(R)-3-(4-(6-fluoropyridin-3-yl)-1H-1,2,3-triazol-1-yl) quinuclidine | 1403993-16-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R)-3-(4-(6-fluoropyridin-3-yl)-1H-1,2,3-triazol-1-yl) quinuclidine
• 英文别名: (R)-3-(4-(6-fluoropyridin-3-yl)-1H-1,2,3-triazol-1-yl)quinuclidine；(3R)-3-[4-(6-fluoropyridin-3-yl)triazol-1-yl]-1-azabicyclo[2.2.2]octane
• CAS: 1403993-16-7
• 化学式: C₁₄H₁₆FN₅
• 分子量: 273.313
• InChiKey: BFHAQTHGFRDUIW-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (3R)-1-氮杂双环[2.2.2]辛烷-3-胺盐酸盐(1:1) 在 1H-咪唑-1-磺酰叠氮盐酸盐 、 copper(ll) sulfate pentahydrate 、 potassium carbonate 、 sodium ascorbate 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 (R)-3-(4-(6-fluoropyridin-3-yl)-1H-1,2,3-triazol-1-yl) quinuclidine
  参考文献：
  名称：

  Design of α7 nicotinic acetylcholine receptor ligands using the (het)Aryl-1,2,3-triazole core: Synthesis, in vitro evaluation and SAR studies

  摘要：

  We report here the synthesis of a large library of 1,2,3-triazole derivatives which were in vitro tested as alpha 7 nAchR ligands. The SAR study revealed that several crucial factors are involved in the affinity of these compounds for alpha 7 nAchR such as a (R) quinuclidine configuration and a mono C-3 quinuclidine substitution. The triazole ring was substituted by a phenyl ring bearing small OMe/CH2F groups or fluorine atom and by several heterocycles such as thiophenes, furanes, benzothiophenes or benzofuranes. Among the 30 derivatives tested, the two derivatives 10 and 39 with Ki in the nanomolar range were identified (2.3 and 3 nM respectively). They exhibited a strict selectivity toward the alpha 4 beta 2 nicotinic receptor (up to 1 mu M) but interacted with the 5HT(3) receptors with Ki around 3 nM. Synthesis, SAR studies and a full description of the derivatives are reported. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.001

文献信息

• 1,4-DISUBSTITUTED 1,2,3-TRIAZOLES, METHODS FOR PREPARING SAME, AND DIAGNOSTIC AND THERAPEUTIC USES THEREOF
  申请人：Routier Sylvain

  公开号：US20140030191A1

  公开（公告）日：2014-01-30

  A compound having the following general formula (I): wherein: X is a nitrogen atom and Y is a carbon atom; or X is a carbon atom and Y is a nitrogen atom; the Ar group is an aryl or heteroaryl group; and the RN and RN′ groups, together with the carbon atoms to which they are bound, form a monocyclic or bicyclic azacycloalkane group. The pharmaceutically acceptable salts thereof, the hydrates or polymorphic crystalline structures thereof, and to the racemates, diastereoisomers, or enantiomers thereof are also described.

  具有以下通式（I）的化合物：其中：X是氮原子，Y是碳原子；或者X是碳原子，Y是氮原子；Ar基团是芳基或杂芳基；RN和RN′基团，与其所连接的碳原子一起，形成单环或双环氮杂环烷基团。还描述了其药学上可接受的盐、水合物或多晶型晶体结构，以及其消旋体、非对映异构体或对映异构体。
• 1,4-disubstituted 1,2,3-triazoles, methods for preparing same, and diagnostic and therapeutic uses thereof
  申请人：Routier Sylvain

  公开号：US10059704B2

  公开（公告）日：2018-08-28

  A compound having the following general formula (I): wherein: X is a nitrogen atom and Y is a carbon atom; or X is a carbon atom and Y is a nitrogen atom; the Ar group is an aryl or heteroaryl group; and the RN and RN′ groups, together with the carbon atoms to which they are bound, form a monocyclic or bicyclic azacycloalkane group. The pharmaceutically acceptable salts thereof, the hydrates or polymorphic crystalline structures thereof, and to the racemates, diastereoisomers, or enantiomers thereof are also described.

  具有以下通式(I)的化合物： 其中 X 是氮原子，Y 是碳原子；或 X 是碳原子，Y 是氮原子； Ar 基团是芳基或杂芳基；以及 RN和RN′基团与其结合的碳原子一起形成单环或双环偶氮环烷基团。还描述了其药学上可接受的盐、其水合物或多晶体结构，以及其外消旋体、非对映异构体或对映体。
• 1,2,3-TRIAZOLES 1,4-DISUBSTITUÉES, LEURS PROCÉDÉS DE PRÉPARATION ET LEURS UTILISATIONS DIAGNOSTIQUES ET THÉRAPEUTIQUES
  申请人：Centre National de la Recherche Scientifique (C.N.R.S.)

  公开号：EP2699570B1

  公开（公告）日：2018-08-22
• Design of α7 nicotinic acetylcholine receptor ligands using the (het)Aryl-1,2,3-triazole core: Synthesis, in vitro evaluation and SAR studies
  作者：Aziz Ouach、Frederic Pin、Emilie Bertrand、Johnny Vercouillie、Zuhal Gulhan、Céline Mothes、Jean-Bernard Deloye、Denis Guilloteau、Franck Suzenet、Sylvie Chalon、Sylvain Routier

  DOI：10.1016/j.ejmech.2015.11.001

  日期：2016.1

  We report here the synthesis of a large library of 1,2,3-triazole derivatives which were in vitro tested as alpha 7 nAchR ligands. The SAR study revealed that several crucial factors are involved in the affinity of these compounds for alpha 7 nAchR such as a (R) quinuclidine configuration and a mono C-3 quinuclidine substitution. The triazole ring was substituted by a phenyl ring bearing small OMe/CH2F groups or fluorine atom and by several heterocycles such as thiophenes, furanes, benzothiophenes or benzofuranes. Among the 30 derivatives tested, the two derivatives 10 and 39 with Ki in the nanomolar range were identified (2.3 and 3 nM respectively). They exhibited a strict selectivity toward the alpha 4 beta 2 nicotinic receptor (up to 1 mu M) but interacted with the 5HT(3) receptors with Ki around 3 nM. Synthesis, SAR studies and a full description of the derivatives are reported. (C) 2015 Elsevier Masson SAS. All rights reserved.