1-benzyl-4-ethoxy-1,4lambda5-azaphosphinane 4-oxide | 1042425-92-2

• 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: 1-benzyl-4-ethoxy-1,4lambda5-azaphosphinane 4-oxide
• 英文别名: 1-benzyl-4-ethoxy-1,4-azaphosphinane 4-oxide；1-Benzyl-4-ethoxy-1,4-azaphosphinane 4-oxide；1-benzyl-4-ethoxy-1,4λ5-azaphosphinane 4-oxide
• CAS: 1042425-92-2
• 化学式: C₁₃H₂₀NO₂P
• 分子量: 253.281
• InChiKey: LRUWTESIKOAMDK-UHFFFAOYSA-N

物化性质

• 沸点：
  345.9±52.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-benzyl-4-ethoxy-1,4lambda5-azaphosphinane 4-oxide 在 palladium 10% on activated carbon 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 42.0h， 生成 4-ethoxy-1-(2-fluoro-4-nitro-phenyl)-[1,4]azaphosphinane 4-oxide
  参考文献：
  名称：

  WO2008/90570

  摘要：

  公开号：
• 作为产物：
  描述：

  ethyl divinylphosphinate 、 苄胺 以 乙醇 为溶剂， 反应 16.0h， 以79%的产率得到1-benzyl-4-ethoxy-1,4lambda5-azaphosphinane 4-oxide
  参考文献：
  名称：

  膦烷和氮杂膦烷是活化凝血酶激活纤溶抑制剂 (TAFIa) 的有效和选择性抑制剂

  摘要：

  活化凝血酶可激活纤溶抑制剂 (TAFIa) 的选择性和强效抑制剂有可能增加内源性和治疗性纤溶，并且像纤溶原药物一样发挥作用，而没有大出血的风险，因为它们不会干扰血小板活化或血液止血期间的凝血。因此，TAFIa抑制剂可用于高危患者中风、静脉血栓和肺栓塞的治疗、预防和二级预防。在本文中，我们描述了新型、有效、选择性膦烷和氮杂膦作为 TAFIa 抑制剂的设计、构效关系 (SAR) 和合成。几种高活性氮杂膦表现出有吸引力的特性，适合在血栓形成模型中进一步进行体内功效研究。

  DOI：

  10.1021/acs.jmedchem.0c02072

文献信息

• [EN] TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE<br/>[FR] INHIBITEURS TRICYCLIQUES DE POLY(ADP-RIBOSE)POLYMÉRASE
  申请人：NEWGEN THERAPEUTICS INC

  公开号：WO2012166983A1

  公开（公告）日：2012-12-06

  The invention provides for compositions comprising phosphorous containing tricyclic compounds, including phthalazin-l(2H)-one derivatives. The compounds are potent inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), particularly PARP-1 and potentially PARP-2. The also show good cellular activity in inhibiting poly(ADP- ribose) oligomer formation. The compounds may be useful as mono-therapy or in combination with other therapeutic agents in the treatment conditions where PARP is implicated, such as cancer, inflammatory diseases and ischemic conditions. Thus, also provided are methods for the treatment of a condition where PARP is implicated comprising administering to an effective amount of a compound of the invention to an individual in need thereof.

  该发明提供了包含含磷三环化合物的组合物，包括邻苯二氮杂吲哚酮衍生物。这些化合物是酶聚(腺苷二磷酸核糖)聚合酶（PARP）的有效抑制剂，特别是PARP-1和潜在的PARP-2。它们还显示出在抑制聚(腺苷二磷酸核糖)寡聚物形成方面具有良好的细胞活性。这些化合物可能在单独治疗或与其他治疗剂联合治疗PARP参与的疾病条件中发挥作用，如癌症、炎症性疾病和缺血性疾病。因此，还提供了一种治疗PARP参与的疾病条件的方法，包括向需要的个体施用该发明化合物的有效量。
• COMPOUNDS OF PHOSPHINANES AND AZAPHOSPHINANES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：LES LABORATOIRES SERVIER

  公开号：US20180016288A1

  公开（公告）日：2018-01-18

  Compounds of formula (I) wherein: Ak 1 represents an alkyl chain, X represents —(CH 2 ) m —, —CH(R)—, —N(R)—, —CH 2 —N(R)—, —N(R)—CH 2 — or —CH 2 —N(R)—CH 2 —, m and R are as defined in the description, R 1 and R 2 each represent H when X represents —(CH 2 ) m —, —CH(R)—, —N(R)—, —CH 2 —N(R)— or —N(R)—CH 2 —, or together form a bond when X represents —CH 2 —N(R)—CH 2 —, R 3 represents NH 2 , Cy-NH 2 , Cy-Ak 3 -NH 2 or piperidin-4-yl, Cy and Ak 3 are as defined in the description, R 4 and R 5 , which may be identical or different, each represent H or F, their optical isomers, and addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in treating conditions requiring a TAFIa inhibitor.

