(2R)-N'-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(3-morpholin-4-ylpropylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide

• 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: (2R)-N'-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(3-morpholin-4-ylpropylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
• 化学式: C₂₆H₃₉N₅O₅
• 分子量: 501.626
• InChiKey: YIEJUKBUYFONED-XXBNENTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  136
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-L-色氨酸 在 盐酸 、 氢氧化钾 、 盐酸羟胺 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 32.0h， 生成 (2R)-N'-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(3-morpholin-4-ylpropylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study

  摘要：

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

  DOI：

  10.1021/jm970494j

文献信息

• EP0690841A4
  申请人：——

  公开号：EP0690841A4

  公开（公告）日：1996-03-13
• SYNTHETIC MATRIX METALLOPROTEASE INHIBITORS AND USES THEREOF
  申请人：GLYCOMED INCORPORATED

  公开号：EP0690841A1

  公开（公告）日：1996-01-10
• [EN] SYNTHETIC MATRIX METALLOPROTEASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS SYNTHETIQUES DE METALLOPROTEASES MATRICIELLES ET UTILISATIONS CORRESPONDANTES
  申请人：GLYCOMED INCORPORATED

  公开号：WO1995019965A1

  公开（公告）日：1995-07-27

  (EN) Synthetic mammalian matrix metalloprotease inhibitors are disclosed that are useful for treating or preventing diseases wherein said diseases are caused by unwanted mammalian matrix metalloprotease activity and include skin disorders, keratoconus, restenosis, rheumatoid arthritis, wounds, cancer, angiogenesis and shock.(FR) La présente invention concerne des inhibiteurs synthétiques de métalloprotéases matricielles des mammifères. Ces inhibiteurs conviennent particulièrement au traitement et à la prévention d'affections dans le cas où lesdites affections sont provoquées par l'activité non souhaitée de métalloprotéases matricielles des mammifères, ces affections incluant les affections cutanées, le kératocône, la resténose, la polyarthrite rhumatoïde, les lésions, le cancer, l'angiogenèse et l'état de choc.
• Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study
  作者：Daniel E. Levy、France Lapierre、Weisheng Liang、Wenqing Ye、Christopher W. Lange、Xiaoyuan Li、Damian Grobelny、Marie Casabonne、David Tyrrell、Kevin Holme、Alex Nadzan、Richard E. Galardy

  DOI：10.1021/jm970494j

  日期：1998.1.1

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.