(R)-N-{3-[methoxy(methyl)amino]-3-oxopropyl}-2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamide | 1351758-31-0

• 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)-N-{3-[methoxy(methyl)amino]-3-oxopropyl}-2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamide
• 英文别名: (4R)-N-[3-[methoxy(methyl)amino]-3-oxopropyl]-2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamide
• CAS: 1351758-31-0
• 化学式: C₁₄H₂₆N₂O₅
• 分子量: 302.371
• InChiKey: RTBQTOZZLWIUHN-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N-{3-[methoxy(methyl)amino]-3-oxopropyl}-2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamide 在 氯化铋 、 magnesium 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 16.0h， 生成 (R)-2,4-dihydroxy-3,3-dimethyl-N-[3-oxo-4-(4-trifluoromethoxyphenyl)butyl]butanamide
  参考文献：
  名称：

  VANIN-1 INHIBITOR

  摘要：

  A Vanin-1 inhibitor includes as an active ingredient a pantotheine ketone derivative represented by the following Formula (I), wherein X, Y, Y′, Z, and Z′ are independently selected from a hydrogen atom, a fluorine group, and a substituent substituted with a fluorine group, and at least one of X, Y, Y′, Z, or Z′ is a fluorine group or a substituent substituted with a fluorine group.

  公开号：

  US20240277639A1
• 作为产物：
  描述：

  calcium (R)-pantothenate 在 盐酸 、 4-二甲氨基吡啶 、 硫酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 35.0h， 生成 (R)-N-{3-[methoxy(methyl)amino]-3-oxopropyl}-2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamide
  参考文献：
  名称：

  VANIN-1 INHIBITOR

  摘要：

  A Vanin-1 inhibitor includes as an active ingredient a pantotheine ketone derivative represented by the following Formula (I), wherein X, Y, Y′, Z, and Z′ are independently selected from a hydrogen atom, a fluorine group, and a substituent substituted with a fluorine group, and at least one of X, Y, Y′, Z, or Z′ is a fluorine group or a substituent substituted with a fluorine group.

  公开号：

  US20240277639A1

文献信息

• Combination of Pantothenamides with Vanin Inhibitors as a Novel Antibiotic Strategy against Gram-Positive Bacteria
  作者：Patrick A. M. Jansen、Pedro H. H. Hermkens、Patrick L. J. M. Zeeuwen、Peter N. M. Botman、Richard H. Blaauw、Peter Burghout、Peter M. van Galen、Johan W. Mouton、Floris P. J. T. Rutjes、Joost Schalkwijk

  DOI：10.1128/aac.00603-13

  日期：2013.10

  The emergence of resistance against current antibiotics calls for the development of new compounds to treat infectious diseases. Synthetic pantothenamides are pantothenate analogs that possess broad-spectrum antibacterial activity in vitro in minimal media. Pantothenamides were shown to be substrates of the bacterial coenzyme A (CoA) biosynthetic pathway, causing cellular CoA depletion and interference with fatty acid synthesis. In spite of their potential use and selectivity for bacterial metabolic routes, these compounds have never made it to the clinic. In the present study, we show that pantothenamides are not active as antibiotics in the presence of serum, and we found that they were hydrolyzed by ubiquitous pantetheinases of the vanin family. To address this further, we synthesized a series of pantetheinase inhibitors based on a pantothenate scaffold that inhibited serum pantetheinase activity in the nanomolar range. Mass spectrometric analysis showed that addition of these pantetheinase inhibitors prevented hydrolysis of pantothenamides by serum. We found that combinations of these novel pantetheinase inhibitors and prototypic pantothenamides like N5-Pan and N7-Pan exerted antimicrobial activity in vitro , particularly against Gram-positive bacteria ( Staphylococcus aureus , Staphylococcus epidermidis , Streptococcus pneumoniae , and Streptococcus pyogenes ) even in the presence of serum. These results indicate that pantothenamides, when protected against degradation by host pantetheinases, are potentially useful antimicrobial agents.

  摘要 随着现有抗生素耐药性的出现，需要开发新的化合物来治疗传染性疾病。合成泛酸酰胺是泛酸盐类似物，具有广谱抗菌活性 体外 在最小培养基中具有广谱抗菌活性。研究表明，泛酰苯胺是细菌辅酶 A（CoA）生物合成途径的底物，可导致细胞 CoA 枯竭并干扰脂肪酸合成。尽管这些化合物在细菌代谢途径中具有潜在的用途和选择性，但却从未应用于临床。在本研究中，我们发现泛硫氨酸在血清存在的情况下并不具有抗生素活性，而且它们会被无处不在的香兰素家族泛硫氨酸酶水解。为了进一步解决这个问题，我们合成了一系列基于泛酸盐支架的泛酪素酶抑制剂，它们能在纳摩尔范围内抑制血清泛酪素酶的活性。质谱分析表明，加入这些泛硫氨酸酶抑制剂可防止血清水解泛酸。我们发现，这些新型泛影葡胺酶抑制剂与 N5-Pan 和 N7-Pan 等原型泛影葡胺的组合具有抗菌活性 在体外 尤其是对革兰氏阳性菌（金黄色葡萄球菌、葡萄球菌 金黄色葡萄球菌 , 表皮葡萄球菌 , 肺炎链球菌 和 化脓性链球菌 ），即使在有血清存在的情况下也是如此。这些结果表明，泛硫酰胺在受到宿主泛硫酶降解保护的情况下，有可能成为有用的抗菌剂。
• Design, synthesis, and evaluation of new vanin-1 inhibitors based on RR6
  作者：Hiroki Yoneyama、Keiko Hosohata、Denan Jin、Iroha Yoshida、Miyui Toyoda、Ikuko Kitamura、Shinji Takai、Yoshihide Usami

  DOI：10.1016/j.bmc.2022.116791

  日期：2022.7

  Fourteen novel vanin-1 inhibitors coded OMP-# were designed from RR6 and successfully synthesized by a nucleophilic addition–elimination reaction of the pantetheinic acid-derived Weinreb amide as a key step under Barbier conditions. The synthesized OMP compounds exhibited inhibitory activity against human serum vanin-1 in vitro. Among the synthesized compounds, OMP-7, which possesses a trifluoromethoxy

  14 种编码 OMP-# 的新型 vanin-1 抑制剂是从 RR6 设计的，并通过泛酸衍生的 Weinreb 酰胺的亲核加成 - 消除反应成功合成，这是 Barbier 条件下的关键步骤。合成的 OMP 化合物在体外表现出对人血清 vanin-1 的抑制活性。在合成的化合物中，在苯环对位具有三氟甲氧基的OMP-7表现出最强的活性，约为母化合物RR6的20倍。进一步对 OMP-7 进行体内使用正常仓鼠进行检测。观察到比 RR6 对血清和肾 vanin-1 更有效的活性。注射血清 vanin-1 后活性持续 4 小时，注射肾 vanin-1 后活性持续 1 小时，而 RR6 没有显示出所需的活性。