tert-butyl N-(8-formyl-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate | 1147077-80-2

• 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-formyl-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
• CAS: 1147077-80-2
• 化学式: C₂₈H₂₇N₃O₆
• 分子量: 501.539
• InChiKey: YPTVGPZXXUCICF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl N-(8-formyl-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate 在 potassium permanganate 作用下， 以 水 、 丙酮 为溶剂， 反应 14.0h， 以57%的产率得到2-((bis-tert-butoxycarbonyl)amino)-5-oxo-4-phenyl-5H-indeno[1,2-d]pyrimidine-8-carboxylic acid
  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：

  tert-butyl N-(8-methyl-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate 在 N-溴代丁二酰亚胺(NBS) 、 邻苯二甲酸二丁酯 、 N-甲基吗啉氧化物 作用下， 以 乙腈 、 苯 为溶剂， 反应 18.0h， 生成 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：

  Design and Characterization of Optimized Adenosine A_2A/A₁ Receptor Antagonists for the Treatment of Parkinson's Disease

  摘要：

  The design and characterization of two, dual adenosine A(2A)/A(1) receptor antagonists in several animal models of Parkinson's disease is described. Compound 1 was previously reported as a potential treatment for Parkinson's disease. Further characterization of 1 revealed that it was metabolized to reactive intermediates that caused the genotoxicity of 1 in the Ames and mouse lymphoma L51784 assays. The identification of the metabolites enabled the preparation of two optimized compounds 13 and 14 that were devoid of the metabolic liabilities associated with 1. Compounds 13 and 14 are potent dual A(2A)/A(1) receptor antagonists that have 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 and rat models of reserpine-induced akinesia, and the rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation.

  DOI：

  10.1021/jm201640m

文献信息

• ARYLINDENOPYRIMIDINES COMPOUND AND USE AS AN ADENOSINE A2a RECEPTOR ANTAGONISTS
  申请人：SHOOK Brian C.

  公开号：US20090111827A1

  公开（公告）日：2009-04-30

  This invention relates to a novel arylindenopyrimidine, A, and its therapeutic and prophylactic uses. Disorders treated and/or prevented include Parkinson's Disease.

  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。
• 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.
• US8017614B2
  申请人：——

  公开号：US8017614B2

  公开（公告）日：2011-09-13
• [EN] ARYLINDENOPYRIMIDINES AND THEIR USE AS ADENOSINE A2A RECEPTOR ANTAGONISTS<br/>[FR] ARYLINDÉNOPYRIMIDINES ET LEUR UTILISATION COMME ANTAGONISTES DES RÉCEPTEURS A2A DE L'ADÉNOSINE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2009055308A1

  公开（公告）日：2009-04-30

  This invention relates to a novel arylindenopyrimidine, A, and its therapeutic and prophylactic uses as an antagonist of Adenosine A2a receptors. Disorders treated ans/or prevented include Parkinson's Disease.
• Design and Characterization of Optimized Adenosine A_2A/A₁ Receptor Antagonists for the Treatment of Parkinson's Disease
  作者：Brian C. Shook、Stefanie Rassnick、Nathaniel Wallace、Jeffrey Crooke、Mark Ault、Devraj Chakravarty、J. Kent Barbay、Aihua Wang、Mark T. Powell、Kristi Leonard、Vernon Alford、Robert H. Scannevin、Karen Carroll、Lisa Lampron、Lori Westover、Heng-Keang Lim、Ronald Russell、Shawn Branum、Kenneth M. Wells、Sandra Damon、Scott Youells、Xun Li、Derek A. Beauchamp、Kenneth Rhodes、Paul F. Jackson

  DOI：10.1021/jm201640m

  日期：2012.2.9

  The design and characterization of two, dual adenosine A(2A)/A(1) receptor antagonists in several animal models of Parkinson's disease is described. Compound 1 was previously reported as a potential treatment for Parkinson's disease. Further characterization of 1 revealed that it was metabolized to reactive intermediates that caused the genotoxicity of 1 in the Ames and mouse lymphoma L51784 assays. The identification of the metabolites enabled the preparation of two optimized compounds 13 and 14 that were devoid of the metabolic liabilities associated with 1. Compounds 13 and 14 are potent dual A(2A)/A(1) receptor antagonists that have 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 and rat models of reserpine-induced akinesia, and the rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation.