methyl 4”-(3-((2’-cyanobenzyl)thio)-5H-[1,2,4]triazino[5,6-b]indol-5-yl)-4’‘-oxobutanoate | 1428559-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 4”-(3-((2’-cyanobenzyl)thio)-5H-[1,2,4]triazino[5,6-b]indol-5-yl)-4’‘-oxobutanoate
• 英文别名: methyl 4'-(3-((2'-cyanobenzyl)thio)-5H-[1,2,4]triazino[5,6-b]indol-5-yl)-4'-oxobutanoate；methyl 4"-(3-((2'-cyanobenzyl)thio)-5H-[1,2,4]triazino[5,6-b]indol-5-yl)-4"-oxobutanoate；Methyl 4-[3-[(2-cyanophenyl)methylsulfanyl]-[1,2,4]triazino[5,6-b]indol-5-yl]-4-oxobutanoate；methyl 4-[3-[(2-cyanophenyl)methylsulfanyl]-[1,2,4]triazino[5,6-b]indol-5-yl]-4-oxobutanoate
• CAS: 1428559-12-9
• 化学式: C₂₂H₁₇N₅O₃S
• 分子量: 431.475
• InChiKey: LGVMMZRPBJAHAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  136
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5H-[1,2,4]噻嗪o[5,6-b]吲哚-3-硫醇 在 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 32.0h， 生成 methyl 4”-(3-((2’-cyanobenzyl)thio)-5H-[1,2,4]triazino[5,6-b]indol-5-yl)-4’‘-oxobutanoate
  参考文献：
  名称：

  Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists

  摘要：

  The cannabinoid receptor 2 (CB2R) has been linked with the regulation of inflammation, and selective receptor activation has been proposed as a target for the treatment of a range of inflammatory diseases such as atherosclerosis and arthritis. In order to identify selective CB2R agonists with appropriate physicochemical and ADME properties for future evaluation in vivo, we first performed a ligand-based virtual screen. Subsequent medicinal chemistry optimisation studies led to the identification of a new class of selective CB2R agonists. Several examples showed high levels of activity (EC50 < 200 nM) and binding affinity (K-i < 200 nM) for the CB2R, and no detectable activity at the CB1R. The most promising example, DIAS2, also showed favourable in vitro metabolic stability and absorption properties along with a clean selectivity profile when evaluated against a panel of GPCRs and kinases. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  DOI：

  10.1016/j.bmc.2014.11.002

文献信息

• [EN] CANNABINOID-2-RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RÉCEPTEUR DES CANNABINOÏDES 2
  申请人：ISIS INNOVATION

  公开号：WO2013041859A1

  公开（公告）日：2013-03-28

  The present invention relates to cannabinnoid-2-receptor (CB2R) agonist compounds. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them and to their use as therapeutic agents for the treatment and/or prevention of diseases or conditions in which CB2R stimulation is beneficial (especially inflammatory conditions).

  本发明涉及大麻素-2受体（CB2R）激动剂化合物。本发明还涉及制备这些化合物的方法、包含它们的药物组合物以及它们作为治疗剂用于治疗和/或预防CB2R刺激有益的疾病或状况（尤其是炎症条件）的使用。
• Cannabinoid-2-Receptor Agonists
  申请人：ISIS INNOVATION LIMITED

  公开号：US20140378451A1

  公开（公告）日：2014-12-25

  The present invention relates to cannabinoid-2-receptor (CB2R) agonist compounds. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them and to their use as therapeutic agents for the treatment and/or prevention of diseases or conditions in which CB2R stimulation is beneficial (especially inflammatory conditions).

  本发明涉及大麻素-2受体（CB2R）激动剂化合物。本发明还涉及这些化合物的制备过程，包括它们在内的药物组合物，以及它们作为治疗剂用于治疗和/或预防CB2R刺激有益的疾病或状况（尤其是炎症条件）的使用。
• CANNABINOID-2-RECEPTOR AGONISTS
  申请人：Isis Innovation Limited

  公开号：EP2766022A1

  公开（公告）日：2014-08-20
• Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists
  作者：Matteo Gianella-Borradori、Ivy Christou、Carole J.R. Bataille、Rebecca L. Cross、Graham M. Wynne、David R. Greaves、Angela J. Russell

  DOI：10.1016/j.bmc.2014.11.002

  日期：2015.1

  The cannabinoid receptor 2 (CB2R) has been linked with the regulation of inflammation, and selective receptor activation has been proposed as a target for the treatment of a range of inflammatory diseases such as atherosclerosis and arthritis. In order to identify selective CB2R agonists with appropriate physicochemical and ADME properties for future evaluation in vivo, we first performed a ligand-based virtual screen. Subsequent medicinal chemistry optimisation studies led to the identification of a new class of selective CB2R agonists. Several examples showed high levels of activity (EC50 < 200 nM) and binding affinity (K-i < 200 nM) for the CB2R, and no detectable activity at the CB1R. The most promising example, DIAS2, also showed favourable in vitro metabolic stability and absorption properties along with a clean selectivity profile when evaluated against a panel of GPCRs and kinases. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).