methyl 4-((tert-butyldimethylsilyloxy)methyl)-2-neopentylpyridine-1(2H)-carboxylate | 1251843-10-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 4-((tert-butyldimethylsilyloxy)methyl)-2-neopentylpyridine-1(2H)-carboxylate
• 英文别名: methyl 4-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-(2,2-dimethylpropyl)-2H-pyridine-1-carboxylate
• CAS: 1251843-10-3
• 化学式: C₁₉H₃₅NO₃Si
• 分子量: 353.577
• InChiKey: UUSXBEIKTUKDPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.34
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-((tert-butyldimethylsilyloxy)methyl)-2-neopentylpyridine-1(2H)-carboxylate 在 ruthenium trichloride 、 sodium periodate 、 Adam’s catalyst 、 盐酸羟胺 、 四丁基氟化铵 、 水 、 氢气 、 sodium hydroxide 、 di(2H-imidazol-2-yl)methanone 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 水 、 乙酸乙酯 、 乙腈 为溶剂， -30.0~20.0 ℃ 、600.01 kPa 条件下， 反应 39.17h， 生成 cis-methyl 2-neopentyl-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein–Protein Interaction

  摘要：

  A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC50 of 0.44 mu M, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.

  DOI：

  10.1021/ml400526d
• 作为产物：
  描述：

  4-吡啶甲醇 在 咪唑 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.33h， 生成 methyl 4-((tert-butyldimethylsilyloxy)methyl)-2-neopentylpyridine-1(2H)-carboxylate
  参考文献：
  名称：

  Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein–Protein Interaction

  摘要：

  A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC50 of 0.44 mu M, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.

  DOI：

  10.1021/ml400526d