(R)-2-氯-1-(2-甲基环氧乙烷-2-基甲基)-4-硝基咪唑 | 681490-93-7

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: (R)-2-氯-1-(2-甲基环氧乙烷-2-基甲基)-4-硝基咪唑
• 英文名称: (R)-2-chloro-1-((2-methyloxiran-2-yl)methyl)-4-nitro-1H-imidazole
• 英文别名: (R)-2-chloro-1-(2-methyl-2,3-epoxypropyl)-4-nitroimidazole；2-chloro-1-[[(2R)-2-methyloxiran-2-yl]methyl]-4-nitroimidazole；(R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole
• CAS: 681490-93-7
• 化学式: C₇H₈ClN₃O₃
• 分子量: 217.612
• InChiKey: SZMDGYNOADBVSR-SSDOTTSWSA-N

物化性质

• 熔点：
  72-73 °C
• 沸点：
  393.9±38.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P501,P273,P272,P260,P270,P202,P201,P271,P264,P280,P312,P337+P313,P305+P351+P338,P362+P364,P333+P313,P302+P352+P312,P304+P340+P312,P403+P233,P405
• 危险品运输编号：
  2811
• 危险性描述：
  H312,H303,H315,H319,H361,H372,H317,H351,H335,H336,H412

反应信息

• 作为反应物：
  描述：

  (R)-2-氯-1-(2-甲基环氧乙烷-2-基甲基)-4-硝基咪唑 在 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.33h， 生成 (R)-2-methyl-6-nitro-2-[4-(1-oxothiomorpholin-4-yl)phenoxymethyl]-2,3-dihydroimidazo[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
• 作为产物：
  描述：

  (R)-3-(2-chloro-4-nitro-1H-imidazol-1-yl)-2-hydroxy-2-methylpropylmethanesulfonate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以6.93 g的产率得到(R)-2-氯-1-(2-甲基环氧乙烷-2-基甲基)-4-硝基咪唑
  参考文献：
  名称：

  Synthesis of new generation triazolyl- and isoxazolyl-containing 6-nitro-2,3-dihydroimidazooxazoles as anti-TB agents: in vitro, structure–activity relationship, pharmacokinetics and in vivo evaluation

  摘要：

  有前途的硝基咪唑噁唑骨架提供了另一种新颖的三唑基含有的6-硝基-2,3-二氢咪唑噁唑作为抗结核病的先导化合物。

  DOI：

  10.1039/c5ob00054h

文献信息

• Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-<i>b</i>][1,3]oxazoles for Neglected Tropical Diseases: Structure–Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis
  作者：Andrew M. Thompson、Patrick D. O’Connor、Adrian Blaser、Vanessa Yardley、Louis Maes、Suman Gupta、Delphine Launay、Denis Martin、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、William A. Denny

  DOI：10.1021/acs.jmedchem.5b01699

  日期：2016.3.24

  linking oxygen for nitrogen (or piperazine), biaryl extension, and replacement of phenyl rings by pyridine. Several less lipophilic analogues displayed improved aqueous solubility, particularly at low pH, although stability toward liver microsomes was highly variable. Upon evaluation in a mouse model of acute Leishmania donovani infection, one phenylpyridine derivative (37) stood out, providing efficacy

  6-硝基-2,3-二氢咪唑[2,1- b最初在临床试验用药前驱体前药（PA-824）的备用程序中研究了[] [1,3]恶唑衍生物的结核病。表型筛选针对动素体疾病的代表性实例出乎意料地导致了DNDI-VL-2098的鉴定为潜在的内脏利什曼病（VL）的同类药物候选者。然后进行了其他工作来描述其基本结构特征，目的是在不损害针对VL的活性的情况下提高其溶解度和安全性。尽管4-硝基咪唑部分是特别需要的，但对芳氧基侧链的一些修饰是很好的耐受性，例如，将连接的氧交换成氮（或哌嗪），联芳基延伸以及用吡啶取代苯环。几种较不亲脂的类似物显示出改善的水溶性，尽管对肝微粒体的稳定性变化很大，但特别是在低pH下。在评估小鼠急性模型后利什曼原虫多诺万尼感染中，一种苯基吡啶衍生物（37）脱颖而出，其功效超过了临床前的先导药物。
• [EN] METHOD OF PRODUCING AMINOPHENOL COMPOUNDS<br/>[FR] PROCEDE DE FABRICATION DE COMPOSES AMINOPHENOLS
  申请人：OTSUKA PHARMA CO LTD

