(R)-N⁴-Hydroxy-N¹-((S)-1-methylcarbamoyl-2-phenyl-ethyl)-2-(4-phenoxy-butyl)-succinamide

• 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)-N⁴-Hydroxy-N¹-((S)-1-methylcarbamoyl-2-phenyl-ethyl)-2-(4-phenoxy-butyl)-succinamide
• 英文别名: (R)-N4-hydroxy-N1-((S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl)-2-(4-phenoxybutyl)succinamide；(2R)-N'-hydroxy-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]-2-(4-phenoxybutyl)butanediamide
• 化学式: C₂₄H₃₁N₃O₅
• 分子量: 441.527
• InChiKey: ABOVSYRJLZIGMD-CTNGQTDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,6-己二醇 在 palladium dihydroxide N-甲基吗啉 、 lithium hydroxide 、 重铬酸吡啶 、 正丁基锂 、 草酰氯 、 氰基磷酸二乙酯 、 1,4-环己二烯 、 O-(三甲基硅)羟胺 、 水 、 双氧水 、 sodium hydride 、 三乙胺 、 二异丙胺 、 N,N-二甲基甲酰胺 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.25h， 生成 (R)-N⁴-Hydroxy-N¹-((S)-1-methylcarbamoyl-2-phenyl-ethyl)-2-(4-phenoxy-butyl)-succinamide
  参考文献：
  名称：

  Inhibition of Matrix Metalloproteinases by Hydroxamates Containing Heteroatom-Based Modifications of the P1' Group

  摘要：

  In this study, structure-based drug design of matrix metalloproteinase inhibitors [human fibroblast collagenase (HFC), human fibroblast stromelysin (HFS), and human neutrophil collagenase (HNC)] was utilized in the development of potent hydroxamates which contain novel, heteroatom-based modifications of the P-1' group. A series containing a P-1' butyramide group resulted in a nanomolar potent and selective HNC inhibitor as well as a dual HFS/HNC inhibitor. Benzylic others with a four- or five-carbon methylene linker in the P-1' position also produced nanomolar potent HFS/HNC inhibition and micromolar potent HFC inhibition as expected. Surprisingly, the phenolic ethers of the same overall length as the benzylic ethers showed nanomolar potencies against HFC, as well as HFS and HNC. The potency profile of the phenolic ethers was optimized by structure-activity relationships of the phenolic group and the C-terminal amide. These inhibitors may help elucidate the in vivo roles of matrix metalloproteinases in normal and disease states.

  DOI：

  10.1021/jm00014a010

文献信息

• Metalloprotein inhibitors containing nitrogen based ligands
  申请人：Cohen Seth M.

  公开号：US20120135959A1

  公开（公告）日：2012-05-31

  Provided herein metalloproteinase inhibitors containing nitrogen or mixed nitrogen/oxygen donating zinc binding groups. Also provided are pharmaceutical compositions containing the compounds and methods of treating preventing or ameliorating the diseases associated with metalloproteinase activity using the compounds and compositions.

  本文提供了含有氮或混合氮/氧供体锌结合基团的金属蛋白酶抑制剂。还提供了含有这些化合物的药物组合物，以及使用这些化合物和组合物治疗、预防或改善与金属蛋白酶活性相关的疾病的方法。
• Statin-MMP inhibitor combinations
  申请人：——

  公开号：US20020049237A1

  公开（公告）日：2002-04-25

  The invention is a pharmaceutical composition comprising an MMP inhibitor and a statin, said composition being useful for treating vascular diseases.

  这项发明是一种药物组合物，包括MMP抑制剂和他汀类药物，该组合物可用于治疗血管疾病。
• Use of matrix metalloproteinase inhibitors for treating neurological disorders and promoting wound healing
  申请人：WARNER-LAMBERT COMPANY LLC

  公开号：EP1366765A1

  公开（公告）日：2003-12-03

  Matrix metalloproteinase inhibitors are useful for preventing and treating neurological disorders and in promoting wound healing.

  基质金属蛋白酶抑制剂可用于预防和治疗神经系统疾病以及促进伤口愈合。
• HYDROXAMIC ACID AND CARBOXYLIC ACID DERIVATIVES, PROCESS FOR THEIR PREPARATION AND USE THEREOF
  申请人：SANOFI WINTHROP, INC.

  公开号：EP0749302A1

  公开（公告）日：1996-12-27
• EP0749302A4
  申请人：——

  公开号：EP0749302A4

  公开（公告）日：1999-08-25