di-tert-butyl (2S,4R)-4-benzylpyrrolidine-1,2-dicarboxylate | 1356352-02-7

• 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: di-tert-butyl (2S,4R)-4-benzylpyrrolidine-1,2-dicarboxylate
• CAS: 1356352-02-7
• 化学式: C₂₁H₃₁NO₄
• 分子量: 361.481
• InChiKey: PSAZBUJQXDEJBQ-SJORKVTESA-N

物化性质

• 沸点：
  438.7±38.0 °C(Predicted)
• 密度：
  1.087±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  55.84
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  di-tert-butyl (2S,4R)-4-benzylpyrrolidine-1,2-dicarboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 反-4-苄基-L-脯氨酸
  参考文献：
  名称：

  Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists

  摘要：

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.

  DOI：

  10.1021/jm201533b
• 作为产物：
  描述：

  (S)-N-叔丁氧羰基-2-吡咯烷酮-5-甲酸叔丁酯 在 三乙基硼氢化锂 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 di-tert-butyl (2S,4R)-4-benzylpyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  Discovery of a Novel Class of Potent and Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists

  摘要：

  A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.

  DOI：

  10.1021/jm201533b

文献信息

• Synthesis of 4-(Arylmethyl)proline Derivatives
  作者：Simon Loosli、Carlotta Foletti、Marcus Papmeyer、Helma Wennemers

  DOI：10.1055/s-0037-1611672

  日期：2019.3

  A synthesis of 4-(arylmethyl)proline by using Suzuki cross-couplings was developed. The route permits access to a variety of 4-substituted proline derivatives bearing various aryl moieties that expand the toolbox of proline analogues for studies in chemistry and ­biology.

  开发了使用 Suzuki 交叉偶联合成 4-（芳甲基）脯氨酸。该路线允许获得各种带有各种芳基部分的 4-取代脯氨酸衍生物，这些衍生物扩展了脯氨酸类似物用于化学和生物学研究的工具箱。