[5-Chloro-6-methyl-3-((R)-1-methyl-2-phenyl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid benzyl ester | 1027261-93-3

• 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: [5-Chloro-6-methyl-3-((R)-1-methyl-2-phenyl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid benzyl ester
• 英文别名: benzyl 2-[3-chloro-2-methyl-6-oxo-5-[[(2R)-1-phenylpropan-2-yl]amino]pyrazin-1-yl]acetate
• CAS: 1027261-93-3
• 化学式: C₂₃H₂₄ClN₃O₃
• 分子量: 425.915
• InChiKey: HWCQXOKTTVCYSV-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [5-Chloro-6-methyl-3-((R)-1-methyl-2-phenyl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid benzyl ester 在 palladium on activated charcoal 氢氧化钾 、 lithium hydroxide 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 15.0h， 生成 [6-Methyl-3-((R)-1-methyl-2-phenyl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid
  参考文献：
  名称：

  Efficacious, Orally Bioavailable Thrombin Inhibitors Based on 3-Aminopyridinone or 3-Aminopyrazinone Acetamide Peptidomimetic Templates

  摘要：

  We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3-sulfonylaminopyridinone core. Compound 3 (L-375,378), the closest aminopyrazinone analogue of 1, has comparable selectivity and slightly decreased efficacy but significantly improved pharmacokinetics in rats, dogs, and monkeys to 1. We have developed an efficient and versatile synthesis of 3, and this compound has been chosen for further preclinical and clinical development.

  DOI：

  10.1021/jm980368v
• 作为产物：
  描述：

  甘氨酸苄酯盐酸盐 以 二氯甲烷 、 乙酸乙酯 、 邻二氯苯 为溶剂， 反应 21.0h， 生成 [5-Chloro-6-methyl-3-((R)-1-methyl-2-phenyl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-acetic acid benzyl ester
  参考文献：
  名称：

  Efficacious, Orally Bioavailable Thrombin Inhibitors Based on 3-Aminopyridinone or 3-Aminopyrazinone Acetamide Peptidomimetic Templates

  摘要：

  We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3-sulfonylaminopyridinone core. Compound 3 (L-375,378), the closest aminopyrazinone analogue of 1, has comparable selectivity and slightly decreased efficacy but significantly improved pharmacokinetics in rats, dogs, and monkeys to 1. We have developed an efficient and versatile synthesis of 3, and this compound has been chosen for further preclinical and clinical development.

  DOI：

  10.1021/jm980368v