4-[2-(3,4-dimethoxybenzyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester | 944255-97-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-[2-(3,4-dimethoxybenzyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 4-[2-[(3,4-dimethoxyphenyl)methyl]-1,3-dioxoisoindol-4-yl]piperazine-1-carboxylate
• CAS: 944255-97-4
• 化学式: C₂₆H₃₁N₃O₆
• 分子量: 481.549
• InChiKey: ATZBVSXEINSRKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  88.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[2-(3,4-dimethoxybenzyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-[(3,4-Dimethoxyphenyl)methyl]-4-piperazin-1-ylisoindole-1,3-dione
  参考文献：
  名称：

  Nonpeptide Urotensin-II Receptor Antagonists: A New Ligand Class Based on Piperazino-Phthalimide and Piperazino-Isoindolinone Subunits

  摘要：

  We have discovered two related chemical series of nonpeptide urotensin-II (U-II) receptor antagonists based oil piperazino-phthalimide (5 and 6) and piperazino-isoindolinone (7) scaffolds. These structure types are distinctive from those of U-II receptor antagonist series reported in the literature. Antagonist 7a exhibited single-digit nanomolar potency in rat and human cell-based functional assays, as well as strong binding to the human U-II receptor. In advanced pharmacological testing, 7a blocked the effects of U-II in vitro in a rat aortic ring assay and in vivo in it rat ear-flush model. A discussion of U-II receptor antagonist pharmacophores is presented, and it specifically defined model is suggested from tricycle 13, which has it high degree of conformational constraint.

  DOI：

  10.1021/jm900683d
• 作为产物：
  描述：

  4-hydroxy-2-(3,4-dimethoxybenzyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl trifluoromethanesulfonic acid ester 、 N-Boc-哌嗪 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以61%的产率得到4-[2-(3,4-dimethoxybenzyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Nonpeptide Urotensin-II Receptor Antagonists: A New Ligand Class Based on Piperazino-Phthalimide and Piperazino-Isoindolinone Subunits

  摘要：

  We have discovered two related chemical series of nonpeptide urotensin-II (U-II) receptor antagonists based oil piperazino-phthalimide (5 and 6) and piperazino-isoindolinone (7) scaffolds. These structure types are distinctive from those of U-II receptor antagonist series reported in the literature. Antagonist 7a exhibited single-digit nanomolar potency in rat and human cell-based functional assays, as well as strong binding to the human U-II receptor. In advanced pharmacological testing, 7a blocked the effects of U-II in vitro in a rat aortic ring assay and in vivo in it rat ear-flush model. A discussion of U-II receptor antagonist pharmacophores is presented, and it specifically defined model is suggested from tricycle 13, which has it high degree of conformational constraint.

  DOI：

  10.1021/jm900683d

文献信息

• Urotensin II receptor antagonists
  申请人：Maryanoff E. Bruce

  公开号：US20070191391A1

  公开（公告）日：2007-08-16

  The invention is directed to Urotensin II antagonists. More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating Urotensin-II mediated disorders. Pharmaceutical and veterinary compositions and methods of treating cardiovascular disorders and various other disease states or conditions using compounds of the invention are also described.

  本发明涉及Urotensin II拮抗剂。更具体地，本发明涉及某些新颖的化合物，制备化合物的方法，组成物，中间体和衍生物以及治疗Urotensin-II介导的疾病的方法。还描述了使用本发明化合物的制药和兽医组合物以及治疗心血管疾病和各种其他疾病状态或病况的方法。
• UROTENSIN II RECEPTOR ANTAGONISTS
  申请人：Maryanoff Bruce E.

  公开号：US20110136824A1

  公开（公告）日：2011-06-09

  The invention is directed to Urotensin II antagonists. More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating Urotensin-II mediated disorders. Pharmaceutical and veterinary compositions and methods of treating cardiovascular disorders and various other disease states or conditions using compounds of the invention are also described.

  本发明涉及尿激肽II（Urotensin II）拮抗剂。更具体地说，本发明涉及某些新颖化合物，制备化合物的方法，组合物，中间体和其衍生物，以及治疗Urotensin-II介导的疾病的方法。还描述了使用本发明化合物的制药和兽医组合物以及治疗心血管疾病和各种其他疾病状态或病况的方法。
• WO2007/81995
  申请人：——

  公开号：——

  公开（公告）日：——
• US7915260B2
  申请人：——

  公开号：US7915260B2

  公开（公告）日：2011-03-29
• US8193191B2
  申请人：——

  公开号：US8193191B2

  公开（公告）日：2012-06-05