methyl 4-((trifluoromethylsulfonyloxy)methyl)bicyclo[2.2.2]octane-1-carboxylate | 1350821-97-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: methyl 4-((trifluoromethylsulfonyloxy)methyl)bicyclo[2.2.2]octane-1-carboxylate
• 英文别名: 4-(methoxycarbonyl)bicyclo[2.2.2]octan-1-ylmethyl trifluoromethanesulfonate；Methyl 4-(trifluoromethylsulfonyloxymethyl)bicyclo[2.2.2]octane-1-carboxylate；methyl 4-(trifluoromethylsulfonyloxymethyl)bicyclo[2.2.2]octane-1-carboxylate
• CAS: 1350821-97-4
• 化学式: C₁₂H₁₇F₃O₅S
• 分子量: 330.325
• InChiKey: RSFCKDAJRZBLOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 4-((trifluoromethylsulfonyloxy)methyl)bicyclo[2.2.2]octane-1-carboxylate 在 四丁基氟化铵 、 potassium hydroxide 、 叔丁醇 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 1.5h， 生成 4-(fluoromethyl)bicyclo[2.2.2]octane-1-carboxylic acid
  参考文献：
  名称：

  Design, synthesis and in vitro evaluation of bridgehead fluoromethyl analogs of N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635) for the 5-HT1A receptor

  摘要：

  Fluorinated analogs that are related to the 5-hydroxytryptamine (5-HT1A) antagonist, N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635), have been synthesized and their binding affinity for the 5-HT1A receptor and other neurotransmitter receptors (adrenoceptors, sigma receptors, and dopamine receptors), and serotonin transporters was examined in vitro. These ligands were designed to provide a possible potential positron emission tomography (PET) ligand with high metabolic stability. To this end, the cyclohexyl moiety in WAY-100635 and in O-desmethyl WAY-100635 was replaced by a bridge-fused ring (BFR) such as adamantyl, cubyl, bicyclo[2.2.2] octyl and bicyclo[2.2.1]heptyl to reduce the metabolic rate of the amide bond hydrolysis, while a fluoromethyl group was introduced on the other bridgehead of the BFR to prevent defluorination by HE elimination. All synthesized analogs displayed high affinity in the (sub)nanomolar range for the 5-HT1A receptor, comparable to WAY-100635. In addition, 6b, 6c and 6d were reasonably selective to the 5-HT1A receptor over the above mentioned receptors. In human hepatocytes, 6b showed a suitable metabolic stability.In conclusion, the obtained data provides a promising starting point for the synthesis of the corresponding F-18-labeled PET analogs. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.023
• 作为产物：
  描述：

  4-(羟基甲基)双环[2.2.2]辛烷-1-羧酸甲酯 在 2,6-二甲基吡啶 、 三氟甲磺酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以4.38 g的产率得到methyl 4-((trifluoromethylsulfonyloxy)methyl)bicyclo[2.2.2]octane-1-carboxylate
  参考文献：
  名称：

  [EN] BRIDGED BICYCLIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
  [FR] COMPOSÉS BICYCLIQUES PONTÉS POUR LE TRAITEMENT DES INFECTIONS BACTÉRIENNES

  摘要：

  本文披露了新型桥环双环化合物，以及它们的药用盐、水合物和前药。还披露了包含这些化合物的组合物，制备这些化合物的方法以及将这些化合物用作抗菌剂的方法。所披露的化合物、其药用盐、水合物和前药，以及包含这些化合物、盐、水合物和前药的组合物，可用于治疗细菌感染及相关疾病和症状。

  公开号：

  WO2013003383A1

文献信息

• BRIDGED BICYCLIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
  申请人：Fukuda Yasumichi

  公开号：US20140243302A1

  公开（公告）日：2014-08-28

  Novel bridged bicyclic compounds are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antibacterial agents. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating bacterial infections and associated diseases and conditions.

  本文披露了新型桥环双环化合物及其药学上可接受的盐、水合物和前药。还披露了包含这些化合物的组合物、制备这些化合物的方法以及将这些化合物用作抗菌剂的方法。披露的化合物、它们的药学上可接受的盐、水合物和前药，以及包含这些化合物、盐、水合物和前药的组合物，可用于治疗细菌感染及相关疾病和病情。
• [EN] BRIDGED BICYCLIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS BICYCLIQUES PONTÉS POUR LE TRAITEMENT DES INFECTIONS BACTÉRIENNES
  申请人：KYORIN SEIYAKU KK

  公开号：WO2013003383A1

  公开（公告）日：2013-01-03

  Novel bridged bicyclic compounds are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antibacterial agents. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating bacterial infections and associated diseases and conditions.

  本文披露了新型桥环双环化合物，以及它们的药用盐、水合物和前药。还披露了包含这些化合物的组合物，制备这些化合物的方法以及将这些化合物用作抗菌剂的方法。所披露的化合物、其药用盐、水合物和前药，以及包含这些化合物、盐、水合物和前药的组合物，可用于治疗细菌感染及相关疾病和症状。
• Design, synthesis and in vitro evaluation of bridgehead fluoromethyl analogs of N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635) for the 5-HT1A receptor
  作者：Rana Al Hussainy、Joost Verbeek、Dion van der Born、Jan Booij、J(Koos) D.M. Herscheid

  DOI：10.1016/j.ejmech.2011.06.023

  日期：2011.12

  Fluorinated analogs that are related to the 5-hydroxytryptamine (5-HT1A) antagonist, N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635), have been synthesized and their binding affinity for the 5-HT1A receptor and other neurotransmitter receptors (adrenoceptors, sigma receptors, and dopamine receptors), and serotonin transporters was examined in vitro. These ligands were designed to provide a possible potential positron emission tomography (PET) ligand with high metabolic stability. To this end, the cyclohexyl moiety in WAY-100635 and in O-desmethyl WAY-100635 was replaced by a bridge-fused ring (BFR) such as adamantyl, cubyl, bicyclo[2.2.2] octyl and bicyclo[2.2.1]heptyl to reduce the metabolic rate of the amide bond hydrolysis, while a fluoromethyl group was introduced on the other bridgehead of the BFR to prevent defluorination by HE elimination. All synthesized analogs displayed high affinity in the (sub)nanomolar range for the 5-HT1A receptor, comparable to WAY-100635. In addition, 6b, 6c and 6d were reasonably selective to the 5-HT1A receptor over the above mentioned receptors. In human hepatocytes, 6b showed a suitable metabolic stability.In conclusion, the obtained data provides a promising starting point for the synthesis of the corresponding F-18-labeled PET analogs. (C) 2011 Elsevier Masson SAS. All rights reserved.