tert-butyl (RR,SS)-2-cyano-3-(2-methoxyphenyl)-2-methyl-3-(1-naphthyl)propanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl (RR,SS)-2-cyano-3-(2-methoxyphenyl)-2-methyl-3-(1-naphthyl)propanoate
• 英文别名: Tert-butyl 2-cyano-3-(2-methoxyphenyl)-2-methyl-3-naphthalen-1-ylpropanoate
• 化学式: C₂₆H₂₇NO₃
• 分子量: 401.505
• InChiKey: IPZOUOZDIYMKQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (RR,SS)-2-cyano-3-(2-methoxyphenyl)-2-methyl-3-(1-naphthyl)propanoate 生成 tert-butyl (S,S)-2-cyano-3-(2-methoxyphenyl)-2-methyl-3-(1-naphthyl)propanoate 、 tert-butyl (R,R)-2-cyano-3-(2-methoxyphenyl)-2-methyl-3-(1-naphthyl)propanoate
  参考文献：
  名称：

  Estrogen Receptor Dependent Inhibitors of NF-κB Transcriptional Activation-1 Synthesis and Biological Evaluation of Substituted 2-Cyanopropanoic Acid Derivatives:  Pathway Selective Inhibitors of NF-κB, a Potential Treatment for Rheumatoid Arthritis

  摘要：

  Pathway selective ligands of the estrogen receptor inhibit transcriptional activation of proinflammatory genes mediated by NF kappa B. Substituted 2-cyanopropanoic acid derivatives were developed leading to the discovery of WAY-204688, an orally active, pathway selective, estrogen receptor dependent anti-inflammatory agent. This propanamide was shown to be orally active in preclinical models of inflammatory diseases, such as rheumatoid arthritis, without the proliferative effect associated with traditional, estrogens.

  DOI：

  10.1021/jm701013k
• 作为产物：
  描述：

  2-cyano-3-(2-methoxyphenyl)-3-naphthalen-1-yl-propionic acid tert-butyl ester 、 碘甲烷 在 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.0h， 以700 mg的产率得到tert-butyl (RR,SS)-2-cyano-3-(2-methoxyphenyl)-2-methyl-3-(1-naphthyl)propanoate
  参考文献：
  名称：

  Estrogen Receptor Dependent Inhibitors of NF-κB Transcriptional Activation-1 Synthesis and Biological Evaluation of Substituted 2-Cyanopropanoic Acid Derivatives:  Pathway Selective Inhibitors of NF-κB, a Potential Treatment for Rheumatoid Arthritis

  摘要：

  Pathway selective ligands of the estrogen receptor inhibit transcriptional activation of proinflammatory genes mediated by NF kappa B. Substituted 2-cyanopropanoic acid derivatives were developed leading to the discovery of WAY-204688, an orally active, pathway selective, estrogen receptor dependent anti-inflammatory agent. This propanamide was shown to be orally active in preclinical models of inflammatory diseases, such as rheumatoid arthritis, without the proliferative effect associated with traditional, estrogens.

  DOI：

  10.1021/jm701013k

文献信息

• Use of ER selective NF-kB inhibitors for the treatment of sepsis
  申请人：Caggiano J. Thomas

  公开号：US20050256132A1

  公开（公告）日：2005-11-17

  The present invention provides methods for treating sepsis, systemic inflammatory response syndrome, severe sepsis, septic shock, and multiple organ dysfunction syndrome by modulating NF-κB transcription with ligands that interact with the estrogen receptor, preferably in the absence of classic estrogenic activity. Other aspects of the invention relate to methods for treating sepsis, systemic inflammatory response syndrome, severe sepsis, septic shock, and multiple organ dysfunction syndrome that comprise administering to a patient suffering therefrom an effective amount of a compound of Formula I:

  本发明提供了通过调节与雌激素受体相互作用的配体来调节NF-κB转录，从而治疗脓毒症、全身性炎症反应综合征、严重脓毒症、脓毒性休克和多器官功能障碍综合征的方法，优选在无典型雌激素活性的情况下进行。本发明的其他方面涉及治疗脓毒症、全身性炎症反应综合征、严重脓毒症、脓毒性休克和多器官功能障碍综合征的方法，包括向患有此类病症的患者施用有效量的式I化合物：
• Estrogen Receptor Dependent Inhibitors of NF-κB Transcriptional Activation-1 Synthesis and Biological Evaluation of Substituted 2-Cyanopropanoic Acid Derivatives:  Pathway Selective Inhibitors of NF-κB, a Potential Treatment for Rheumatoid Arthritis
  作者：Thomas J. Caggiano、Antony Brazzale、Douglas M. Ho、Christina M. Kraml、Eugene Trybulski、Christopher C. Chadwick、Sue Chippari、Lisa Borges-Marcucci、Amy Eckert、James C. Keith、Thomas Kenney、Douglas C. Harnish

  DOI：10.1021/jm701013k

  日期：2007.11.1

  Pathway selective ligands of the estrogen receptor inhibit transcriptional activation of proinflammatory genes mediated by NF kappa B. Substituted 2-cyanopropanoic acid derivatives were developed leading to the discovery of WAY-204688, an orally active, pathway selective, estrogen receptor dependent anti-inflammatory agent. This propanamide was shown to be orally active in preclinical models of inflammatory diseases, such as rheumatoid arthritis, without the proliferative effect associated with traditional, estrogens.