3,5-dichloro-6-methyl-1-(2-tert-butoxycarbonylamino-6-methyl-5-methylenecarboxamidomethylpyridinyl)pyrazinone | 199296-23-6

• 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: 3,5-dichloro-6-methyl-1-(2-tert-butoxycarbonylamino-6-methyl-5-methylenecarboxamidomethylpyridinyl)pyrazinone
• 英文别名: tert-butyl N-[5-[[[2-(3,5-dichloro-2-methyl-6-oxopyrazin-1-yl)acetyl]amino]methyl]-6-methylpyridin-2-yl]carbamate
• CAS: 199296-23-6
• 化学式: C₁₉H₂₃Cl₂N₅O₄
• 分子量: 456.329
• InChiKey: WJRREFHYMZHQGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-dichloro-6-methyl-1-(2-tert-butoxycarbonylamino-6-methyl-5-methylenecarboxamidomethylpyridinyl)pyrazinone 在 盐酸 作用下， 以 1,4-二氧六环 、 乙酸乙酯 为溶剂， 反应 17.17h， 生成 N-(6-Amino-2-methyl-pyridin-3-ylmethyl)-2-(5-chloro-6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide
  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：

  2-氨基-5-溴-6-甲基吡啶 在 palladium on activated charcoal N-甲基吗啉 、 4-二甲氨基吡啶 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.0h， 生成 3,5-dichloro-6-methyl-1-(2-tert-butoxycarbonylamino-6-methyl-5-methylenecarboxamidomethylpyridinyl)pyrazinone
  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

文献信息

• Efficacious, Orally Bioavailable Thrombin Inhibitors Based on 3-Aminopyridinone or 3-Aminopyrazinone Acetamide Peptidomimetic Templates
  作者：Philip E. J. Sanderson、Terry A. Lyle、Kellie J. Cutrona、Dona L. Dyer、Bruce D. Dorsey、Colleen M. McDonough、Adel M. Naylor-Olsen、I-Wu Chen、Zhongguo Chen、Jacquelynn J. Cook、Carolyn M. Cooper、Stephen J. Gardell、Timothy R. Hare、Julie A. Krueger、S. Dale Lewis、Jiunn H. Lin、Bobby J. Lucas,、Elizabeth A. Lyle、Joseph J. Lynch,、Maria T. Stranieri、Kari Vastag、Youwei Yan、Jules A. Shafer、Joseph P. Vacca

  DOI：10.1021/jm980368v

  日期：1998.11.1

  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.