(S)-2-{[3'-(4-chloro-2,5-dimethylphenylsulfonylamino)-3,5-dimethyl-biphenyl-4-carbonyl]-amino}-4-tertbutoxycarbonylamino-butyric acid methyl ester | 1403762-27-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-2-{[3'-(4-chloro-2,5-dimethylphenylsulfonylamino)-3,5-dimethyl-biphenyl-4-carbonyl]-amino}-4-tertbutoxycarbonylamino-butyric acid methyl ester
• 英文别名: methyl (2S)-2-[[4-[3-[(4-chloro-2,5-dimethylphenyl)sulfonylamino]phenyl]-2,6-dimethylbenzoyl]amino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 1403762-27-5
• 化学式: C₃₃H₄₀ClN₃O₇S
• 分子量: 658.216
• InChiKey: FDPBTVPCRYCCNP-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  45
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-2-{[3'-(4-chloro-2,5-dimethylphenylsulfonylamino)-3,5-dimethyl-biphenyl-4-carbonyl]-amino}-4-tertbutoxycarbonylamino-butyric acid methyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 2.0h， 以52%的产率得到4-[3-[(4-chloro-2,5-dimethylphenyl)sulfonylamino]phenyl]-2,6-dimethyl-N-[(3S)-2-oxopyrrolidin-3-yl]benzamide
  参考文献：
  名称：

  An Oral Sphingosine 1-Phosphate Receptor 1 (S1P₁) Antagonist Prodrug with Efficacy in Vivo: Discovery, Synthesis, and Evaluation

  摘要：

  A prodrug approach to optimize the oral exposure :of a series of sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists for chronic efficacy studies led to the discovery of dimethylphenylsulfonylamino)-3,5-dimethylbiphenyl-4-carbonyl]-methylamino}-4-dimethylaminobutyric acid methyl ester 14. Methyl ester prodrug 14 is hydrolyzed in vivo to the corresponding carboxylic, acid 15, a potent and selective S1P(1) antagonist.: Oral; administration of the prodrug 14 induces sustained peripheral blood lymphocyte reduction.. in rats. In a rat: cardiac transplantation model coadministration of a nonefficacious dose of prodrung 14 with a nonefficacious dose of sotrastaurin (19), a protein kinase C inhibitor, or everolimus mTOR inhibitor, effectively prolonged the survival time of rat cardiac allografts. This demonstrates that clinically useful immunomodulation mediated by the S1P(1) receptor can be achieved with an S1P(1) antagonist generated in vivo after oral administration of its prodrug.

  DOI：

  10.1021/jm3009508
• 作为产物：
  描述：

  3-氨基苯硼酸 在 吡啶 、 四(三苯基膦)钯 、 氯化亚砜 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 (S)-2-{[3'-(4-chloro-2,5-dimethylphenylsulfonylamino)-3,5-dimethyl-biphenyl-4-carbonyl]-amino}-4-tertbutoxycarbonylamino-butyric acid methyl ester
  参考文献：
  名称：

  An Oral Sphingosine 1-Phosphate Receptor 1 (S1P₁) Antagonist Prodrug with Efficacy in Vivo: Discovery, Synthesis, and Evaluation

  摘要：

  A prodrug approach to optimize the oral exposure :of a series of sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists for chronic efficacy studies led to the discovery of dimethylphenylsulfonylamino)-3,5-dimethylbiphenyl-4-carbonyl]-methylamino}-4-dimethylaminobutyric acid methyl ester 14. Methyl ester prodrug 14 is hydrolyzed in vivo to the corresponding carboxylic, acid 15, a potent and selective S1P(1) antagonist.: Oral; administration of the prodrug 14 induces sustained peripheral blood lymphocyte reduction.. in rats. In a rat: cardiac transplantation model coadministration of a nonefficacious dose of prodrung 14 with a nonefficacious dose of sotrastaurin (19), a protein kinase C inhibitor, or everolimus mTOR inhibitor, effectively prolonged the survival time of rat cardiac allografts. This demonstrates that clinically useful immunomodulation mediated by the S1P(1) receptor can be achieved with an S1P(1) antagonist generated in vivo after oral administration of its prodrug.

  DOI：

  10.1021/jm3009508