(R)-(4-chlorophenyl)(3-((1-(3-(1-hydroxyoctyl)benzyl)piperidin-4-yl)methoxy)phenyl)methanone O-methyloxime | 1372526-45-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R)-(4-chlorophenyl)(3-((1-(3-(1-hydroxyoctyl)benzyl)piperidin-4-yl)methoxy)phenyl)methanone O-methyloxime
• 英文别名: (1R)-1-[3-[[4-[[3-[C-(4-chlorophenyl)-N-methoxycarbonimidoyl]phenoxy]methyl]piperidin-1-yl]methyl]phenyl]octan-1-ol
• CAS: 1372526-45-8
• 化学式: C₃₅H₄₅ClN₂O₃
• 分子量: 577.207
• InChiKey: VAMSAIRJSAEDPG-UUWRZZSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  54.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯-N-甲氧基-N-甲基乙酰胺 在 吡啶 、 偶氮二甲酸二异丙酯 、 氢溴酸 、 异丙基氯化镁 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三苯基膦 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 61.5h， 生成 (R)-(4-chlorophenyl)(3-((1-(3-(1-hydroxyoctyl)benzyl)piperidin-4-yl)methoxy)phenyl)methanone O-methyloxime
  参考文献：
  名称：

  Discovery of Selective Menaquinone Biosynthesis Inhibitors against Mycobacterium tuberculosis

  摘要：

  Aurachin RE (1) is a strong antibiotic that was recently found to possess 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) and bacterial electron transport inhibitory activities. Aurachin RE is the only molecule in a series of aurachin natural products that has the chiral center in the alkyl side chain at C9'-position. To identify selective MenA inhibitors against Mycobacterium tuberculosis, a series of chiral molecules were designed based on the structures of previously identified MenA inhibitors and 1. The synthesized molecules were evaluated in in vitro assays, including MenA enzyme and bacterial growth inhibitory assays. We could identify novel MenA inhibitors that showed significant increase in potency of killing nonreplicating M. tuberculosis in the low oxygen recovery assay (LORA) without inhibiting other Gram-positive bacterial growth even at high concentrations. The MenA inhibitors reported here are useful new pharmacophores for the development of selective antimycobacterial agents with strong activity against nonreplicating M. tuberculosis.

  DOI：

  10.1021/jm201608g

文献信息

• Discovery of Selective Menaquinone Biosynthesis Inhibitors against Mycobacterium tuberculosis
  作者：Joy Debnath、Shajila Siricilla、Bajoie Wan、Dean C. Crick、Anne J. Lenaerts、Scott G. Franzblau、Michio Kurosu

  DOI：10.1021/jm201608g

  日期：2012.4.26

  Aurachin RE (1) is a strong antibiotic that was recently found to possess 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) and bacterial electron transport inhibitory activities. Aurachin RE is the only molecule in a series of aurachin natural products that has the chiral center in the alkyl side chain at C9'-position. To identify selective MenA inhibitors against Mycobacterium tuberculosis, a series of chiral molecules were designed based on the structures of previously identified MenA inhibitors and 1. The synthesized molecules were evaluated in in vitro assays, including MenA enzyme and bacterial growth inhibitory assays. We could identify novel MenA inhibitors that showed significant increase in potency of killing nonreplicating M. tuberculosis in the low oxygen recovery assay (LORA) without inhibiting other Gram-positive bacterial growth even at high concentrations. The MenA inhibitors reported here are useful new pharmacophores for the development of selective antimycobacterial agents with strong activity against nonreplicating M. tuberculosis.