3-((2-amino-3-pentylquinolin-5-yl)methyl)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-((2-amino-3-pentylquinolin-5-yl)methyl)benzamide
• 英文别名: 3-[(2-Amino-3-pentylquinolin-5-yl)methyl]benzamide；3-[(2-amino-3-pentylquinolin-5-yl)methyl]benzamide
• 化学式: C₂₂H₂₅N₃O
• 分子量: 347.46
• InChiKey: AFHVJGVQTUATRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  正庚腈 在 四(三苯基膦)钯 、 potassium tert-butylate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 二甲基亚砜 、 叔丁醇 为溶剂， 反应 23.0h， 生成 3-((2-amino-3-pentylquinolin-5-yl)methyl)benzamide
  参考文献：
  名称：

  Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity

  摘要：

  Human Toll-like receptor 8 (hTLR8) is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Crystal structures of the ectodomain of hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8. We hypothesized that the potency of a previously reported best-in-class pure TLR8 agonist, 3-pentylquinoline-2amine, could be further enhanced by "designing in" functional groups that would mimic key intermolecular interactions that we had observed in the crystal structures. We performed a focused exploration of decorating the quinoline core with alkylamino groups at all possible positions. These studies have led to the identification of a novel TLR8 agonist that was similar to 20-fold more potent than the parent compound and displays prominent adjuvantic activity in a rabbit model of immunization.

  DOI：

  10.1021/acs.jmedchem.5b01087

文献信息

• Human TLR8-selective agonists
  申请人：UNIVERSITY OF KANSAS

  公开号：US11130736B2

  公开（公告）日：2021-09-28

  The disclosure provides human toll-like receptor modulators of general Formula (II), wherein R1, R2, R3, R4, R5, R6, R7, R8 are defined herein.

  本公开提供通式（II）的人类收费样受体调节剂，其中 R1、R2、R3、R4、R5、R6、R7、R8 在本文中定义。
• QUINOLINE-2-AMINE DERIVATIVES AS HUMAN TLR8-SELECTIVE AGONISTS FOR INCREASING IMMUNE RESPONSE
  申请人：The University of Kansas

  公开号：EP3337481B1

  公开（公告）日：2020-11-11
• HUMAN TLR8-SELECTIVE AGONISTS
  申请人：The University of Kansas

  公开号：EP3337481A1

  公开（公告）日：2018-06-27
• [EN] HUMAN TLR8-SELECTIVE AGONISTS<br/>[FR] AGONISTES DE SÉLECTION DE TLR8 HUMAINS
  申请人：UNIV KANSAS

  公开号：WO2017034986A1

  公开（公告）日：2017-03-02

  The disclosure provides human toll-like receptor modulators of general Formula (II), wherein R1, R2, R3, R4, R5, R6, R7, R8 are defined herein.
• Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity
  作者：Mallesh Beesu、Giuseppe Caruso、Alex C. D. Salyer、Karishma K. Khetani、Diptesh Sil、Mihiri Weerasinghe、Hiromi Tanji、Umeharu Ohto、Toshiyuki Shimizu、Sunil A. David

  DOI：10.1021/acs.jmedchem.5b01087

  日期：2015.10.8

  Human Toll-like receptor 8 (hTLR8) is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Crystal structures of the ectodomain of hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8. We hypothesized that the potency of a previously reported best-in-class pure TLR8 agonist, 3-pentylquinoline-2amine, could be further enhanced by "designing in" functional groups that would mimic key intermolecular interactions that we had observed in the crystal structures. We performed a focused exploration of decorating the quinoline core with alkylamino groups at all possible positions. These studies have led to the identification of a novel TLR8 agonist that was similar to 20-fold more potent than the parent compound and displays prominent adjuvantic activity in a rabbit model of immunization.