(6R,7S)-2-(2,2-dimethyl-propionyl)-4-(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-[1,2,4]triazin-3-ylsulfanyl)-7-methoxy-3-methyl-5,5-dioxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one | 136933-42-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (6R,7S)-2-(2,2-dimethyl-propionyl)-4-(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-[1,2,4]triazin-3-ylsulfanyl)-7-methoxy-3-methyl-5,5-dioxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one
• 英文别名: (6R,7S)-2-(2,2-Dimethyl-propionyl)-4-(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-[1,2,4]triazin-3-ylsulfanyl)-7-methoxy-3-methyl-5,5-dioxo-5lambda*6*-thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one；3-[[(6R,7S)-2-(2,2-dimethylpropanoyl)-7-methoxy-3-methyl-5,5,8-trioxo-5λ6-thia-1-azabicyclo[4.2.0]oct-2-en-4-yl]sulfanyl]-2-methyl-1H-1,2,4-triazine-5,6-dione
• CAS: 136933-42-1
• 化学式: C₁₇H₂₂N₄O₇S₂
• 分子量: 458.516
• InChiKey: UQXPPXLTKHZSQJ-KHVYEAMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  176
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (6R,7S)-2-(2,2-Dimethyl-propionyl)-7-methoxy-3-methyl-5,5-dioxo-5λ⁶-thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one 在 偶氮二异丁腈 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 三氟乙酸 作用下， 以 四氯化碳 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.17h， 生成 (6R,7S)-2-(2,2-dimethyl-propionyl)-4-(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-[1,2,4]triazin-3-ylsulfanyl)-7-methoxy-3-methyl-5,5-dioxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one
  参考文献：
  名称：

  Synthesis of novel cephem-4-ketones. A new series of human leukocyte elastase inhibitors

  摘要：

  Alkylation of cephem-4-carbonyl chlorides at the sulphide or sulphone oxidation level with Grignard reagents, stannanes and cuprates is described. Radical or ionic bromination of the 3-methylcephem-4-ketone 8, followed by displacement with heterocyclic thiols, provides an entry to 3'-and 2-thiosubstituted derivatives, which are new potent inhibitors of HLE.

  DOI：

  10.1016/0040-4039(91)80790-d

文献信息

• 2,2-Disubstituted cephem sulphones
  申请人：PHARMACIA S.p.A.

  公开号：EP0564835A2

  公开（公告）日：1993-10-13

  The present invention provides cephalosporin sulphones or formula (I), and pharmaceutically or veterinarily acceptable salts thereof; wherein n is zero, one or two;    R₁ is hydrogen, halogen or an optionally substituted C₁-C₄ alkyl, C₂-C₄ alkenyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio or C₁-C₄ carboxamido group;    R₂ is hydrogen or an optionally substituted C₁-C₈ alkyl, C₆-C₁₀ aryl, C₂-C₅ alkenyl or C₃-C₆ cycloalkyl group;    R₃ is hydrogen or acetoxymethyl, methoxymethyl, methyl or an optionally substituted heterocyclylthiomethyl group;    R₄ is an optionally substituted C₁-C₈ alkyl, C₂-C₆ alkenyl, aryl(C₁-C₈)alkyl or heterocyclyl(C₁-C₈)alkyl group; and    R₅ is an optionally substituted C₆-C₁₀ aryl or a heterocyclyl group. The compounds of formula I and the pharmaceutically and veterinarily acceptable salts thereof are elastase inhibitors.

  本发明提供头孢菌素砜或式 (I) 及其药用盐或兽用盐； 其中 n 为 0、1 或 2； R₁ 是氢、卤素或任选取代的 C₁-C₄ 烷基、C₂-C₄ 烯基、C₁-C₄ 烷氧基、C₁-C₄ 烷硫基或 C₁-C₄ 羧氨基； R₂ 是氢或任选取代的 C₁-C₈ 烷基、C₆-C₁₀ 芳基、C₂-C₅ 烯基或 C₃-C₆ 环烷基； R₃ 是氢或乙酰氧甲基、甲氧甲基、甲基或任选取代的杂环硫甲基； R₄ 是任选取代的 C₁-C₈ 烷基、C₂-C₆ 烯基、芳基（C₁-C₈）烷基或杂环烷基（C₁-C₈）烷基；和 R₅ 是任选取代的 C₆-C₁₀ 芳基或杂环基。 式 I 的化合物及其药学上和兽医学上可接受的盐类是弹性蛋白酶抑制剂。
• USE OF CEPHEM DERIVATIVES AS ANTI-METASTATIC AGENTS
  申请人：PHARMACIA & UPJOHN S.p.A.

  公开号：EP0708779B1

  公开（公告）日：1999-01-27
• US5348952A
  申请人：——

  公开号：US5348952A

  公开（公告）日：1994-09-20
• US5580865A
  申请人：——

  公开号：US5580865A

  公开（公告）日：1996-12-03
• Synthesis of novel cephem-4-ketones. A new series of human leukocyte elastase inhibitors
  作者：Marco Alpegiani、Pierluigi Bissolino、Ettore Perrone、Giuseppe Cassinelli、Giovanni Franceschi

  DOI：10.1016/0040-4039(91)80790-d

  日期：1991.10

  Alkylation of cephem-4-carbonyl chlorides at the sulphide or sulphone oxidation level with Grignard reagents, stannanes and cuprates is described. Radical or ionic bromination of the 3-methylcephem-4-ketone 8, followed by displacement with heterocyclic thiols, provides an entry to 3'-and 2-thiosubstituted derivatives, which are new potent inhibitors of HLE.