tert-butyl N-[8-(bromomethyl)-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate | 1147077-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: tert-butyl N-[8-(bromomethyl)-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
• CAS: 1147077-78-8
• 化学式: C₂₈H₂₈BrN₃O₅
• 分子量: 566.451
• InChiKey: CFXFYQASDVFPAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  98.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[8-(bromomethyl)-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate 在 N-甲基吗啉氧化物 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以68%的产率得到tert-butyl N-(8-formyl-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
  参考文献：
  名称：

  ARYLINDENOPYRIMIDINES COMPOUND AND USE AS AN ADENOSINE A2a RECEPTOR ANTAGONISTS

  摘要：

  这项发明涉及一种新型芳基吲哚吡啶类化合物A及其治疗和预防用途。治疗和/或预防的疾病包括帕金森病。

  公开号：

  US20090111827A1
• 作为产物：
  描述：

  2-amino-8-methyl-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one 在 4-二甲氨基吡啶 、 过氧化苯甲酰 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 作用下， 以 乙酸乙酯 、 苯 为溶剂， 反应 34.0h， 生成 tert-butyl N-[8-(bromomethyl)-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
  参考文献：
  名称：

  [EN] ARYLINDENOPYRIMIDINES FOR TREATING NEURODEGENERATIVE AND MOVEMENT DISORDERS WHILE MINIMIZING CARDIAC TOXICITY
  [FR] ARYLINDENOPYRIMIDINES POUR TRAITER LES TROUBLES NEURODÉGÉNÉRATIFS ET LES TROUBLES DU MOUVEMENT TOUT EN LIMITANT LA TOXICITÉ CARDIAQUE

  摘要：

  这项发明提供了化合物的新型芳基吲哚吡咯并吡嘧啶（Formula (I)）以及包含这些化合物的药物组合物，用于治疗通过拮抗腺苷A1和/或A2a受体而改善的疾病。该发明还提供了使用这种药物组合物的治疗和预防方法。

  公开号：

  WO2011159302A1

文献信息

• ARYLINDENOPYRIMIDINES WITH REDUCED hERG CHANNEL BINDING
  申请人：JACKSON Paul

  公开号：US20110312956A1

  公开（公告）日：2011-12-22

  This invention provides novel arylindenopyrimidines of the Formula (I), and pharmaceutical compositions comprising same, useful for treating disorders ameliorated by antagonizing adenosine A1 and/or A2a receptors. This invention also provides therapeutic and prophylactic methods using the instant pharmaceutical compositions.

  这项发明提供了化合物的新颖芳基吲哚吡咯啉酮类化合物（式（I）），以及包含这些化合物的药物组合物，用于治疗通过拮抗腺苷A1和/或A2a受体而改善的疾病。该发明还提供了使用这种药物组合物进行治疗和预防的方法。
• ARYLINDENOPYRIMIDINES AND THEIR USE AS ADENOSINE A2a
  申请人：SHOOK Brian C.

  公开号：US20090111804A1

  公开（公告）日：2009-04-30

  This invention relates to novel arylindenopyrimidines A, B, and C, and their therapeutic and prophylactic uses. Disorders treated and/or prevented using these compounds include Parkinson's Disease.

  这项发明涉及新型芳基茚并嘧啶类化合物A、B和C，以及它们的治疗和预防用途。使用这些化合物治疗和/或预防的疾病包括帕金森病。
• Optimization of arylindenopyrimidines as potent adenosine A2A/A1 antagonists
  作者：Brian C. Shook、Stefanie Rassnick、Devraj Chakravarty、Nathaniel Wallace、Mark Ault、Jeffrey Crooke、J. Kent Barbay、Aihua Wang、Kristi Leonard、Mark T. Powell、Vernon Alford、Daniel Hall、Kenneth C. Rupert、Geoffrey R. Heintzelman、Kristen Hansen、James L. Bullington、Robert H. Scannevin、Karen Carroll、Lisa Lampron、Lori Westover、Ronald Russell、Shawn Branum、Kenneth Wells、Sandra Damon、Scott Youells、Derek Beauchamp、Xun Li、Kenneth Rhodes、Paul F. Jackson

  DOI：10.1016/j.bmcl.2010.03.024

  日期：2010.5

  Two reactive metabolites were identified in vivo for the dual A(2A)/A(1) receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro and in vivo activity. (C) 2010 Elsevier Ltd. All rights reserved.
• Methylene amine substituted arylindenopyrimidines as potent adenosine A2A/A1 antagonists
  作者：Brian C. Shook、Stefanie Rassnick、Daniel Hall、Kenneth C. Rupert、Geoffrey R. Heintzelman、Kristen Hansen、Devraj Chakravarty、James L. Bullington、Robert H. Scannevin、Brian Magliaro、Lori Westover、Karen Carroll、Lisa Lampron、Ronald Russell、Shawn Branum、Kenneth Wells、Sandra Damon、Scott Youells、Xun Li、Mel Osbourne、Keith Demarest、Yuting Tang、Kenneth Rhodes、Paul F. Jackson

  DOI：10.1016/j.bmcl.2010.03.042

  日期：2010.5

  A novel series of arylindenopyrimidines were identified as A(2A) and A(1) receptor antagonists. The series was optimized for in vitro activity by substituting the 8- and 9-positions with methylene amine substituents. The compounds show excellent activity in mouse models of Parkinson's disease when dosed orally. (C) 2010 Elsevier Ltd. All rights reserved.
• In Vivo Characterization of a Dual Adenosine A_2A/A₁ Receptor Antagonist in Animal Models of Parkinson’s Disease
  作者：Brian C. Shook、Stefanie Rassnick、Melville C. Osborne、Scott Davis、Lori Westover、Jamie Boulet、Daniel Hall、Kenneth C. Rupert、Geoffrey R. Heintzelman、Kristin Hansen、Devraj Chakravarty、James L. Bullington、Ronald Russell、Shawn Branum、Kenneth M. Wells、Sandra Damon、Scott Youells、Xun Li、Derek A. Beauchamp、David Palmer、Mayra Reyes、Keith Demarest、Yuting Tang、Kenneth Rhodes、Paul F. Jackson

  DOI：10.1021/jm100971t

  日期：2010.11.25

  The in vivo characterization of a dual adenosine A(2A)/A(1) I receptor antagonist in several animal models of Parkinson's disease is described. Discovery and scale-up syntheses of compound 1 are described in detail, highlighting optimization steps that increased the overall yield of I from 10.0% to 30.5%. Compound 1 is a potent A(2A)/A(1) receptor antagonist in vitro (A(2A) K-i = 4.1 nM A(1) K-i = 17.0 nM) that has excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse model of reserpine-induced akinesia, rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation, and MPTP-treated non-human primate model.