N,N-dimethyl-4-(6-(methylthio)-imidazo[1,2-a]pyridin-2-yl)benzenamine | 955376-42-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N,N-dimethyl-4-(6-(methylthio)-imidazo[1,2-a]pyridin-2-yl)benzenamine
• 英文别名: KP5TW22ME7；N,N-dimethyl-4-(6-methylsulfanylimidazo[1,2-a]pyridin-2-yl)aniline
• CAS: 955376-42-8
• 化学式: C₁₆H₁₇N₃S
• 分子量: 283.397
• InChiKey: WOYCDVDURLTMAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-(6-iodo-imidazo[1,2-a]pyridin-2-yl)-N,N-dimethylbenzenamine 、 sodium thiomethoxide 在 tris(dibenzylideneacetone)dipalladium (0) 、 1,1'-bis(diisopropylphosphino)ferrocene 三甲基氯化锡 作用下， 以 四氢呋喃 为溶剂， 120.0 ℃ 、2.07 MPa 条件下， 反应 0.17h， 以51%的产率得到N,N-dimethyl-4-(6-(methylthio)-imidazo[1,2-a]pyridin-2-yl)benzenamine
  参考文献：
  名称：

  Synthesis and Evaluation of N-Methyl and S-Methyl ¹¹C-Labeled 6-Methylthio-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridines as Radioligands for Imaging β-Amyloid Plaques in Alzheimer’s Disease

  摘要：

  6-Thiolato-substituted 2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridines (RS-IMPYs; 1-4) were synthesized as candidates for labeling with carbon-11 (t(1/2) = 20.4 min) and imaging of A(beta) plaques in living human brain using positron emission tomography (PET). K-i values for binding of these ligands to Alzheimer's disease brain homogenates were measured in vitro,against tritium-labeled 6 (Pittsburgh compound B). MeS-IMPY (3, K-i = 7.93 nM) was labeled with carbon-11 at its S- or N-methyl position to give [C-11]7 or [C-11]8, respectively. After injection into rats, [C-11]7 or [C-11]8 gave moderately high brain uptakes of radioactivity followed by rapid washout to low levels. The ratio of radioactivity at maximal uptake to that at 60 min reached 18.7 for [C-11]7. [C-11]7 behaved similarly in mouse and monkey. [C-11]7 also bound selectively to A(beta) plaques in post mortem human Alzheimer's disease brain. Although rapidly metabolized in rat by N-demethylation, [C-11]7 was stable in rat brain homogenates. The ex vivo brain radiometabolites observed in rats have a peripheral origin. Overall, [C-11]7 merits further evaluation in human subjects.

  DOI：

  10.1021/jm700970s

文献信息

• PET MONITORING OF AB-DIRECTED IMMUNOTHERAPY
  申请人：Janssen Alzheimer Immunotherapy

  公开号：EP2538982A1

  公开（公告）日：2013-01-02
• PET MONITORING OF A-BETA-DIRECTED IMMUNOTHERAPY
  申请人：Black Ronald

  公开号：US20130084245A1

  公开（公告）日：2013-04-04

  The present invention provides methods of monitoring Aβ-directed immunotherapy. The methods involve administering a PET ligand that binds to amyloid deposits and detecting the PET ligand in the brain to provide an indication of the level and/or distribution of amyloid deposits. Surprisingly, the data in the present application show that a statistically significant reduction in amyloid deposits occurs early and consistently among patients following initiation of treatment before statistically significant effects of most if not all other markers are detectable. In consequence, the present methods allow early detection of whether a patient is responding to the Aβ-directed immunotherapy and if necessary adjustment of the immunotherapy regime.
• US20140341812A1
  申请人：——

  公开号：US20140341812A1

  公开（公告）日：2014-11-20
• US8703096B2
  申请人：——

  公开号：US8703096B2

  公开（公告）日：2014-04-22
• [EN] PET MONITORING OF AB-DIRECTED IMMUNOTHERAPY<br/>[FR] SURVEILLANCE PET D'UNE IMMUNOTHÉRAPIE DIRIGÉE CONTRE L'A?
  申请人：WYETH LLC

  公开号：WO2011106732A1

  公开（公告）日：2011-09-01

  The present invention provides methods of monitoring Aβ-directed immunotherapy. The methods involve administering a PET ligand that binds to amyloid deposits and detecting the PET ligand in the brain to provide an indication of the level and/or distribution of amyloid deposits. Surprisingly, the data in the present application show that a statistically significant reduction in amyloid deposits occurs early and consistently among patients following initiation of treatment before statistically significant effects of most if not all other markers are detectable. In consequence, the present methods allow early detection of whether a patient is responding to the Aβ-directed immunotherapy and if necessary adjustment of the immunotherapy regime.