tert-butyl methyl(2-(methyl((6-nitro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)methyl)amino)ethyl)carbamate | 1613465-77-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: tert-butyl methyl(2-(methyl((6-nitro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)methyl)amino)ethyl)carbamate
• 英文别名: tert-butyl N-methyl (2-(methyl((6-nitro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)methyl)amino)ethyl)carbamate；Tert-butyl methyl(2-(methyl((6-nitro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)methyl)amino)ethyl)carbamate；tert-butyl N-methyl-N-[2-[methyl-[(6-nitro-4-oxo-3-phenylquinazolin-2-yl)methyl]amino]ethyl]carbamate
• CAS: 1613465-77-2
• 化学式: C₂₄H₂₉N₅O₅
• 分子量: 467.525
• InChiKey: HNUQQWXXOZMZTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl methyl(2-(methyl((6-nitro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)methyl)amino)ethyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 2-((methyl(2-(methylamino)ethyl)amino)methyl)-6-nitro-3-phenylquinazolin-4(3H)-one
  参考文献：
  名称：

  Development of (E)-2-((1,4-Dimethylpiperazin-2-ylidene)amino)-5-nitro-N-phenylbenzamide, ML336: Novel 2-Amidinophenylbenzamides as Potent Inhibitors of Venezuelan Equine Encephalitis Virus

  摘要：

  Venezuelan equine encephalitis virus (VEEV) is an emerging pathogenic alphavirus that can cause significant disease in humans. Given the absence of therapeutic options available and the significance of VEEV as a weaponized agent, an optimization effort was initiated around a quinazolinone screening hit 1 with promising cellular antiviral activity (EC50 = 0.8 mu M), limited cytotoxic liability (CC50 > 50 mu M), and modest in vitro efficacy in reducing viral progeny (63-fold at 5 mu M). Scaffold optimization revealed a novel rearrangement affording amidines, specifically compound 45, which was found to potently inhibit several VEEV strains in the low nanomolar range without cytotoxicity (EC50 = 0.02-0.04 mu M, CC50 > 50 mu M) while limiting in vitro viral replication (EC90 = 0.17 mu M). Brain exposure was observed in mice with 45. Significant protection was observed in VEEV-infected mice at 5 mg kg(-1) day(-1) and viral replication appeared to be inhibited through interference of viral nonstructural proteins.

  DOI：

  10.1021/jm501203v
• 作为产物：
  描述：

  2-(chloromethyl)-6-nitro-4H-benzo[d][1,3]oxazin-4-one 在 potassium carbonate 、 potassium iodide 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 0.33h， 生成 tert-butyl methyl(2-(methyl((6-nitro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)methyl)amino)ethyl)carbamate
  参考文献：
  名称：

  [EN] 6-SUBSTITUTED QUINAZOLINONE INHIBITORS
  [FR] INHIBITEURS DE QUINAZOLINONE 6-SUBSTITUÉS

  摘要：

  这项技术涉及到I-III式化合物和组合物，以及使用这些化合物的方法。本文描述的化合物和组合物可用于治疗或预防与阿尔法病毒相关的疾病，例如委内瑞拉马蹄病毒（VEEV）。

  公开号：

  WO2014093869A1

文献信息

• One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement
  作者：Chad E. Schroeder、Sarah A. Neuenswander、Tuanli Yao、Jeffrey Aubé、Jennifer E. Golden

  DOI：10.1039/c5ob02378e

  日期：——

  The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones is described. This methodology study explored reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core. The transformation was extensively optimized in terms of reaction conditions and scope, resulting

  描述了由喹唑啉酮的区域特异性重排产生的新型N-联苯甲idine的有效生成。该方法学研究探索了反应参数，包括变化的溶剂和温度的影响以及结构核心上变化的电子取代基。就反应条件和反应范围而言，对转化进行了广泛的优化，从而形成了始终如一地以高收率提供各种功能化am的方案。该方法可实现以前无法实现的区域结构衍生化，并且多步过程也简化为可伸缩的五步序列，可有效地从N中获得药理学上独特的（E）-苯甲酰胺基s-BOC保护的γ-和δ-氨基酸。
• 6-SUBSTITUTED QUINAZOLINONE INHIBITORS
  申请人：UNIVERSITY OF KANSAS

  公开号：US20150329499A1

  公开（公告）日：2015-11-19

  The present technology relates to compounds and compositions of Formulas I-III and methods using such compounds. The compounds and compositions described herein may be used in the treatment or prophylaxis of diseases associated with an alphavirus, for example, Venezuelan equine encephalitis virus (VEEV).

  本技术涉及公式I-III的化合物和组合物以及使用此类化合物的方法。此处描述的化合物和组合物可用于治疗或预防与阿尔法病毒相关的疾病，例如委内瑞拉马蹄热病毒（VEEV）。
• 6-substituted quinazolinone inhibitors
  申请人：University of Kansas

  公开号：US10087168B2

  公开（公告）日：2018-10-02

  The present technology relates to compounds and compositions of Formulas I-III and methods using such compounds. The compounds and compositions described herein may be used in the treatment or prophylaxis of diseases associated with an alphavirus, for example, Venezuelan equine encephalitis virus (VEEV).

  本技术涉及式 I-III 的化合物和组合物以及使用此类化合物的方法。本文所述的化合物和组合物可用于治疗或预防与α-病毒（例如委内瑞拉马脑炎病毒（VEEV））相关的疾病。
• US9580393B2
  申请人：——

  公开号：US9580393B2

  公开（公告）日：2017-02-28
• Development of (<i>E</i>)-2-((1,4-Dimethylpiperazin-2-ylidene)amino)-5-nitro-<i>N</i>-phenylbenzamide, ML336: Novel 2-Amidinophenylbenzamides as Potent Inhibitors of Venezuelan Equine Encephalitis Virus
  作者：Chad E. Schroeder、Tuanli Yao、Julie Sotsky、Robert A. Smith、Sudeshna Roy、Yong-Kyu Chu、Haixun Guo、Nichole A. Tower、James W. Noah、Sara McKellip、Melinda Sosa、Lynn Rasmussen、Layton H. Smith、E. Lucile White、Jeffrey Aubé、Colleen B. Jonsson、Donghoon Chung、Jennifer E. Golden

  DOI：10.1021/jm501203v

  日期：2014.10.23

  Venezuelan equine encephalitis virus (VEEV) is an emerging pathogenic alphavirus that can cause significant disease in humans. Given the absence of therapeutic options available and the significance of VEEV as a weaponized agent, an optimization effort was initiated around a quinazolinone screening hit 1 with promising cellular antiviral activity (EC50 = 0.8 mu M), limited cytotoxic liability (CC50 > 50 mu M), and modest in vitro efficacy in reducing viral progeny (63-fold at 5 mu M). Scaffold optimization revealed a novel rearrangement affording amidines, specifically compound 45, which was found to potently inhibit several VEEV strains in the low nanomolar range without cytotoxicity (EC50 = 0.02-0.04 mu M, CC50 > 50 mu M) while limiting in vitro viral replication (EC90 = 0.17 mu M). Brain exposure was observed in mice with 45. Significant protection was observed in VEEV-infected mice at 5 mg kg(-1) day(-1) and viral replication appeared to be inhibited through interference of viral nonstructural proteins.