2-chloro-1-{[(2S)-2-methyloxiran-2-yl]methyl}-4-nitro-1H-imidazole | 681490-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloro-1-{[(2S)-2-methyloxiran-2-yl]methyl}-4-nitro-1H-imidazole
• 英文别名: (S)-2-chloro-1-(2-methyl-2,3-epoxypropyl)-4-nitroimidazole；(S)-2-chloro-1-(2-methyl-2-oxiranylmethyl)-4-nitroimidazole；(S)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole；2-chloro-1-[[(2S)-2-methyloxiran-2-yl]methyl]-4-nitroimidazole
• CAS: 681490-98-2
• 化学式: C₇H₈ClN₃O₃
• 分子量: 217.612
• InChiKey: SZMDGYNOADBVSR-ZETCQYMHSA-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)

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

反应信息

• 作为反应物：
  描述：

  2-chloro-1-{[(2S)-2-methyloxiran-2-yl]methyl}-4-nitro-1H-imidazole 、 4-氟-4'-羟基联苯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以44%的产率得到(2S)-2-{[(4'-fluoro[1,1'-biphenyl]-4-yl)oxy]methyl}-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole
  参考文献：
  名称：

  重新定位抗结核的6-硝基-2,3-二氢咪唑并[2,1- b ] [1,3]恶唑类药物用于被忽视的热带病：内脏利什曼病的临床前候选者的结构-活性研究

  摘要：

  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。

  DOI：

  10.1021/acs.jmedchem.5b01699
• 作为产物：
  描述：

  (S)-2-chloro-1-(2,3-dihydroxy-2-methyl)-propyl-4-nitroimidazole 在 吡啶 、 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 4.5h， 生成 2-chloro-1-{[(2S)-2-methyloxiran-2-yl]methyl}-4-nitro-1H-imidazole
  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

• 2,3-Dihydro-6-nitroimidazo[2,1-b]oxazoles
  申请人：Tsubouchi Hidetsugu

  公开号：US20060094767A1

  公开（公告）日：2006-05-04

  The present invention provides a 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the following general formula: wherein R 1 represents a hydrogen atom or C1-C6 alkyl group, n represents an integer of 0 to 6, R 2 represents a group —OR 3 or the like, and R 3 represents a hydrogen atom, C1-C6 alkyl group or the like, or R 1 and —(CH 2 ) n R 2 may bind to each other together with carbon atoms adjacent thereto through nitrogen atoms so as to form a spiro ring represented by the general formula (H): wherein R 41 is hydrogen, C1-C6 alkyl group or the like. The present compound has an excellent bactericidal action against Mycobacterium tuberculosis , multi-drug-resistant Mycobacterium tuberculosis , and atypical acid-fast bacteria.

  本发明提供了一种2,3-二氢-6-硝基咪唑并[2,1-b]噁唑化合物，其通式如下：其中，R1代表氢原子或C1-C6烷基，n代表0到6的整数，R2代表—OR3或类似的基团，R3代表氢原子、C1-C6烷基或类似的基团，或者R1和—(CH2)nR2可以通过相邻的碳原子通过氮原子结合在一起形成一个螺环，其通式为（H）：其中，R41为氢、C1-C6烷基或类似的基团。该化合物对结核分枝杆菌、多药耐药结核分枝杆菌和非典型酸性快速细菌具有优异的杀菌作用。
• 1-substituted-4-nitroimidazole compound and process for producing the same
  申请人：Goto Fumitake

  公开号：US20060079697A1

  公开（公告）日：2006-04-13

  The present invention relates to a 1-substituted-4-nitroimidazole compound represented by the general formula (1) or a salt thereof, (wherein R is a hydrogen atom, a lower alkoxy group-substituted lower alkyl group, a phenyl-lower alkoxy group-substituted lower alkyl group, a cyano-substituted lower alkyl group, a phenyl-lower alkyl group which may have lower alkoxy groups as the substituents in the phenyl ring or a group of the formula —CH 2 R A ; X is a halogen atom or a group of the formula —S(O)n—R 1 ) and method for preparing the same. The compound of the formula (1) is a useful compound as an intermediate for synthesis of various pharmaceutical and agricultural chemicals, particularly, as intermediates for antitubercular agents.

  本发明涉及一种1-取代-4-硝基咪唑化合物，其通式为（1），或其盐，其中R是氢原子，低烷氧基取代的低烷基，苯基-低烷氧基取代的低烷基，氰基取代的低烷基，苯基-低烷基（苯环上可能有低烷氧基取代物）或式子-CH2RA的基团；X是卤素原子或式子-S(O)n-R1的基团。本发明还涉及其制备方法。式（1）的化合物是一种有用的化合物，可用作合成各种药物和农药化学品的中间体，特别是抗结核药物的中间体。
• 1-Substituted-4-nitroimidazole compound and method for preparing the same
  申请人：Goto Fumitaka

  公开号：US20080200689A1

  公开（公告）日：2008-08-21

  The present invention relates to a 1-substituted-4-nitroimidazole compound represented by the general formula (1) or a salt thereof, (wherein R is a hydrogen atom, a lower alkoxy group-substituted lower alkyl group, a phenyl-lower alkoxy group-substituted lower alkyl group, a cyano-substituted lower alkyl group, a phenyl-lower alkyl group which may have lower alkoxy groups as the substituents in the phenyl ring or a group of the formula —CH 2 R A ; X is a halogen atom or a group of the formula —S(O)n-R 1 ) and method for preparing the same. The compound of the formula (1) is a useful compound as an intermediate for synthesis of various pharmaceutical and agricultural chemicals, particularly, as intermediates for antitubercular agents.

  本发明涉及一种由通式（1）表示的1-取代-4-硝基咪唑化合物或其盐（其中R是氢原子、较低烷氧基取代的较低烷基、苯基-较低烷氧基取代的较低烷基、氰基取代的较低烷基、苯基-较低烷基（苯环上可能存在较低烷氧基作为取代基）或式子—CH2RA的基团；X是卤素原子或式子—S（O）n-R1的基团），以及其制备方法。通式（1）的化合物是一种有用的化合物，可用作合成各种药物和农药化学品的中间体，特别是用作抗结核药物的中间体。
• 2,3-dihydro-6-nitroimidazo[2,1-b]oxazoles
  申请人：Otsuka Pharmaceutical Co., Ltd.

  公开号：US07262212B2

  公开（公告）日：2007-08-28

  The present invention provides a 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the following general formula: wherein R1 represents a hydrogen atom or C1-C6 alkyl group, n represents an integer of 0 to 6, R2 represents a group —OR3 or the like, and R3 represents a hydrogen atom, C1-C6 alkyl group or the like, or R1 and —(CH2)nR2 may bind to each other together with carbon atoms adjacent thereto through nitrogen atoms so as to form a spiro ring represented by the general formula (H): wherein R41 is hydrogen, C1-C6 alkyl group or the like. The present compound has an excellent bactericidal action against Mycobacterium tuberculosis, multi-drug-resistant Mycobacterium tuberculosis, and atypical acid-fast bacteria.

  本发明提供一种由以下通式表示的2,3-二氢-6-硝基咪唑并[2,1-b]噁唑化合物：其中R1代表氢原子或C1-C6烷基，n代表0到6的整数，R2代表-OR3基团或类似基团，R3代表氢原子、C1-C6烷基或类似基团，或R1和-(CH2)nR2可以与相邻的碳原子通过氮原子结合在一起，形成由通式（H）表示的螺环：其中R41是氢、C1-C6烷基或类似基团。该化合物对结核分枝杆菌、多药耐药结核分枝杆菌和非典型酸性快速菌具有优异的杀菌作用。
• 1-substituted-4-nitroimidazole compound and method for preparing the same
  申请人：Goto Fumitaka

  公开号：US20080097107A1

  公开（公告）日：2008-04-24

  The present invention relates to a 1-substituted-4-nitroimidazole compound represented by the general formula (1) or a salt thereof, (wherein R is a hydrogen atom, a lower alkoxy group-substituted lower alkyl group, a phenyl-lower alkoxy group-substituted lower alkyl group, a cyano-substituted lower alkyl group, a phenyl-lower alkyl group which may have lower alkoxy groups as the substituents in the phenyl ring or a group of the formula —CH 2 R A ; X is a halogen atom or a group of the formula —S(O)n-R 1 ) and method for preparing the same. The compound of the formula (1) is a useful compound as an intermediate for synthesis of various pharmaceutical and agricultural chemicals, particularly, as intermediates for antitubercular agents.

  本发明涉及一种由通式（1）表示的1-取代-4-硝基咪唑化合物或其盐，其中R是氢原子、低位烷氧基取代的低碳基、苯基-低位烷氧基取代的低碳基、氰基取代的低碳基、苯基-低碳基（苯环上可能有低位烷氧基取代物）或公式-CH2RA的基团；X是卤素原子或公式-S（O）n-R1的基团。本发明还涉及制备该化合物的方法。式（1）的化合物是一种有用的化合物，可用作合成各种制药和农业化学品的中间体，特别是抗结核药物的中间体。