位自举程序在原始的正偏数据中估计，模拟回归程序严重降低了真实调节效应的估计。在原始的正偏数据中，通过简单的百分位自举程序估计的调节效应大小估计明显更好地估计了真实的潜在调节效应（即增加了2.6到534倍）。在原始的正偏数据中，使用简单自举程序得出的关于真实调节效应存在与否的结论不受参数假设违反的影响。相比之下，对对数转换的因变量进行的模拟回归分析严重增加了二型错误。对应用心理学和管理研究的影响进行了讨论。

  DOI：

  10.1177/109442810032002

文献信息

• BERGERON, RAYMOND J.;WIEGAND, JAN;DIONIS, JOHN B.;EGLI-KARMAKKA, MAJIA;FR+, J. MED. CHEM., 34,(1991) N, C. 2072-2078
  作者：BERGERON, RAYMOND J.、WIEGAND, JAN、DIONIS, JOHN B.、EGLI-KARMAKKA, MAJIA、FR+

  DOI：——

  日期：——
• To Log or Not to Log: Bootstrap as an Alternative to the Parametric Estimation of Moderation Effects in the Presence of Skewed Dependent Variables
  作者：Craig J. Russell、Michelle A. Dean

  DOI：10.1177/109442810032002

  日期：2000.4

  When gross deviations from parametric assumptions are observed, conventional data transformations are often applied with little regard for substantive theoretical implications. One such transformation involves using the logarithm of positively skewed dependent variables. Log transformations were shown to severely decrease estimates of true moderator effects using moderated regression procedures in a Monte Carlo simulation. Estimates of moderator effect sizes were substantially better estimates of the true latent moderator effect (i.e., larger by a multiple of 2.6 to 534) when estimated using a simple percentile bootstrap procedure in the original, positively skewed data. Conclusions with regard to the presence or absence of a true moderator effect using a simple bootstrap procedure were unaffected by the violation of parametric assumptions in the original, positively skewed data. In contrast, moderated regression analysis performed on a log-transformed dependent variable severely increased Type-II error. Implications are drawn for applied psychological and management research.

  当观察到与参数假设存在明显偏差时，通常会应用传统数据转换方法，很少考虑实质性理论影响。其中一种转换涉及使用呈正偏的因变量的对数。在蒙特卡洛模拟中，通过使用简单的百分位自举程序在原始的正偏数据中估计，模拟回归程序严重降低了真实调节效应的估计。在原始的正偏数据中，通过简单的百分位自举程序估计的调节效应大小估计明显更好地估计了真实的潜在调节效应（即增加了2.6到534倍）。在原始的正偏数据中，使用简单自举程序得出的关于真实调节效应存在与否的结论不受参数假设违反的影响。相比之下，对对数转换的因变量进行的模拟回归分析严重增加了二型错误。对应用心理学和管理研究的影响进行了讨论。
• Antimicrobial effects of novel siderophores linked to β-lactam antibiotics
  作者：T Kline、M Fromhold、T.E McKennon、S Cai、J Treiberg、N Ihle、D Sherman、W Schwan、M.J Hickey、P Warrener、P.R Witte、L.L Brody、L Goltry、L.M Barker、S.U Anderson、S.K Tanaka、R.M Shawar、L.Y Nguyen、M Langhorne、A Bigelow、L Embuscado、E Naeemi

  DOI：10.1016/s0968-0896(99)00261-8

  日期：2000.1

  As a strategy to increase the penetration of antibiotic drugs through the outer membrane of Gram-negative pathogens, facilitated transport through siderophore receptors has been frequently exploited. Hydroxamic acids, catechols, or very close isosteres of catechols, which are mimics of naturally occurring siderophores, have been used successfully as covalently linked escorting moieties, but a much wider diversity of iron binding motifs exists. This observation, coupled to the relative lack of specificity of siderophore receptors, prompted us to initiate a program to identify novel, noncatechol siderophoric structures. We screened over 300 compounds for their ability to (1) support growth in low iron medium of a Pseudomonas aeruginosa siderophore biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore-antibiotic conjugate for siderophore receptor access. From these assays we identified a set of small molecules that fulfilled one or both of these criteria. We then synthesized these compounds with functional groups suitable for attachment to both monobactam and cephalosporin core structures. Siderophore-P-lactam conjugates then were tested against a panel of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of the resultant chimeric compounds had antimicrobial activity approaching that of ceftazidime, and most compounds demonstrated very potent activity against their cellular targets, only a single compound was obtained that had enhanced, siderophore-mediated antibacterial activity. Results with tonB mutants frequently showed increased rather than decreased susceptibilities, suggesting that multiple factors influenced the intracellular concentration of the drugs. (C) 2000 Elsevier Science Ltd. All rights reserved.