  式(I)的化合物中： Ak1代表一个烷基链， X代表—(CH2)m—，—CH(R)—，—N(R)—，— —N(R)—，—N(R)— —或— —N(R)— —， m和R如描述中所定义， R1和R2分别在X代表—( )m—，—CH(R)—，—N(R)—，— —N(R)—或—N(R)— —时代表H， 或者当X代表— —N(R)— —时，它们一起形成一个键， R3代表NH2，Cy-NH2，Cy-Ak3-NH2或哌啶-4-基， Cy和Ak3如描述中所定义， R4和R5，可能相同也可能不同，每个代表H或F， 它们的光学异构体， 以及它们与药学上可接受的酸形成的盐。 包含这些化合物的药品，在治疗需要TAFIa抑制剂的情况下有用。
• TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE
  申请人：NewGen Therapeutics, Inc.

  公开号：US20140221314A1

  公开（公告）日：2014-08-07

  The invention provides for compositions comprising phosphorous containing tricyclic compounds, including phthalazin-1(2H)-one derivatives. The compounds are potent inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), particularly PARP-1 and potentially PARP-2. The also show good cellular activity in inhibiting poly(ADP-ribose) oligomer formation. The compounds may be useful as mono-therapy or in combination with other therapeutic agents in the treatment conditions where PARP is implicated, such as cancer, inflammatory diseases and ischemic conditions. Thus, also provided are methods for the treatment of a condition where PARP is implicated comprising administering to an effective amount of a compound of the invention to an individual in need thereof.

  本发明提供了包含含磷三环化合物的组合物，包括邻苯二酮-1(2H)-酮衍生物。这些化合物是聚(ADP-核糖)聚合酶(PARP)的有效抑制剂，特别是PARP-1和潜在的PARP-2。它们还表现出良好的细胞活性，能够抑制聚(ADP-核糖)寡聚体形成。这些化合物可用作单一治疗或与其他治疗药物联合使用，治疗PARP参与的疾病，如癌症、炎症性疾病和缺血性疾病。因此，本发明还提供了一种治疗PARP参与的疾病的方法，包括向需要的个体施用本发明化合物的有效量。
• TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE) POLYMERASE
  申请人：Rakovina Therapeutics Inc.

  公开号：EP3925962A1

  公开（公告）日：2021-12-22

  The invention provides for compositions comprising phosphorous containing tricyclic compounds, including phthalazin-1(2H)-one derivatives. The compounds are potent inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), particularly PARP-1 and potentially PARP-2. The also show good cellular activity in inhibiting poly(ADP- ribose) oligomer formation. The compounds may be useful as mono-therapy or in combination with other therapeutic agents in the treatment conditions where PARP is implicated, such as cancer, inflammatory diseases and ischemic conditions. Thus, also provided are methods for the treatment of a condition where PARP is implicated comprising administering to an effective amount of a compound of the invention to an individual in need thereof.

  本发明提供了包含含磷三环化合物（包括酞嗪-1(2H)-酮衍生物）的组合物。这些化合物是聚（ADP-核糖）聚合酶（PARP）的强效抑制剂，尤其是 PARP-1，也可能是 PARP-2。这些化合物在抑制聚（ADP-核糖）寡聚体形成方面也显示出良好的细胞活性。在治疗与 PARP 有关的疾病（如癌症、炎症性疾病和缺血性疾病）时，这些化合物可作为单一疗法或与其他治疗剂联合使用。因此，还提供了治疗与 PARP 有关的病症的方法，包括向有需要的个体施用有效量的本发明化合物。
• Compounds of phosphinanes and azaphosphinanes, a process for their preparation and pharmaceutical compositions containing them
  申请人：LES LABORATOIRES SERVIER

  公开号：US10654878B2

  公开（公告）日：2020-05-19

  Compounds of formula (I) wherein: Ak1 represents an alkyl chain, X represents —(CH2)m—, —CH(R)—, —N(R)—, —CH2—N(R)—, —N(R)—CH2— or —CH2—N(R)—CH2—, m and R are as defined in the description, R1 and R2 each represent H when X represents —(CH2)m—, —CH(R)—, —N(R)—, —CH2—N(R)— or —N(R)—CH2—, or together form a bond when X represents —CH2—N(R)—CH2—, R3 represents NH2, Cy-NH2, Cy-Ak3-NH2 or piperidin-4-yl, Cy and Ak3 are as defined in the description, R4 and R5, which may be identical or different, each represent H or F, their optical isomers, and addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in treating conditions requiring a TAFIa inhibitor.

  式(I)化合物 其中 Ak1 代表烷基链、 X 代表-(CH2)m-、-CH(R)-、-N(R)-、- -N(R)-、-N(R)- -或- -N(R)- -、 m 和 R 如说明中所定义、 当 X 代表-( )m-、-CH(R)-、-N(R)-、- -N(R)-或-N(R)- -时，R1 和 R2 各自代表 H、 或当 X 代表- -N(R)- -时共同形成键、 R3 代表 NH2、Cy-NH2、Cy-Ak3-NH2 或哌啶-4-基、 Cy和Ak3如描述中所定义、 R4 和 R5 可以相同或不同，各自代表 H 或 F、 它们的光学异构体，以及它们与药学上可接受的酸的加成盐。 含有这些成分的医药产品可用于治疗需要 TAFIa 抑制剂的病症。