2-(3,4-Dimethoxyphenyl)-2-(1,4-dioxo-1,2,3,4-tetrahydrophthalazin-6-ylamino)acetic acid | 960232-00-2

• 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: 2-(3,4-Dimethoxyphenyl)-2-(1,4-dioxo-1,2,3,4-tetrahydrophthalazin-6-ylamino)acetic acid
• 英文别名: 2-(3,4-dimethoxyphenyl)-2-[(1,4-dioxo-2,3-dihydrophthalazin-6-yl)amino]acetic acid
• CAS: 960232-00-2
• 化学式: C₁₈H₁₇N₃O₆
• 分子量: 371.349
• InChiKey: HVVRYSWFKWZMDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(3,4-Dimethoxyphenyl)-2-(1,4-dioxo-1,2,3,4-tetrahydrophthalazin-6-ylamino)acetic acid 、 methyl N-(4-propan-2-ylsulfonyl-3-pyrrolidin-2-ylphenyl)carbamate 在 N-羟基-7-氮杂苯并三氮唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 3-(1-(2-(3,4-dimethoxyphenyl)-2-(1,4-dioxo-1,2,3,4-tetrahydrophthalazin-6-ylamino)acetyl)pyrrolidin-2-yl)-4-(isopropylsulfonyl)phenylcarbamate
  参考文献：
  名称：

  Discovery of Phenylglycine Lactams as Potent Neutral Factor VIIa Inhibitors

  摘要：

  Inhibitors of Factor Vila (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the Si binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the Si pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor. Optimization of this PI binding group led to the first series of neutral, permeable FVIIa inhibitors with low nanomolar potency.

  DOI：

  10.1021/acsmedchemlett.6b00282
• 作为产物：
  描述：

  4-氨基邻苯二甲酰肼 、 3,4-二甲氧基苯硼酸 、 乙醛酸 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 2-(3,4-Dimethoxyphenyl)-2-(1,4-dioxo-1,2,3,4-tetrahydrophthalazin-6-ylamino)acetic acid
  参考文献：
  名称：

  Discovery of Phenylglycine Lactams as Potent Neutral Factor VIIa Inhibitors

  摘要：

  Inhibitors of Factor Vila (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the Si binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the Si pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor. Optimization of this PI binding group led to the first series of neutral, permeable FVIIa inhibitors with low nanomolar potency.

  DOI：

  10.1021/acsmedchemlett.6b00282

文献信息

• BENZAMIDE FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS
  申请人：Priestley Eldon Scott

  公开号：US20100227894A1

  公开（公告）日：2010-09-09

  The present invention provides novel benzamide derivatives of Formula (I): or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the variables A, W, Y, Z, R 8 , and R 9 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.

  本发明提供了式(I)的新型苯甲酰胺衍生物：或其立体异构体、互变异构体、药学上可接受的盐、溶剂合物或前药，其中变量A、W、Y、Z、R8和R9如本文所定义。这些化合物是选择性因子VIIa的抑制剂，可用作药物。
• Benzamide factor VIIa inhibitors useful as anticoagulants
  申请人：Bristol-Myers Squibb Company

  公开号：US08222453B2

  公开（公告）日：2012-07-17

  The present invention provides novel benzamide derivatives of Formula (I): or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the variables A, W, Y, Z, R8, and R9 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.

  本发明提供一种新的苯甲酰胺衍生物，其化学式为(I)：或其立体异构体、互变异构体、药学上可接受的盐、溶剂化合物或前药，其中变量A、W、Y、Z、R8和R9如本文所定义。这些化合物是选择性因子VIIa抑制剂，可用作药物。
• 2-AMINOCARBONYLPHENYLAMINO-2-PHENILACETAMIDES AS FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2061756A2

  公开（公告）日：2009-05-27
• US8222453B2
  申请人：——

  公开号：US8222453B2

  公开（公告）日：2012-07-17
• [EN] BENZAMIDE FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS<br/>[FR] INHIBITEURS DE FACTEUR VIIA DE BENZAMIDE UTILES EN TANT QU'ANTICOAGULANTS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2007146719A2

  公开（公告）日：2007-12-21

  [EN] The present invention provides novel benzamide derivatives of Formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the variables A, W, Y, Z, R⁸, and R⁹ are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.
  [FR] La présente invention concerne de nouveaux dérivés de benzamide de formule (I) ou un stéréo-isomère, un tautomère, un sel pharmaceutiquement acceptable, un solvate ou un promédicament de ceux-ci, où les variables A, W, Y, Z, R⁸ et R⁹ sont comme présentement défini. Ces composés sont des inhibiteurs sélectifs de facteur VIIa qui peuvent être utilisés en tant que médicaments.