2,4-dihydroxy-3,3-dimethyl-N-[2-(2-morpholin-4-yl-ethylcarbamoyl)ethyl]-butyramide

• 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: 2,4-dihydroxy-3,3-dimethyl-N-[2-(2-morpholin-4-yl-ethylcarbamoyl)ethyl]-butyramide
• 英文别名: N-(2-morpholin-4-yl-ethyl) homopantothenamide；(2R)-2,4-dihydroxy-3,3-dimethyl-N-[4-(2-morpholin-4-ylethylamino)-4-oxobutyl]butanamide
• 化学式: C₁₆H₃₁N₃O₅
• 分子量: 345.439
• InChiKey: AKCKYSWMJIOQCB-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  D-(-)-泛酰内酯 在 二苯基膦叠氮化物 、 二乙胺 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 2,4-dihydroxy-3,3-dimethyl-N-[2-(2-morpholin-4-yl-ethylcarbamoyl)ethyl]-butyramide
  参考文献：
  名称：

  Structure–activity relationships and enzyme inhibition of pantothenamide-type pantothenate kinase inhibitors

  摘要：

  A set of novel pantothenamide-type analogues of the known Staphylococcus aureus pantothenate kinase (SaPanK) inhibitors, N-pentyl, and N-heptylpantothenamide, was synthesized in three series. The first series of analogues (1-3) were designed as molecular probes of the PanK binding site to elucidate important structure-activity relationships (SAR). The second series of analogues (4-16) were designed using Structural information obtained from the Escherichia coli PanK (EcPanK) Structure by targeting the pantothenate binding site and the adjacent phenylalanine-lined lipophilic pocket. Insight into the antimicrobial effect of N-pen- tylpantothenamide (N5-Pan) through its Conversion to the antimetabolite ethyldethia-CoA and further incorporation into all inactive acyl carrier protein analogue drove the development of the third series of analogues (17-25) to enhance this effect using substrate-like substitutions. Each of the analogues was screened for enzyme inhibition activity against a panel of pantothenate kinases consisting of EcPanK, Aspergillus nidulans (AnPanK), SaPanK, and the murine isoform (MmPanK1 alpha). Series 1 demonstrated only modest inhibitory activity, but did reveal some important SAR findings including stereospecific binding. Series 2 demonstrated a much higher inhibition rate for the entire series and significant inhibition was seen with analogues containing alkyl substituents. Series 3 demonstrated the most preferential inhibition profile, with the highest inhibitory activity against the SaPanK greater selectivity. The overall activity data from these analogues Suggest a complex and non-enzynie specific SAR for pantotheriamide substrate/inhibitors of the different PanK enzymes. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.09.021

文献信息

• Development of a method for the parallel synthesis and purification of N-substituted pantothenamides, known inhibitors of coenzyme A biosynthesis and utilization
  作者：Marianne van Wyk、Erick Strauss

  DOI：10.1039/b811086g

  日期：——

  analogues which have been shown to act as inhibitors of coenzyme A biosynthesis and utilization, especially by blocking fatty acid metabolism through formation of inactive acyl carrier proteins. To fully explore the chemical diversity and inhibitory potential of these analogues we have developed a simple method for the parallel synthesis and purification of any number of pantothenamides from a single precursor

  N-取代的泛酰胺是一类泛酸类似物，已被证明可作为辅酶A生物合成和利用的抑制剂，特别是通过形成无活性的酰基载体蛋白来阻止脂肪酸代谢。为了全面探索这些类似物的化学多样性和抑制潜力，我们开发了一种简单的方法，用于从单个前体中并行合成和纯化任意数量的泛酰胺，随后评估了这些化合物的小文库作为细菌生长的抑制剂，以证明该方法的潜力和实用性。
• Structure–activity relationships and enzyme inhibition of pantothenamide-type pantothenate kinase inhibitors
  作者：Kristopher G. Virga、Yong-Mei Zhang、Roberta Leonardi、Robert A. Ivey、Kirk Hevener、Hee-Won Park、Suzanne Jackowski、Charles O. Rock、Richard E. Lee

  DOI：10.1016/j.bmc.2005.09.021

  日期：2006.2

  A set of novel pantothenamide-type analogues of the known Staphylococcus aureus pantothenate kinase (SaPanK) inhibitors, N-pentyl, and N-heptylpantothenamide, was synthesized in three series. The first series of analogues (1-3) were designed as molecular probes of the PanK binding site to elucidate important structure-activity relationships (SAR). The second series of analogues (4-16) were designed using Structural information obtained from the Escherichia coli PanK (EcPanK) Structure by targeting the pantothenate binding site and the adjacent phenylalanine-lined lipophilic pocket. Insight into the antimicrobial effect of N-pen- tylpantothenamide (N5-Pan) through its Conversion to the antimetabolite ethyldethia-CoA and further incorporation into all inactive acyl carrier protein analogue drove the development of the third series of analogues (17-25) to enhance this effect using substrate-like substitutions. Each of the analogues was screened for enzyme inhibition activity against a panel of pantothenate kinases consisting of EcPanK, Aspergillus nidulans (AnPanK), SaPanK, and the murine isoform (MmPanK1 alpha). Series 1 demonstrated only modest inhibitory activity, but did reveal some important SAR findings including stereospecific binding. Series 2 demonstrated a much higher inhibition rate for the entire series and significant inhibition was seen with analogues containing alkyl substituents. Series 3 demonstrated the most preferential inhibition profile, with the highest inhibitory activity against the SaPanK greater selectivity. The overall activity data from these analogues Suggest a complex and non-enzynie specific SAR for pantotheriamide substrate/inhibitors of the different PanK enzymes. (c) 2005 Elsevier Ltd. All rights reserved.