(6S)-6-{[3-(4-bromophenyl)-2-propynyl]oxy}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine | 1263417-39-5

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (6S)-6-{[3-(4-bromophenyl)-2-propynyl]oxy}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
• 英文别名: (6S)-6-[3-(4-bromophenyl)prop-2-ynoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
• CAS: 1263417-39-5
• 化学式: C₁₅H₁₂BrN₃O₄
• 分子量: 378.182
• InChiKey: QJROUIBSMZFEJP-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6S)-6-{[3-(4-bromophenyl)-2-propynyl]oxy}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine 、 4-三氟甲氧基苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 0.5h， 以72%的产率得到(6S)-2-nitro-6-({3-[4'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl]-2-propynyl}oxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Varied Ether Linker Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)

  摘要：

  New analogues of antitubercular drug PA-824 were synthesized, featuring alternative side chain ether linkers of varying size and flexibility, seeking drug candidates with enhanced metabolic stability and high efficacy. Both alpha-methyl substitution and removal of the benzylic methylene were broadly tolerated in vitro, with a biaryl example of the latter class exhibiting an 8-fold better efficacy than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection and negligible fragmentation to an alcohol metabolite in liver microsomes. Extended linkers (notably propenyloxy, propynyloxy, and pentynyloxy) provided greater potencies against replicating M. tb (monoaryl analogues), with propynyl ethers being most effective under anaerobic (nonreplicating) conditions (mono/biaryl analogues). For benzyloxybenzyl and biaryl derivatives, aerobic activity was maximal with the original (OCH2) linker. One propynyloxy-linked compound displayed an 89-fold higher efficacy than the parent drug in the acute model, and it was slightly superior to antitubercular drug OPC-67683 in a chronic infection model.

  DOI：

  10.1021/jm200377r
• 作为产物：
  描述：

  3-(4-溴苯基)-2-丙炔-1-醇 在 吡啶 、 三溴化磷 、 sodium hydride 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.5h， 生成 (6S)-6-{[3-(4-bromophenyl)-2-propynyl]oxy}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Varied Ether Linker Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)

  摘要：

  New analogues of antitubercular drug PA-824 were synthesized, featuring alternative side chain ether linkers of varying size and flexibility, seeking drug candidates with enhanced metabolic stability and high efficacy. Both alpha-methyl substitution and removal of the benzylic methylene were broadly tolerated in vitro, with a biaryl example of the latter class exhibiting an 8-fold better efficacy than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection and negligible fragmentation to an alcohol metabolite in liver microsomes. Extended linkers (notably propenyloxy, propynyloxy, and pentynyloxy) provided greater potencies against replicating M. tb (monoaryl analogues), with propynyl ethers being most effective under anaerobic (nonreplicating) conditions (mono/biaryl analogues). For benzyloxybenzyl and biaryl derivatives, aerobic activity was maximal with the original (OCH2) linker. One propynyloxy-linked compound displayed an 89-fold higher efficacy than the parent drug in the acute model, and it was slightly superior to antitubercular drug OPC-67683 in a chronic infection model.

  DOI：

  10.1021/jm200377r

文献信息

• [EN] NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY<br/>[FR] NITROIMIDAZOOXAZINES ET LEURS UTILISATIONS EN THÉRAPIE ANTITUBERCULEUSE
  申请人：GLOBAL ALLIANCE FOR TB DRUG DEV

  公开号：WO2011014774A1

  公开（公告）日：2011-02-03

  The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗方法结合使用。
• NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY
  申请人：Denny William Alexander

  公开号：US20120028973A1

  公开（公告）日：2012-02-02

  The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗联合使用。
• US9198913B2
  申请人：——

  公开号：US9198913B2

  公开（公告）日：2015-12-01