(R)-2-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-yl)ethyl 4'-(trifluoromethoxy) biphenyl-4-ylcarbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-2-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-yl)ethyl 4'-(trifluoromethoxy) biphenyl-4-ylcarbamate
• 英文别名: 2-[(7R)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-yl]ethyl N-[4-[4-(trifluoromethoxy)phenyl]phenyl]carbamate
• 化学式: C₂₂H₁₉F₃N₄O₆
• 分子量: 492.411
• InChiKey: RWIIHKJBEBJNPA-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1,3,5-戊三醇 在 4-二甲氨基吡啶 、 四丁基碘化铵 、 potassium carbonate 、 caesium carbonate 、 对甲苯磺酸 、 copper(l) chloride 、 原甲酸三甲酯 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.5h， 生成 (R)-2-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-yl)ethyl 4'-(trifluoromethoxy) biphenyl-4-ylcarbamate
  参考文献：
  名称：

  Synthesis and anti-tubercular activity of 2-nitroimidazooxazines with modification at the C-7 position as PA-824 analogs

  摘要：

  Tuberculosis (TB) is a major global health problem, and new drug targets and scaffolds need to be identified to combat the emergence of drug resistant TB.The nitroimidazooxazine PA-824 represents a new class of bio-reductive drug to treat TB. In this study we report a 2-nitroimidazooxazine derivative with modification at the C-7 position that exhibited better activity than PA-824 against Mycobacterium tuberculosis (Mtb) H37Rv strain in vitro. From 7a as a key intermediate, we functionalized with benzyl ether (8), phenyl ether (9), benzyl carbonate (10) and benzyl carbamate (11). Among the 23 compounds produced, 8a-R (MIC = 0.078 mu M) with trifluoromethoxy benzyl group was 5-fold more potent than PA-824 (MIC = 0.390 mu M) in the in vitro assays against the wild-type Mtb, and the phenyl ether compound 9g-R (MIC = 0.050 mu M) exhibited the most potent antimycobacterial activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.060

文献信息

• 이미다조 옥사진 유도체, 이의 약학적으로 허용 가능한 염 또는 이의 광학이성질체 및 이를 유효성분으로 함유하는 약제학적 조성물
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY 한국화학연구원(319980077651)

  公开号：KR20160052048A

  公开（公告）日：2016-05-12

  본 발명은 이미다조 옥사진 유도체, 이의 약학적으로 허용 가능한 염 또는 이의 광학이성질체 및 이를 유효성분으로 함유하는 약제학적 조성물에 관한 것으로, 7번 위치가 치환된 2-니트로-6,7-디하이드로이미다졸[2,1-b][1,3]옥사진의 유도체 이의 약학적으로 허용 가능한 염 또는 이의 광학이성질체는 결핵균, 특히 비활동성 결핵균에 대한 억제 효과가 우수하여 이를 유효성분으로 함유하는 결핵질환 치료용 약제학적 조성물로서 유용하게 사용될 수 있다.

  这项发明涉及一种已被置换的2-硝基-6,7-二氢咪唑[2,1-b][1,3]氧杂吲哚的衍生物，其药学上可接受的盐或其光学异构体，以及包含它们作为有效成分的药学组合物，具有对结核菌，特别是对非活动结核菌的抑制作用优越，可用作包含它们作为有效成分的结核病治疗药学组合物，具有很好的应用前景。
• Synthesis and anti-tubercular activity of 2-nitroimidazooxazines with modification at the C-7 position as PA-824 analogs
  作者：Young-Goo Kang、Chan-Yong Park、Hongsuk Shin、Ramandeep Singh、Garima Arora、Chan-mo Yu、Ill Young Lee

  DOI：10.1016/j.bmcl.2015.06.060

  日期：2015.9

  Tuberculosis (TB) is a major global health problem, and new drug targets and scaffolds need to be identified to combat the emergence of drug resistant TB.The nitroimidazooxazine PA-824 represents a new class of bio-reductive drug to treat TB. In this study we report a 2-nitroimidazooxazine derivative with modification at the C-7 position that exhibited better activity than PA-824 against Mycobacterium tuberculosis (Mtb) H37Rv strain in vitro. From 7a as a key intermediate, we functionalized with benzyl ether (8), phenyl ether (9), benzyl carbonate (10) and benzyl carbamate (11). Among the 23 compounds produced, 8a-R (MIC = 0.078 mu M) with trifluoromethoxy benzyl group was 5-fold more potent than PA-824 (MIC = 0.390 mu M) in the in vitro assays against the wild-type Mtb, and the phenyl ether compound 9g-R (MIC = 0.050 mu M) exhibited the most potent antimycobacterial activity. (C) 2015 Elsevier Ltd. All rights reserved.