methyl 3-{[4-[[(tert-butyldimethylsilyl)oxy]methyl]benzyl]sulfonyl}propanoate | 1001026-35-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 3-{[4-[[(tert-butyldimethylsilyl)oxy]methyl]benzyl]sulfonyl}propanoate
• 英文别名: Methyl 3-[[4-[[tert-butyl(dimethyl)silyl]oxymethyl]phenyl]methylsulfonyl]propanoate
• CAS: 1001026-35-2
• 化学式: C₁₈H₃₀O₅SSi
• 分子量: 386.585
• InChiKey: YLSOECMDGVXNEO-UHFFFAOYSA-N

物化性质

• 沸点：
  490.4±40.0 °C(Predicted)
• 密度：
  1.092±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-{[4-[[(tert-butyldimethylsilyl)oxy]methyl]benzyl]sulfonyl}propanoate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium methylate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 17.25h， 生成 ethyl 5-cyano-6-(3-{[[4-(hydroxymethyl)benzyl]sulfonyl]carbamoyl}azetidin-1-yl)-2-methylnicotinate
  参考文献：
  名称：

  Lead Optimization of Ethyl 6-Aminonicotinate Acyl Sulfonamides as Antagonists of the P2Y₁₂ Receptor. Separation of the Antithrombotic Effect and Bleeding for Candidate Drug AZD1283

  摘要：

  Synthesis and structure-activity relationships of ethyl 6-aminonicotinate acyl sulfonamides, which are potent antagonists of the P2Y(12) receptor, are presented. Shifting from 5-chlorothienyl to benzyl sulfonamides significantly increased the potency in the residual platelet count assay. Evaluation of PK parameters in vivo in dog for six compounds showed a 10-fold higher clearance for the azetidines than for the matched-pair piperidines. In a modified Folts model in dog, both piperidine 3 and azetidine 13 dose-dependently induced increases in blood flow and inhibition of ADP-induced platelet aggregation with antithrombotic ED50 values of 3.0 and 10 mu g/kg/min, respectively. The doses that induced a larger than 3-fold increase in bleeding time were 33 and 100 mu g/kg/min for 3 and 13, respectively. Thus, the therapeutic index (TI) was >= 10 for both compounds. On the basis of these data, compound 3 was progressed into human clinical trials as candidate drug AZD1283.

  DOI：

  10.1021/jm400820m
• 作为产物：
  描述：

  4-(氯甲基)苯甲基醇 在 咪唑 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 17.0h， 生成 methyl 3-{[4-[[(tert-butyldimethylsilyl)oxy]methyl]benzyl]sulfonyl}propanoate
  参考文献：
  名称：

  Lead Optimization of Ethyl 6-Aminonicotinate Acyl Sulfonamides as Antagonists of the P2Y₁₂ Receptor. Separation of the Antithrombotic Effect and Bleeding for Candidate Drug AZD1283

  摘要：

  Synthesis and structure-activity relationships of ethyl 6-aminonicotinate acyl sulfonamides, which are potent antagonists of the P2Y(12) receptor, are presented. Shifting from 5-chlorothienyl to benzyl sulfonamides significantly increased the potency in the residual platelet count assay. Evaluation of PK parameters in vivo in dog for six compounds showed a 10-fold higher clearance for the azetidines than for the matched-pair piperidines. In a modified Folts model in dog, both piperidine 3 and azetidine 13 dose-dependently induced increases in blood flow and inhibition of ADP-induced platelet aggregation with antithrombotic ED50 values of 3.0 and 10 mu g/kg/min, respectively. The doses that induced a larger than 3-fold increase in bleeding time were 33 and 100 mu g/kg/min for 3 and 13, respectively. Thus, the therapeutic index (TI) was >= 10 for both compounds. On the basis of these data, compound 3 was progressed into human clinical trials as candidate drug AZD1283.

  DOI：

  10.1021/jm400820m

文献信息

• WO2008/4946
  申请人：——

  公开号：——

  公开（公告）日：——