(2S)-2-[[(2R)-2-(benzylsulfonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]propanoic acid | 256666-30-5

• 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-[[(2R)-2-(benzylsulfonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]propanoic acid
• CAS: 256666-30-5
• 化学式: C₁₇H₂₆N₂O₆S
• 分子量: 386.469
• InChiKey: SMWKWKKEHBURFH-GXTWGEPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-2-[[(2R)-2-(benzylsulfonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]propanoic acid 在 PS-carbodiimide 、 1-羟基苯并三唑 作用下， 以 二氯甲烷 为溶剂， 反应 3.17h， 生成 diphenyl 1-[(N-α-toluenesulfonyl-D-seryl)-L-alanyl]amino-2-(4-guanidinophenyl)ethanephosphonate trifluoroacetate
  参考文献：
  名称：

  Diphenyl Phosphonate Inhibitors for the Urokinase-Type Plasminogen Activator:  Optimization of the P4 Position

  摘要：

  This paper describes the structure-activity relationship in a series of tripeptidyl diphenyl phosphonate irreversible urokinase plasminogen activator (uPA) inhibitors, originally derived from an arginyltripeptide. uPA is considered an interesting target in anticancer drug design. The selectivity of these inhibitors for uPA is enhanced by the optimization of the P4 position. The most interesting compound shows an IC50 of 5 nM, with a selectivity index of more than 3000 toward other Arg/Lys-specific proteases such as tissue-type plasminogen activator, plasmin, factor Xa, and thrombin. A synthetic strategy for the preparation of small libraries of diphenyl phosphonate analogues of capped tripeptides is described. It is shown that uPA is irreversibly inhibited, and interactions with the active site were modeled. Finally, a diparacetamol phosphonate analogue was developed to circumvent the release of cytotoxic phenol.

  DOI：

  10.1021/jm060622g
• 作为产物：
  描述：

  Fmoc-L-丙氨酸 、 Fmoc-O-叔丁基-D-丝氨酸 、 苄磺酰氯 以49%的产率得到(2S)-2-[[(2R)-2-(benzylsulfonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]propanoic acid
  参考文献：
  名称：

  Diphenyl Phosphonate Inhibitors for the Urokinase-Type Plasminogen Activator:  Optimization of the P4 Position

  摘要：

  This paper describes the structure-activity relationship in a series of tripeptidyl diphenyl phosphonate irreversible urokinase plasminogen activator (uPA) inhibitors, originally derived from an arginyltripeptide. uPA is considered an interesting target in anticancer drug design. The selectivity of these inhibitors for uPA is enhanced by the optimization of the P4 position. The most interesting compound shows an IC50 of 5 nM, with a selectivity index of more than 3000 toward other Arg/Lys-specific proteases such as tissue-type plasminogen activator, plasmin, factor Xa, and thrombin. A synthetic strategy for the preparation of small libraries of diphenyl phosphonate analogues of capped tripeptides is described. It is shown that uPA is irreversibly inhibited, and interactions with the active site were modeled. Finally, a diparacetamol phosphonate analogue was developed to circumvent the release of cytotoxic phenol.

  DOI：

  10.1021/jm060622g

文献信息

• Non-covalent inhibitors of urokinase and blood vessel formation
  申请人：Wilex AG

  公开号：EP1808440A1

  公开（公告）日：2007-07-18

  Novel compounds having activity as non-covalent inhibitors of urokinase and having activity in reducing or inhibiting blood vessel formation are provided. These compounds have P1 a group having an amidino or guanidino moiety or derivative thereof. These compounds are useful in vitro for monitoring plasminogen activator levels and in vivo in treatment of conditions which are ameliorated by inhibition of or decreased activity of urokinase and in treating pathologic conditions wherein blood vessel formation is related to a pathologic condition.

  本研究提供了具有作为尿激酶非共价抑制剂的活性和减少或抑制血管形成的活性的新型化合物。 这些化合物的 P1 基团具有脒基或胍基或其衍生物。 这些化合物在体外可用于监测纤溶酶原激活剂的水平，在体内可用于治疗因抑制或降低尿激酶活性而改善的病症，以及治疗血管形成与病症有关的病症。
• Diphenyl Phosphonate Inhibitors for the Urokinase-Type Plasminogen Activator:  Optimization of the P4 Position
  作者：Jurgen Joossens、Pieter Van der Veken、Georgiana Surpateanu、Anne-Marie Lambeir、Ibrahim El-Sayed、Omar M. Ali、Koen Augustyns、Achiel Haemers

  DOI：10.1021/jm060622g

  日期：2006.9.1

  This paper describes the structure-activity relationship in a series of tripeptidyl diphenyl phosphonate irreversible urokinase plasminogen activator (uPA) inhibitors, originally derived from an arginyltripeptide. uPA is considered an interesting target in anticancer drug design. The selectivity of these inhibitors for uPA is enhanced by the optimization of the P4 position. The most interesting compound shows an IC50 of 5 nM, with a selectivity index of more than 3000 toward other Arg/Lys-specific proteases such as tissue-type plasminogen activator, plasmin, factor Xa, and thrombin. A synthetic strategy for the preparation of small libraries of diphenyl phosphonate analogues of capped tripeptides is described. It is shown that uPA is irreversibly inhibited, and interactions with the active site were modeled. Finally, a diparacetamol phosphonate analogue was developed to circumvent the release of cytotoxic phenol.