4-(fluoromethyl)bicyclo[2.2.1]heptane-1-carboxylic acid | 1350821-85-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 4-(fluoromethyl)bicyclo[2.2.1]heptane-1-carboxylic acid
• 英文别名: 4-(Fluoromethyl)bicyclo[2.2.1]heptane-1-carboxylic acid
• CAS: 1350821-85-0
• 化学式: C₉H₁₃FO₂
• 分子量: 172.199
• InChiKey: ZLWBFLQHSMDVBF-UHFFFAOYSA-N

物化性质

• 沸点：
  271.7±5.0 °C(Predicted)
• 密度：
  1.289±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(fluoromethyl)bicyclo[2.2.1]heptane-1-carboxylic acid 在 氯化亚砜 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成
  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-(甲氧基羰基)双环[2.2.1]庚烷-1-甲酸 在 吡啶 、 dimethyl sulfide borane 、 四丁基氟化铵 、 potassium hydroxide 、 叔丁醇 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 3.5h， 生成 4-(fluoromethyl)bicyclo[2.2.1]heptane-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

文献信息

• NOVEL SUBSTITUTED PYRAZOLO-PIPERAZINES AS CASEIN KINASE 1 D/E INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150133428A1

  公开（公告）日：2015-05-14

  The invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof. The compounds of Formula (I) inhibit protein kinase activity thereby making them useful as anticancer agents.

  本发明提供式(I)的化合物及其药学上可接受的盐。式(I)的化合物抑制蛋白激酶活性，因此具有作为抗癌剂的用途。
• SUBSTITUTED 4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRAZINE DERIVATIVES AS CASEIN KINASE 1 D/E INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP3068785A1

  公开（公告）日：2016-09-21
• US9273058B2
  申请人：——

  公开号：US9273058B2

  公开（公告）日：2016-03-01
• [EN] SUBSTITUTED 4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRAZINE DERIVATIVES AS CASEIN KINASE 1 D/E INHIBITORS<br/>[FR] DÉRIVÉS DE 4,5,6,7-TÉTRAHYDROPYRAZOLO[1,5-A]PYRAZINE SUBSTITUÉS EN TANT QU'INHIBITEURS DE CASÉINE KINASE 1 D/E
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015073763A1

  公开（公告）日：2015-05-21

  The invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof. The compounds of Formula (I) inhibit protein kinase activity thereby making them useful as anticancer agents.
• 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.