(E/Z)-6,6-dimethylhept-2-ene-4-ynal | 114311-71-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (E/Z)-6,6-dimethylhept-2-ene-4-ynal
• 英文别名: 6,6-Dimethyl-2-hepten-4-ynal；6,6-dimethylhept-2-en-4-ynal
• CAS: 114311-71-6
• 化学式: C₉H₁₂O
• 分子量: 136.194
• InChiKey: ITSLKJVPPOREBI-UHFFFAOYSA-N

物化性质

• 沸点：
  197.0±23.0 °C(Predicted)
• 密度：
  0.899±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-乙酰-L-半胱氨酸 、 (E/Z)-6,6-dimethylhept-2-ene-4-ynal 以 水 、 乙腈 为溶剂， 反应 3.5h， 生成 、
  参考文献：
  名称：

  Identification of a Reactive Metabolite of Terbinafine:  Insights into Terbinafine-Induced Hepatotoxicity

  摘要：

  Oral terbinafine treatment for superficial fungal infections of toe and fingernails is associated with a low incidence (1:45000) of hepatobiliary dysfunction. Due to the rare and unpredictable nature of this adverse drug reaction, the mechanism of toxicity has been hypothesized to be either an uncommon immunological or metabolically mediated effect. However, there is little evidence to support either mechanism, and toxic metabolites of terbinafine have not been identified. We incubated terbinafine with both rat and human liver microsomal protein in the presence of GSH and were able to trap an allylic aldehyde, 7,7-dimethylhept-2-ene-4-ynal (TBFA), which corresponds to the N-dealkylation product of terbinafine. TBF-A was also prepared synthetically and reacted with excess GSH to yield conjugates with HPLC retention times and mass spectra identical to those generated in the microsomal incubations. The major GSH conjugate, characterized by H-1 NMR, corresponds to addition of GSH in a 1,6-Michael fashion. There remains a second electrophilic site on this metabolite, which can bind either to a second molecule of GSH or to cellular proteins via a 1,4-Michael addition mechanism. Moreover, we demonstrated that the formation of the GSH conjugates was reversible. We speculate that this allylic aldehyde metabolite, formed by liver enzymes and conjugated with GSH, would be transported across the canalicular membrane of hepatocytes and concentrated in the bile. The mono-GSH conjugate, which is still reactive, could bind to hepatobiliary proteins and lead to direct toxicity. Alternatively, it could modify canalicular proteins and lead to an immune-mediated reaction causing cholestatic dysfunction.

  DOI：

  10.1021/tx0002029
• 作为产物：
  描述：

  (E/Z)-6,6-dimethylhept-2-ene-4-ynol 在 manganese dioxide 二氯甲烷 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 以afforded 2.74 g of 6,6-dimethyl-2-hepten-4-ynal的产率得到(E/Z)-6,6-dimethylhept-2-ene-4-ynal
  参考文献：
  名称：

  Antifungal derivatives of

  摘要：

  提供具有一般式为##STR1##的N-(6,6-二甲基-2-庚烯-4-亚乙炔基)-1-萘甲胺衍生物，其中R.sub.1是甲氧基，亚胺甲基或1-亚胺乙基，R.sub.2和R.sub.3均为氢；或R.sub.1为甲基，R.sub.2和R.sub.3中的一个是氢，另一个是卤素。上述化合物及其酸加成盐可用作抗真菌剂。

  公开号：

  US04751245A1

文献信息

• Identification of a Reactive Metabolite of Terbinafine:  Insights into Terbinafine-Induced Hepatotoxicity
  作者：Suzanne L. Iverson、Jack P. Uetrecht

  DOI：10.1021/tx0002029

  日期：2001.2.1

  Oral terbinafine treatment for superficial fungal infections of toe and fingernails is associated with a low incidence (1:45000) of hepatobiliary dysfunction. Due to the rare and unpredictable nature of this adverse drug reaction, the mechanism of toxicity has been hypothesized to be either an uncommon immunological or metabolically mediated effect. However, there is little evidence to support either mechanism, and toxic metabolites of terbinafine have not been identified. We incubated terbinafine with both rat and human liver microsomal protein in the presence of GSH and were able to trap an allylic aldehyde, 7,7-dimethylhept-2-ene-4-ynal (TBFA), which corresponds to the N-dealkylation product of terbinafine. TBF-A was also prepared synthetically and reacted with excess GSH to yield conjugates with HPLC retention times and mass spectra identical to those generated in the microsomal incubations. The major GSH conjugate, characterized by H-1 NMR, corresponds to addition of GSH in a 1,6-Michael fashion. There remains a second electrophilic site on this metabolite, which can bind either to a second molecule of GSH or to cellular proteins via a 1,4-Michael addition mechanism. Moreover, we demonstrated that the formation of the GSH conjugates was reversible. We speculate that this allylic aldehyde metabolite, formed by liver enzymes and conjugated with GSH, would be transported across the canalicular membrane of hepatocytes and concentrated in the bile. The mono-GSH conjugate, which is still reactive, could bind to hepatobiliary proteins and lead to direct toxicity. Alternatively, it could modify canalicular proteins and lead to an immune-mediated reaction causing cholestatic dysfunction.
• Antifungal derivatives of
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04751245A1

  公开（公告）日：1988-06-14

  N-(6,6-dimethyl-2-hepten-4-ynyl)-1-naphthalenemethanamine derivatives are provided having the general formula ##STR1## wherein R.sub.1 is methoxy, iminomethyl or 1-iminoethyl and R.sub.2 and R.sub.3 are each hydrogen; or R.sub.1 is methyl and one of R.sub.2 and R.sub.3 is hydrogen and the other is halogen. The above compounds as well as acid-addition salts thereof are useful as antifungal agents.

  提供具有一般式为##STR1##的N-(6,6-二甲基-2-庚烯-4-亚乙炔基)-1-萘甲胺衍生物，其中R.sub.1是甲氧基，亚胺甲基或1-亚胺乙基，R.sub.2和R.sub.3均为氢；或R.sub.1为甲基，R.sub.2和R.sub.3中的一个是氢，另一个是卤素。上述化合物及其酸加成盐可用作抗真菌剂。