N4,N6-双(4-氟-3-甲基苄基)嘧啶-4,6-二甲酰胺 | 544678-85-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: N4,N6-双(4-氟-3-甲基苄基)嘧啶-4,6-二甲酰胺
• 中文别名: MMP-13抑制剂
• 英文名称: pyrimidine-4,6-dicarboxylic acid bis(4-fluoro-3-methyl-benzylamide)
• 英文别名: DB04760；N4,N6-Bis(4-fluoro-3-methylbenzyl)pyrimidine-4,6-dicarboxamide；4-N,6-N-bis[(4-fluoro-3-methylphenyl)methyl]pyrimidine-4,6-dicarboxamide
• CAS: 544678-85-5
• 化学式: C₂₂H₂₀F₂N₄O₂
• 分子量: 410.423
• InChiKey: PYFRREJCFXFNRR-UHFFFAOYSA-N

物化性质

• 沸点：
  684.6±55.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)
• 溶解度：
  乙醇中≤0.5mg/ml；DMSO 中≤2mg/ml；二甲基甲酰胺中≤2mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  84
• 氢给体数：
  2
• 氢受体数：
  6

制备方法与用途

生物活性

DB04760（化合物4）是一种有效的、高选择性的非锌螯合的MMP-13抑制剂，其IC50值为8 nM。DB04760显著降低了紫杉醇的神经毒性，并具有抗癌活性。

靶点

MMP-13
8 nM (IC50)

反应信息

• 作为产物：
  描述：

  4-氟-3-甲基苄胺 、 嘧啶-4,6-二甲酸二甲酯 在 氮气 、 乙醚 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以to give 0.42 grams (87%) of Pyrimidine-4,6-dicarboxylic acid bis-(4-fluoro-3-methyl-benzylamide) (51) as a white crystal solid的产率得到N4,N6-双(4-氟-3-甲基苄基)嘧啶-4,6-二甲酰胺
  参考文献：
  名称：

  MATRIX METALLOPROTEINASE INHIBITORS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISEASES

  摘要：

  本发明一般涉及含有MMP抑制化合物的双酰胺，更具体地涉及具有选择性氘代的双酰胺MMP-13抑制剂，其相对于当前已知的MMP-13抑制剂表现出增强的稳定性或效力。此外，本发明还涉及一种治疗患者疼痛和炎症的方法，包括向患者施用本化合物的减痛有效量。

  公开号：

  US20150274702A1

文献信息

• [EN] MATRIX METALLOPROTEINASE INHIBITORS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISEASES<br/>[FR] INHIBITEURS DE MÉTALLOPROTÉINASES MATRICIELLES ET MÉTHODES DE TRAITEMENT DE LA DOULEUR ET D'AUTRES MALADIES
  申请人：AQUILUS PHARMACEUTICALS INC

  公开号：WO2014062204A1

  公开（公告）日：2014-04-24

  The present invention relates generally to bis-amide containing MMP inhibiting compounds, and more particularly to selectively deuterated bis-amide MMP-13 inhibiting compounds that exhibit increased stability or potency in relation to currently known MMP-13 inhibitors. Additionally, the present invention relates to methods for treating pain and inflammation in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明一般涉及含有MMP抑制化合物的双酰胺，更具体地涉及选择性氘代双酰胺MMP-13抑制化合物，该化合物相对于目前已知的MMP-13抑制剂具有增加的稳定性或效力。此外，本发明还涉及一种治疗病人疼痛和炎症的方法，包括向病人施用一种现有化合物的减痛有效量。
• MATRIX METALLOPROTEINASE INHIBITORS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISEASES
  申请人：SUCHOLEIKI Irving

  公开号：US20150274702A1

  公开（公告）日：2015-10-01

  The present invention relates generally to bis-amide containing MMP inhibiting compounds, and more particularly to selectively deuterated bis-amide MMP-13 inhibiting compounds that exhibit increased stability or potency in relation to currently known MMP-13 inhibitors. Additionally, the present invention relates to methods for treating pain and inflammation in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明一般涉及含有MMP抑制化合物的双酰胺，更具体地涉及具有选择性氘代的双酰胺MMP-13抑制剂，其相对于当前已知的MMP-13抑制剂表现出增强的稳定性或效力。此外，本发明还涉及一种治疗患者疼痛和炎症的方法，包括向患者施用本化合物的减痛有效量。
• Treatment of age-related macular degeneration and other eye diseases with apolipoprotein mimetics
  申请人：MacRegen, Inc.

