(2R)-2-[[4-[4-(4-methoxyphenoxy)-1-piperidyl]phenoxy]methyl]-2-methyl-6-nitro-3H-imidazo[2,1-b]oxazole

• 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: (2R)-2-[[4-[4-(4-methoxyphenoxy)-1-piperidyl]phenoxy]methyl]-2-methyl-6-nitro-3H-imidazo[2,1-b]oxazole
• 英文别名: (2R)-2-[[4-[4-(4-methoxyphenoxy)piperidin-1-yl]phenoxy]methyl]-2-methyl-6-nitro-3H-imidazo[2,1-b][1,3]oxazole
• 化学式: C₂₅H₂₈N₄O₆
• 分子量: 480.521
• InChiKey: HFGFXADTXQORAA-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-对溴苯氧基四氢吡喃 在 palladium diacetate 、 4-甲基苯磺酸吡啶 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 乙醇 、 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 26.5h， 生成 (2R)-2-[[4-[4-(4-methoxyphenoxy)-1-piperidyl]phenoxy]methyl]-2-methyl-6-nitro-3H-imidazo[2,1-b]oxazole
  参考文献：
  名称：

  Synthesis and Antituberculosis Activity of a Novel Series of Optically Active 6-Nitro-2,3-dihydroimidazo[2,1-b]oxazoles

  摘要：

  In an effort to develop potent new antituberculosis agents that would be effective against both drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis, we prepared a novel series of optically active 6-nitro-2,3-dihydroimidazo[2,1-b]oxazoles substituted at the 2-position with various phenoxymethyl groups and a methyl group and investigated the in vitro and in vivo activity of these compounds. Several of these derivatives showed potent in vitro and in vivo activity, and compound 19 (OPC-67683) in particular displayed excellent in vitro activity against both drug-susceptible and drug-resistant strains of M. tuberculosis H(37)Rv (MIC = 0.006 mu g/mL) and dose-dependent and significant in vivo efficacy at lower oral doses than rifampicin in mouse models infected with M. tuberculosis Kurono. The synthesis and structure-activity relationships of these new compounds are presented.

  DOI：

  10.1021/jm060957y

文献信息

• COMBINATION THERAPY TO TREAT MYCOBACTERIUM DISEASES
  申请人：Locher Christopher Phillip

  公开号：US20140045791A1

  公开（公告）日：2014-02-13

  The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein X and R are as defined herein. The compounds of formula (I) are useful as gyrase and/or topoisomerase IV inhibitors for treating bacterial infections. The compounds of formula (I) either possess a broad range of anti-bacterial activity and advantageous toxicological properties or are prodrugs of compounds having said activity.

  本发明涉及式(I)化合物或其药学上可接受的盐，其中X和R的定义如本文所述。式(I)化合物可用作抑制DNA旋转酶和/或拓扑异构酶IV的抑制剂，用于治疗细菌感染。式(I)化合物具有广泛的抗菌活性和优越的毒理学特性，或者是具有该活性的前药。
• US9572809B2
  申请人：——

  公开号：US9572809B2

  公开（公告）日：2017-02-21
• Synthesis and Antituberculosis Activity of a Novel Series of Optically Active 6-Nitro-2,3-dihydroimidazo[2,1-<i>b</i>]oxazoles
  作者：Hirofumi Sasaki、Yoshikazu Haraguchi、Motohiro Itotani、Hideaki Kuroda、Hiroyuki Hashizume、Tatsuo Tomishige、Masanori Kawasaki、Makoto Matsumoto、Makoto Komatsu、Hidetsugu Tsubouchi

  DOI：10.1021/jm060957y

  日期：2006.12.1

  In an effort to develop potent new antituberculosis agents that would be effective against both drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis, we prepared a novel series of optically active 6-nitro-2,3-dihydroimidazo[2,1-b]oxazoles substituted at the 2-position with various phenoxymethyl groups and a methyl group and investigated the in vitro and in vivo activity of these compounds. Several of these derivatives showed potent in vitro and in vivo activity, and compound 19 (OPC-67683) in particular displayed excellent in vitro activity against both drug-susceptible and drug-resistant strains of M. tuberculosis H(37)Rv (MIC = 0.006 mu g/mL) and dose-dependent and significant in vivo efficacy at lower oral doses than rifampicin in mouse models infected with M. tuberculosis Kurono. The synthesis and structure-activity relationships of these new compounds are presented.