美他唑嗪 | 95549-92-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 美他唑嗪
• 英文名称: 1-(4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl)-2-methoxypropan-1-one
• 英文别名: 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-methoxypropionyl)-piperazine；1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-methoxyproprionyl)piperazine；metazosin；1-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-2-methoxypropan-1-one
• CAS: 95549-92-1
• 化学式: C₁₈H₂₅N₅O₄
• 分子量: 375.428
• InChiKey: YEOTYALSMRNXLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

制备方法与用途

美他唑嗪（Kenosin）是一种有效的α1肾上腺素受体阻滞剂，也是一种常用的降压药。

反应信息

• 作为反应物：
  描述：

  美他唑嗪 生成 1-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-2-methoxypropan-1-one;hydrate;hydrochloride
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  2-甲氧基丙酸 、 2-哌嗪基-4-氨基-6,7-二甲氧基喹唑啉 在 N,N-二异丙基乙胺 、 2-肟氰乙酸乙酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以52%的产率得到美他唑嗪
  参考文献：
  名称：

  Targeting Influenza A Virus RNA Promoter

  摘要：

  The emergence of drug‐resistant strains of influenza virus makes exploring new classes of inhibitors that target universally conserved viral targets a highly important goal. The influenza A viral genome is made up of eight single‐stranded RNA‐negative segments. The RNA promoter, consisting of the conserved sequences at the 3′ and 5′ end of each RNA genomic segment, is universally conserved among influenza A virus strains and in all segments. Previously, we reported on the identification and NMR structure of DPQ (6,7‐dimethoxy‐2‐(1‐piperazinyl)‐4‐quinazolinamine) (compound 1) in complex with the RNA promoter. Here, we report on additional screening and SAR studies with compound 1, including ex vivo anti‐influenza activity assays, resulted in improved cellular activity against influenza A virus in the micromolar range.

  DOI：

  10.1111/cbdd.12534

文献信息

• Substituted acylpiperazinoquinazolines and pharmaceutical compositions
  申请人：SPOFA, spojene podniky pro zdravotnickou vyrobu

  公开号：US04775673A1

  公开（公告）日：1988-10-04

  Substituted acylpiperazinoquinazolines of formula I ##STR1## wherein n is 0 or 1, R represents an alkyl group with 1 to 4 carbon atoms or a benzyl group, and R.sub.1 is a hydrogen atom, a methyl group or a phenyl group. Addition salts of these compounds with inorganic and organic acids are also disclosed. The compounds possess a significant antihypertensive activity. They can be prepared by the reaction of 2-halogeno quinazoline derivatives with the corresponding acylpiperazines, followed (if required) by neutralization of the respective base with a suitable acid to form its pharmaceutically convenient addition salt. The acid addition salts, especially hydrochlorides, are readily soluble in water and give stable, almost neutral aqueous solutions which can be used in parenteral (injectable) and peroral medicinal dosage forms.

  式I的取代酰基哌嗪喹唑啉化合物##STR1##其中n为0或1，R代表具有1至4个碳原子的烷基或苄基，R.sub.1为氢原子、甲基或苯基。还披露了这些化合物与无机和有机酸的加成盐。这些化合物具有显著的降压活性。它们可以通过2-卤代喹唑啉衍生物与相应的酰基哌嗪反应制备，随后（如有必要）通过用适当酸中和相应碱来形成其药学上方便的加成盐。酸加成盐，特别是盐酸盐，在水中易溶且形成稳定、几乎中性的水溶液，可用于肌注和口服药物剂型。
• ——
  作者：KONIG J.、 RAJSNER M.、 TRCKA V.、 MACOVA S.

  DOI：——

  日期：——
• US4775673A
  申请人：——

  公开号：US4775673A

  公开（公告）日：1988-10-04
• Targeting Influenza A Virus RNA Promoter
  作者：Angel Bottini、Surya K. De、Bainan Wu、Changyan Tang、Gabriele Varani、Maurizio Pellecchia

  DOI：10.1111/cbdd.12534

  日期：2015.10

  The emergence of drug‐resistant strains of influenza virus makes exploring new classes of inhibitors that target universally conserved viral targets a highly important goal. The influenza A viral genome is made up of eight single‐stranded RNA‐negative segments. The RNA promoter, consisting of the conserved sequences at the 3′ and 5′ end of each RNA genomic segment, is universally conserved among influenza A virus strains and in all segments. Previously, we reported on the identification and NMR structure of DPQ (6,7‐dimethoxy‐2‐(1‐piperazinyl)‐4‐quinazolinamine) (compound 1) in complex with the RNA promoter. Here, we report on additional screening and SAR studies with compound 1, including ex vivo anti‐influenza activity assays, resulted in improved cellular activity against influenza A virus in the micromolar range.