N-(6-amino-2-methyl-pyridin-3-ylmethyl)-2-(6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide | 199294-70-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-(6-amino-2-methyl-pyridin-3-ylmethyl)-2-(6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide
• 英文别名: N-[(6-amino-2-methyl-3-pyridinyl)methyl]-2-[6-methyl-2-oxo-3-(2-phenylethylamino)-1-pyrazinyl]acetamide；N-[(6-amino-2-methylpyridin-3-yl)methyl]-2-[6-methyl-2-oxo-3-(2-phenylethylamino)pyrazin-1-yl]acetamide
• CAS: 199294-70-7
• 化学式: C₂₂H₂₆N₆O₂
• 分子量: 406.487
• InChiKey: PVDHYBJORRALSQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(6-amino-2-methyl-pyridin-3-ylmethyl)-2-(6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide 、 溴乙醛 在 potassium acetate 作用下， 以 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(5-Methyl-imidazo[1,2-a]pyridin-6-ylmethyl)-2-(6-methyl-2-oxo-3-phenethylamino-2H-pyrazin-1-yl)-acetamide
  参考文献：
  名称：

  Azaindoles: moderately basic P1 groups for enhancing the selectivity of thrombin inhibitors

  摘要：

  Starting from a 2-amino-6-methylpyridine PI group and following a strategy of enlarging it whilst reducing its polarity, we have developed a series of potent, moderately basic azaindoles which are intrinsically much more selective for thrombin versus trypsin. Certain pyrazinone acetamide azaindole derivatives have pharmacokinetic parameters after oral administration to dogs, or efficacy in vitro, comparable to an optimized pyrazinone acetamide 2-amino-6-methylpyridine derivative. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00017-9
• 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 、 盐酸 、 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 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、413.68 kPa 条件下， 反应 33.0h， 生成 N-(6-amino-2-methyl-pyridin-3-ylmethyl)-2-(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

文献信息

• Methods of Inhibiting MASP-2 for the Treatment and/or Prevention of Coronavirus-induced Acute Respiratory Distress Syndrome
  申请人：Omeros Corporation

  公开号：US20210292436A1

  公开（公告）日：2021-09-23

  In one aspect, the invention provides methods for treating, inhibiting, alleviating, or preventing acute respiratory distress syndrome, pneumonia, or some other pulmonary or other manifestation of coronavirus infection, such as thrombosis, in a mammalian subject infected with coronavirus, such as SARS-CoV-2. The methods comprise the step of administering to a subject infected with coronavirus an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In one embodiment, the MASP-2 inhibitory agent is a MASP-2 monoclonal antibody, or fragment thereof that specifically binds to a portion of SEQ ID NO:6. In one embodiment, the MASP-2 inhibitory agent is a small molecule MASP-2 inhibitory compound. In one embodiment, the subject is a human subject suffering from COVID-19-induced acute respiratory distress syndrome (ARDS) and requires supplemental oxygen prior to treatment and the MASP-2 inhibitory agent is administered in an amount sufficient to discontinue the need for supplemental oxygen.
• [EN] METHODS OF INHIBITING MASP-2 FOR THE TREATMENT AND/OR PREVENTION OF CORONAVIRUS-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME<br/>[FR] PROCÉDÉS D'INHIBITION DE MASP -2 POUR LE TRAITEMENT ET/OU LA PRÉVENTION DU SYNDROME DE DÉTRESSE RESPIRATOIRE AIGUË INDUITE PAR LE CORONAVIRUS
  申请人：OMEROS CORP

  公开号：WO2021178902A1

  公开（公告）日：2021-09-10

  In one aspect, the invention provides methods for treating, inhibiting, alleviating, or preventing acute respiratory distress syndrome, pneumonia, or some other pulmonary or other manifestation of coronavirus infection, such as thrombosis, in a mammalian subject infected with coronavirus, such as SARS-CoV-2. The methods comprise the step of administering to a subject infected with coronavirus an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In one embodiment, the MASP-2 inhibitory agent is a MASP-2 monoclonal antibody, or fragment thereof that specifically binds to a portion of SEQ ID NO:6. In one embodiment, the MASP-2 inhibitory agent is a small molecule MASP-2 inhibitory compound. In one embodiment, the subject is a human subject suffering from COVID- 19-induced acute respiratory distress syndrome (ARDS) and requires supplemental oxygen prior to treatment and the MASP-2 inhibitory agent is administered in an amount sufficient to discontinue the need for supplemental oxygen.
• Azaindoles: moderately basic P1 groups for enhancing the selectivity of thrombin inhibitors
  作者：Philip E.J. Sanderson、Matthew G. Stanton、Bruce D. Dorsey、Terry A. Lyle、Colleen McDonough、William M. Sanders、Kelly L. Savage、Adel M. Naylor-Olsen、Julie A. Krueger、S.Dale Lewis、Bobby J. Lucas、Joseph J. Lynch、Youwei Yan

  DOI：10.1016/s0960-894x(03)00017-9

  日期：2003.3

  Starting from a 2-amino-6-methylpyridine PI group and following a strategy of enlarging it whilst reducing its polarity, we have developed a series of potent, moderately basic azaindoles which are intrinsically much more selective for thrombin versus trypsin. Certain pyrazinone acetamide azaindole derivatives have pharmacokinetic parameters after oral administration to dogs, or efficacy in vitro, comparable to an optimized pyrazinone acetamide 2-amino-6-methylpyridine derivative. (C) 2003 Elsevier Science Ltd. All rights reserved.
• 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.