methyl 2-{1-[(benzyloxy)amino]-3-methoxy-1,3-dioxopropan-2-yl}benzoate | 1174225-91-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-{1-[(benzyloxy)amino]-3-methoxy-1,3-dioxopropan-2-yl}benzoate
• 英文别名: methyl 2-{1-[(benzyloxy)amino]-3-methoxy-1.3-dioxopropan-2-yl}benzoate；Methyl 2-[1-methoxy-1,3-dioxo-3-(phenylmethoxyamino)propan-2-yl]benzoate
• CAS: 1174225-91-2
• 化学式: C₁₉H₁₉NO₆
• 分子量: 357.363
• InChiKey: CUQPTLCQQLLWNR-UHFFFAOYSA-N

物化性质

• 密度：
  1.245±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-{1-[(benzyloxy)amino]-3-methoxy-1,3-dioxopropan-2-yl}benzoate 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 methyl 2-(benzyloxy)-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
  参考文献：
  名称：

  4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors

  摘要：

  A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at position 4 by carboxamido, chains was beneficial for antiviral activity since reproducible low micromolar anti-HIV activities were obtained for the first time within this scaffold.

  DOI：

  10.1021/ml400009t
• 作为产物：
  描述：

  邻羧基苯乙酸 在 N-甲基吗啉 、 正丁基锂 、 氯化亚砜 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 15.83h， 生成 methyl 2-{1-[(benzyloxy)amino]-3-methoxy-1,3-dioxopropan-2-yl}benzoate
  参考文献：
  名称：

  [EN] 2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONES AND RELATED COMPOUNDS USEFUL AS HIV REPLICATION INHIBITORS
  [FR] 2 -HYDROXYISOQUINOLINE- 1, 3 ( 2H, 4H) - DIONES ET COMPOSÉS ASSOCIÉS SERVANT D'INHIBITEURS DE LA RÉPLICATION DU VIH

  摘要：

  本发明涉及作为HIV整合酶抑制剂的化合物和组合物。该发明的化合物为式(I)的化合物，或其互变异构体(I')，或所述化合物或其互变异构体的药用可接受盐或溶剂，其中R1、R2、R3、R4、R5和R6具有定义的含义。

  公开号：

  WO2012085003A1

文献信息

• Facile synthesis of 4-alkoxycarbonylisoquinoline-1,3-diones and 5-alkoxycarbonyl-2-benzazepine-1,3-diones<i>via</i>a mild alkaline cyclization
  作者：Muriel Billamboz、Fabrice Bailly、Philippe Cotelle

  DOI：10.1002/jhet.52

  日期：2009.5

  A series of 4-methoxycarbonylisoquinoline-1,3-diones was obtained from homophthalic acid in four steps. The key step was the quantitative and rapid alkaline cyclization of 2-methoxycarbonyl-2-(2-methoxycarbonylphenyl) acetamides. Homologation easily afforded in the same conditions 5-carboxy-2-benzazepine-1,3-dione. J. Heterocyclic Chem., 46, 392 (2009).

  一系列4-甲氧基羰基异喹啉-1,3-二酮从 高邻苯二甲酸分为四个步骤。关键步骤是2-甲氧基羰基-2-（2-甲氧基羰基苯基）乙酰胺的定量和快速碱性环化。在相同条件下很容易获得同源性5-羧基-2-苯并ze庚因-1,3-二酮。J. Heterocyclic Chem。，46，392（2009）。
• [EN] 2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONES AND RELATED COMPOUNDS USEFUL AS HIV REPLICATION INHIBITORS<br/>[FR] 2 -HYDROXYISOQUINOLINE- 1, 3 ( 2H, 4H) - DIONES ET COMPOSÉS ASSOCIÉS SERVANT D'INHIBITEURS DE LA RÉPLICATION DU VIH
  申请人：UNIV LEUVEN KATH

  公开号：WO2012085003A1

  公开（公告）日：2012-06-28

  The present invention relates to compounds and compositions acting as inhibitors of HIV integrase. The compound of the invention is of Formula (I), or a tautomer (I') thereof, or a pharmaceutically acceptable salt, or solvate of said compound or tautomer thereof, wherein R1, R2, R3, R4, R5 and R6 have defined meanings.

  本发明涉及作为HIV整合酶抑制剂的化合物和组合物。该发明的化合物为式(I)的化合物，或其互变异构体(I')，或所述化合物或其互变异构体的药用可接受盐或溶剂，其中R1、R2、R3、R4、R5和R6具有定义的含义。
• 4-Substituted 2-Hydroxyisoquinoline-1,3(2<i>H</i>,4<i>H</i>)-diones as a Novel Class of HIV-1 Integrase Inhibitors
  作者：Muriel Billamboz、Virginie Suchaud、Fabrice Bailly、Cedric Lion、Jonas Demeulemeester、Christina Calmels、Marie-Line Andréola、Frauke Christ、Zeger Debyser、Philippe Cotelle

  DOI：10.1021/ml400009t

  日期：2013.7.11

  A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at position 4 by carboxamido, chains was beneficial for antiviral activity since reproducible low micromolar anti-HIV activities were obtained for the first time within this scaffold.