  公开号：WO2005092832A1

  公开（公告）日：2005-10-06

  The present invention provides an industrially advantageous method of producing aminophenol compounds represented by the formula (1) by a simple and easy procedure at a high yield and a high purity. The present invention provides a method of producing an aminophenol compound represented by the formula (1): (wherein each of R1 and R2, which may be the same or different, is a hydrogen atom, a substituted or unsubstituted lower alkyl group or the like; R1 and R2, taken together with the adjacent nitrogen atom, may form a 5- or 6-membered heterocycle with or without other intervening heteroatoms; the heterocycle may be substituted by 1 to 3 substituents selected from the group consisting of a hydroxyl group, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aryloxy group and the like; and the hydroxyl group in the formula (1) is substituted on the 2- or 4-position to the amino group on the phenyl ring), which comprises allowing a cyclohexanedione compound represented by the formula (2) to react with an amine compound represented by the formula (3) (wherein R1 and R2 are as defined above), under a neutral or basic condition.

  本发明提供一种在高产率和高纯度下通过简单易行的程序生产由式（1）表示的氨基酚化合物的工业上有利的方法。本发明提供了一种生产由式（1）表示的氨基酚化合物的方法：（其中R1和R2中的每一个，可能相同也可能不同，是氢原子，取代或未取代的较低烷基基团或类似物；R1和R2与相邻氮原子一起可以形成5或6成员的杂环，有或无其他插入的杂原子；该杂环可以被1至3个取代基取代，所述取代基选自羟基团、取代或未取代的较低烷基基团、取代或未取代的芳基基团、取代或未取代的芳氧基团等；并且在式（1）中的羟基团被取代在苯环上的氨基团的2-或4-位置），其包括使由式（2）表示的环己二酮化合物与由式（3）表示的胺化合物（其中R1和R2如上定义）在中性或碱性条件下反应。
• [EN] NITROIMIDAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE NITROIMIDAZOLE
  申请人：GE HEALTHCARE LTD

  公开号：WO2011151320A1

  公开（公告）日：2011-12-08

  The present invention provides novel compounds useful in the treatment and diagnosis of mycobacterial infections. Compounds of the present invention have enhanced biological properties as compared to the related known compounds. The present invention also provides a precursor compound useful in the synthesis of certain compounds of the invention, and a method to obtain these compounds using said precursor compound. Methods of treatment and diagnosis in which the compounds of the invention find use are also provided.

  本发明提供了在治疗和诊断分枝杆菌感染中有用的新化合物。与相关已知化合物相比，本发明的化合物具有增强的生物特性。本发明还提供了一种在合成本发明某些化合物时有用的前体化合物，以及使用该前体化合物获得这些化合物的方法。本发明还提供了利用本发明化合物的治疗和诊断方法。
• [EN] 6-NITRO-2,3-DIHYDROIMIDAZO[2,1-b]OXAZOLES AND A PROCESS FOR THE PREPARATION THEREOF<br/>[FR] 6-NITRO-2,3-DIHYDROIMIDAZO[2,1-B]OXAZOLES ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2015049693A1

  公开（公告）日：2015-04-09

  The present invention relates to newer generation of triazoles, tetrazoles, isoxazoles, urea and sulphonamide functionalities containing 6-nitro-2, 3-dihydronitroimidazooxazoles agents of formula 1, their method of preparation, and their use as drugs for treating Mycobacterium tuberculosis,MDR-TB and XDR-TB either alone or in combination with other anti-tubercular agents. In the present invention, new generation 6-nitro-2, 3-dihydronitroimidazooxazoles agents also show acceptable pharmacokinetic properties and synergistic or additive effects with known anti-tubercular drugs.

  本发明涉及新一代三唑类、四唑类、异噁唑类、尿素和磺胺类功能团的含有6-硝基-2,3-二氢硝基咪唑噁唑类化合物的制备方法，以及它们作为治疗结核分枝杆菌、耐药结核分枝杆菌和极耐药结核分枝杆菌的药物的用途，可以单独使用，也可以与其他抗结核药物联合使用。在本发明中，新一代6-硝基-2,3-二氢硝基咪唑噁唑类化合物还表现出可接受的药代动力学性质，并与已知的抗结核药物呈现协同或加成效应。
• 用于分枝杆菌感染治疗的杂环化合物及其应 用
  申请人：盟科医药技术（上海）有限公司

  公开号：CN106317072B

  公开（公告）日：2020-03-17

  本发明涉及一种用于分枝杆菌感染治疗的杂环化合物及其应用。所述杂环化合物具有如下式I的结构，本发明的杂环化合物具有抗病原性分枝杆菌的活性，有望用于制备哺乳动物感染的治疗药物。