  公开号：US10426817B2

  公开（公告）日：2019-10-01

  The present disclosure provides apolipoprotein (apo) mimetics useful for the treatment of age-related macular degeneration (AMD) and other eye disorders. The apo mimetics can be peptides/polypeptides that mimic, e.g., the lipid-clearing action of apolipoproteins such as apoA-I and apoE. The apo mimetics can exert other beneficial effects, such as reduction of inflammation, oxidative stress and neovascularization. The apo mimetics can be used to treat any stages (including the early, intermediate and advance stages) of AMD, and any phenotypes of AMD, including geographic atrophy (GA) (including non-central GA and central GA) and neovascularization (NV) (including types 1, 2 and 3 NV). The apo mimetics can be used alone or in conjunction with other therapeutic agents, such as a complement inhibitor and/or an anti-angiogenic agent, to treat AMD, including atrophic AMD and neovascular AMD, and other eye disorders.

  本公开提供了可用于治疗老年性黄斑变性（AMD）和其他眼部疾病的载脂蛋白（apo）模拟物。载脂蛋白模拟物可以是模拟载脂蛋白（如载脂蛋白A-I和载脂蛋白E）清脂作用的肽/多肽。载脂蛋白模拟物还能发挥其他有益作用，如减少炎症、氧化应激和新生血管。载脂蛋白模拟物可用于治疗AMD的任何阶段（包括早期、中期和晚期），以及AMD的任何表型，包括地理萎缩（GA）（包括非中心性GA和中心性GA）和新生血管（NV）（包括1型、2型和3型NV）。载脂蛋白模拟物可单独使用，也可与其他治疗剂（如补体抑制剂和/或抗血管生成剂）联合使用，用于治疗AMD（包括萎缩性AMD和新生血管性AMD）和其他眼部疾病。
• Topical delivery of therapeutic agents using cell-penetrating peptides for the treatment of age-related macular degeneration and other eye diseases
  申请人：MacRegen, Inc.

  公开号：US10905770B2

  公开（公告）日：2021-02-02

  The present disclosure provides therapeutic agents for the treatment of age-related macular degeneration (AMD) and other eye disorders. One or more therapeutic agents can be used to treat any stages (including the early, intermediate and advance stages) of AMD, and any phenotypes of AMD, including geographic atrophy (including non-central GA and central GA) and neovascularization (including types 1, 2 and 3 NV). In some embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent, an antioxidant, an anti-inflammatory agent, a complement inhibitor, a neuroprotector or an anti-angiogenic agent, or any combination thereof. In certain embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent (e.g., an apolipoprotein mimetic or/and a statin). In some embodiments, the one or more therapeutic agents are mixed with, non-covalently associated with or covalently bonded to a cell-penetrating peptide (CPP), encapsulated in CPP-conjugated nanoparticles, micelles or liposomes, or modified (e.g., stapled, prenylated, lipidated or coupled to a small-molecule α-helix mimic) to acquire membrane-translocating ability. In certain embodiments, the one or more therapeutic agents are administered by eye drop.

  本公开提供了用于治疗老年性黄斑变性（AMD）和其他眼部疾病的治疗剂。一种或多种治疗剂可用于治疗AMD的任何阶段（包括早期、中期和晚期），以及AMD的任何表型，包括地理萎缩（包括非中心性GA和中心性GA）和新生血管（包括1型、2型和3型NV）。在某些实施方案中，一种或多种治疗剂是或包括抗血脂异常剂、抗氧化剂、抗炎剂、补体抑制剂、神经保护剂或抗血管生成剂，或它们的任意组合。在某些实施方案中，一种或多种治疗剂是或包括抗血脂异常剂（例如，载脂蛋白模拟物或/和他汀类药物）。在某些实施方案中，一种或多种治疗剂与细胞穿透肽（CPP）混合、非共价结合或共价键合，包封在CPP共轭的纳米颗粒、胶束或脂质体中，或进行修饰（例如，钉合、前酰化、脂质化或与小分子α-螺旋模拟物偶联）以获得膜转运能力。在某些实施方案中，一种或多种治疗剂通过滴眼液给药。
• VERWENDUNG VON PYRIDIN-2,4-DICARBONS UREDIAMIDEN UND PYRIMID IN-4,6-DICARBONS UREDIAMIDEN ZUR SELEKTIVEN INHIBIERUNG VON KOLLAGENASEN
  申请人：Sanofi-Aventis Deutschland GmbH

  公开号：EP1455790B1

  公开（公告）日：2008-03-26