Boc-(ε-hydroxy)-Nle-(2-thiazolyl) | 474081-22-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Boc-(ε-hydroxy)-Nle-(2-thiazolyl)
• 英文别名: tert-butyl N-[(2S)-6-hydroxy-1-oxo-1-(1,3-thiazol-2-yl)hexan-2-yl]carbamate
• CAS: 474081-22-6
• 化学式: C₁₄H₂₂N₂O₄S
• 分子量: 314.406
• InChiKey: QMGAMWFUGFZDDR-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 Boc-(ε-hydroxy)-Nle-(2-thiazolyl) 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Unique Overlap in the Prerequisites for Thrombin Inhibition and Oral Bioavailability Resulting in Potent Oral Antithrombotics

  摘要：

  Despite intense research over the last 10 years, aided by the availability of X-ray structures of enzyme-inhibitor complexes, only very few truly orally active thrombin inhibitors have been found. We conducted a comprehensive study starting with peptide transition state analogues (TSA). Both hydrophobic nonpeptide analogues as well as hydrophilic peptidic analogues were synthesized. The bioavailability in rats and dogs could be drastically altered depending on the overall charge distribution in the molecule. Compound 27, a tripeptide TSA inhibitor of thrombin, showed an oral bioavailability of 32% in rats and 71% in dogs, elimination half-lives being 58 and 108 min, respectively. The thrombin inhibition constant of compound 27 was 1.1 nM, and in an in vivo arterial flow model, the ED50 was 5.4 nmol/kg(.)min, comparable to known non-TSA inhibitors. A molecular design was found that combines antithrombotic efficiency with oral bioavailability at low dosages.

  DOI：

  10.1021/jm011110z
• 作为产物：
  描述：

  BOC-L-6-羟基正亮氨酸 在 正丁基锂 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 Boc-(ε-hydroxy)-Nle-(2-thiazolyl)
  参考文献：
  名称：

  Unique Overlap in the Prerequisites for Thrombin Inhibition and Oral Bioavailability Resulting in Potent Oral Antithrombotics

  摘要：

  Despite intense research over the last 10 years, aided by the availability of X-ray structures of enzyme-inhibitor complexes, only very few truly orally active thrombin inhibitors have been found. We conducted a comprehensive study starting with peptide transition state analogues (TSA). Both hydrophobic nonpeptide analogues as well as hydrophilic peptidic analogues were synthesized. The bioavailability in rats and dogs could be drastically altered depending on the overall charge distribution in the molecule. Compound 27, a tripeptide TSA inhibitor of thrombin, showed an oral bioavailability of 32% in rats and 71% in dogs, elimination half-lives being 58 and 108 min, respectively. The thrombin inhibition constant of compound 27 was 1.1 nM, and in an in vivo arterial flow model, the ED50 was 5.4 nmol/kg(.)min, comparable to known non-TSA inhibitors. A molecular design was found that combines antithrombotic efficiency with oral bioavailability at low dosages.

  DOI：

  10.1021/jm011110z