(R)-2-(N-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methoxy-phenylsulfonamido)-N-hydroxy-3-methylbutanamide | 1378929-11-3

• 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: (R)-2-(N-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methoxy-phenylsulfonamido)-N-hydroxy-3-methylbutanamide
• 英文别名: (2R)-2-[[1-(2-fluoroethyl)triazol-4-yl]methyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-methylbutanamide
• CAS: 1378929-11-3
• 化学式: C₁₇H₂₄FN₅O₅S
• 分子量: 429.472
• InChiKey: LOPZANGJCBIBLO-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (R)-tert-butyl 2-(4-methoxyphenylsulfonamido-N-(prop-2-yn-1-yl))-3-methylbutanoate 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 (R)-2-(N-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methoxy-phenylsulfonamido)-N-hydroxy-3-methylbutanamide
  参考文献：
  名称：

  [EN] COMPOUNDS WITH MATRIX-METALLOPROTEINASE INHIBITORY ACTIVITY
  [FR] COMPOSÉS AVEC ACTIVITÉ INHIBITRICE DE MÉTALLOPROTÉINASE DE MATRICE

  摘要：

  本发明涉及治疗和诊断试剂领域，更具体地涉及一种具有式（I）的化合物，该化合物是基质金属蛋白酶（MMPs）的抑制剂，并且在治疗与之相关的疾病如心血管疾病、炎症性疾病和恶性疾病方面有用。本发明的一个实施例是一种带有18-氟原子的式（I）化合物，具有适用于诊断成像的基质金属蛋白酶抑制活性。本发明还公开了一种包含本发明的基质金属蛋白酶（MMPs）抑制剂或相应标记化合物的制药组合物，适合于哺乳动物管理。此外，本发明还公开了在合成本发明的基质金属蛋白酶（MMPs）抑制剂和诊断成像剂中的中间体。

  公开号：

  WO2013010573A1

文献信息

• [EN] COMPOUNDS WITH MATRIX-METALLOPROTEINASE INHIBITORY ACTIVITY<br/>[FR] COMPOSÉS AVEC ACTIVITÉ INHIBITRICE DE MÉTALLOPROTÉINASE DE MATRICE
  申请人：UNIV MUENSTER

  公开号：WO2013010573A1

  公开（公告）日：2013-01-24

  The present invention relates to the field of therapeutic and diagnostic agents and more specifically to compounds of formula (I) that are inhibitors of matrix-metalloproteinases (MMPs) and are useful in the treatment of diseases related thereto such as cardiovascular diseases, inflammatory diseases and malignant diseases. One embodiment of the invention is a compound of formula (I) labeled with a 18-fluorine atom having matrix metalloproteinase inhibitory activity suitable for diagnostic imaging. Also disclosed in the present invention is a pharmaceutical composition comprising the inhibitors of matrix-metalloproteinases (MMPs) of the invention or the corresponding labeled compounds useful as diagnostic imaging agents of the invention in a form suitable for mammalian administration. The invention furthermore discloses intermediates in the synthesis of the inhibitors of matrix-metalloproteinases (MMPs) of the invention and of the diagnostic imaging agents of the invention.

  本发明涉及治疗和诊断试剂领域，更具体地涉及一种具有式（I）的化合物，该化合物是基质金属蛋白酶（MMPs）的抑制剂，并且在治疗与之相关的疾病如心血管疾病、炎症性疾病和恶性疾病方面有用。本发明的一个实施例是一种带有18-氟原子的式（I）化合物，具有适用于诊断成像的基质金属蛋白酶抑制活性。本发明还公开了一种包含本发明的基质金属蛋白酶（MMPs）抑制剂或相应标记化合物的制药组合物，适合于哺乳动物管理。此外，本发明还公开了在合成本发明的基质金属蛋白酶（MMPs）抑制剂和诊断成像剂中的中间体。
• Compounds with matrix-metalloproteinase inhibitory activity and imaging agents thereof
  申请人：Westfälische Wilhelms-Universität Münster

  公开号：EP2644601A1

  公开（公告）日：2013-10-02

  The present invention relates to the field of therapeutic, diagnostic and imaging agents and more specifically to compounds having the following general formula. The compounds are inhibitors of matrix-metalloproteinases (MMPs).

  本发明涉及治疗、诊断和成像剂领域，更具体地涉及具有以下一般式的化合物。这些化合物是基质金属蛋白酶（MMPs）的抑制剂。
• Compounds With Matrix-Metalloproteinase Inhibitory Activity and Imaging Agents Thereof
  申请人：Chen Gang

  公开号：US20130217887A1

  公开（公告）日：2013-08-22

  Novel compounds and pharmaceutical compositions having MMP inhibitory activity are disclosed, which have been found to be particularly useful in the prevention, treatment and diagnostic imaging of diseases associated with an unpaired activity of MMP, amongst others MMP-2, MMP-8, MMP-9 and/or MMP-13 to name a few. The compounds of the present invention are useful for the prevention, the treatment and the in vivo diagnostic imaging of a range of disease states (inflammatory, malignant and degenerative diseases) where specific matrix metalloproteinases are known to be involved.
• US9023318B2
  申请人：——

  公开号：US9023318B2

  公开（公告）日：2015-05-05
• A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation
  作者：Verena Hugenberg、Hans-Jörg Breyholz、Burkhard Riemann、Sven Hermann、Otmar Schober、Michael Schäfers、Umesh Gangadharmath、Vani Mocharla、Hartmuth Kolb、Joseph Walsh、Wei Zhang、Klaus Kopka、Stefan Wagner

  DOI：10.1021/jm300199g

  日期：2012.5.24

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.