(2S)-2-[(2-Aminoethyl)amino]-3-(1-n-butyl-1H-imidazol-4-yl)propanoic acid | 400044-66-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-2-[(2-Aminoethyl)amino]-3-(1-n-butyl-1H-imidazol-4-yl)propanoic acid
• 英文别名: (S)-2-(2-aminoethylamino)-3-(1-butyl-1H-imidazol-4-yl)propanoic acid；(2S)-2-(2-aminoethylamino)-3-(1-butylimidazol-4-yl)propanoic acid
• CAS: 400044-66-8
• 化学式: C₁₂H₂₂N₄O₂
• 分子量: 254.332
• InChiKey: LLJMTPSWZYCMHR-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  93.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (7S)-6-{2-[(tert-butoxycarbonyl)amino]ethyl}-2-butyl-7-(methoxycarbonyl)-5-oxo-5,6,7,8-tetrahydroimidazo[1,5-c]pyrimidin-2-ium bromide 在 硫酸 作用下， 以 水 为溶剂， 反应 17.0h， 以82%的产率得到(2S)-2-[(2-Aminoethyl)amino]-3-(1-n-butyl-1H-imidazol-4-yl)propanoic acid
  参考文献：
  名称：

  Discovery of Potent & Selective Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor for the Treatment of Thrombosis

  摘要：

  Thrombin-activatable fibrinolysis inhibitor (TAFI) has emerged as a key link between the coagulation and fibrinolysis cascades and represents a promising new target for the treatment of thrombosis. A novel series of imidazolepropionic acids has been designed that exhibit high potency against activated TAFI (TAFIa) and excellent selectivity over plasma carboxypeptidase N (CPN). Structure activity relationships suggest that the imidazole moiety plays a key role in binding to the catalytic zinc of TAFIa, and this has been supported by crystallographic studies using porcine pancreatic carboxypeptidase B as a surrogate for TAFIa. The SAR program led to the identification of 21 (TAFIa Ki = 10 nM, selectivity TAFIa/CPN > 1000) as a candidate for clinical development. Compound 21 exhibited antithrombotic efficacy in a rabbit model of venous thrombosis, yet had no effect on surgical bleeding in the rabbit. In addition, 21 exhibited an excellent preclinical and clinical pharmacokinetic profile, characterized by paracellular absorption, low clearance, and a low volume of distribution, fully consistent with its physicochemical properties of low molecular weight (MW = 239) and high hydrophilicity (log D = -2.8). These data indicate 21 (UK-396,082) has potential as a novel TAFIa inhibitor for the treatment of thrombosis and other fibrin-dependent diseases in humans.

  DOI：

  10.1021/jm0702433

文献信息

• Pharmaceuticals
  申请人：——

  公开号：US20020147229A1

  公开（公告）日：2002-10-10

  The present invention provides compounds of formula (I) 1 as well as the use of such compounds in pharmaceutical compositions and methods of treatment. The compounds described herein represent a class of TAFIla inhibitors suitable for use in treating conditions such as thrombosis, atherosclerosis, adhesions, dermal scarring, cancer, fibrotic conditions, inflammatory diseases and those conditions which benefit from maintaining or enhancing bradykinin levels in the body.

  本发明提供了式(I)1的化合物，以及这些化合物在制药组合物和治疗方法中的应用。本文描述的化合物代表了一类适用于治疗血栓形成、动脉粥样硬化、粘连、皮肤瘢痕、癌症、纤维化疾病、炎症性疾病以及那些受益于维持或增强体内激肽酶激活因子Ⅰ（TAFIla）抑制剂的疾病的化合物。
• [EN] SUBSTITUTED IMIDAZOLES AS TAFIA INHIBITORS<br/>[FR] IMIDAZOLES SUBSTITUES UTILISES COMME INHIBITEURS TAFIA
  申请人：PFIZER LTD

  公开号：WO2002014285A1

  公开（公告）日：2002-02-21

  The present invention provides compounds of formula (I). These compounds are a class of TAFIa inhibitors, atherosclerosis, adhesions, dermal scarring, cancer, fibrotic conditions, inflammatory diseases and those conditions which benefit from maintaining or enhancing bradykinin levels in the body.

  本发明提供了化合物(I)的类别，这些化合物是一种TAFIa抑制剂，可用于治疗动脉粥样硬化、粘连、皮肤瘢痕、癌症、纤维化疾病、炎症性疾病以及那些需要维持或增强体内缓激肽水平的疾病。
• SUBSTITUTED IMIDAZOLES AS TAFIA INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1311488A1

  公开（公告）日：2003-05-21
• US6949577B2
  申请人：——

  公开号：US6949577B2

  公开（公告）日：2005-09-27
• [EN] STABILISED PHARMACEUTICAL COMPOSITIONS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES STABILISEES
  申请人：PFIZER LTD

  公开号：WO2005051384A1

  公开（公告）日：2005-06-09

  The present invention relates to the use of calcium carbonate as a stabilising agent in solid pharmaceutical compositions comprising an amino acid as the pharmaceutically active agent, to the stabilised pharmaceutical compositions resulting therefrom and processes for their preparation.