3-(methoxy)pyrazine-2-carboxamide | 21279-63-0

• 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: 3-(methoxy)pyrazine-2-carboxamide
• 英文别名: 3-Methoxy-2-carbamoyl-pyrazin；2-Carboxyamido-3-methoxypyrazin；3-methoxy-pyrazine-2-carboxylic acid amide；3-Methoxy-2-pyrazinecarboxamide；3-methoxypyrazine-2-carboxamide
• CAS: 21279-63-0
• 化学式: C₆H₇N₃O₂
• 分子量: 153.14
• InChiKey: LZYQFKPLSBGGTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  78.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(methoxy)pyrazine-2-carboxamide 在 双氧水 、 溶剂黄146 作用下， 反应 6.0h， 生成 3-Methoxy-pyrazin-4-oxid-2-carbonsaeureamid
  参考文献：
  名称：

  Ambrogi; Cozzi; Sanjust, European Journal of Medicinal Chemistry, 1980, vol. 15, # 2, p. 157 - 163

  摘要：

  DOI：
• 作为产物：
  描述：

  3-甲氧基吡嗪-2-甲腈 在 硫酸 、 三氟乙酸 作用下， 以85 %的产率得到3-(methoxy)pyrazine-2-carboxamide
  参考文献：
  名称：

  在离子液体中从 Selectfluor® 和 3-hydroxy-2-pyrazinecarboxamide 一步合成 favipiravir

  摘要：

  Favipiravir 是一种重要的选择性抗病毒药物，在大流行期间作为对抗 COVID-19 的替代药物出现。它的合成引起了极大的兴趣，传统的策略通过多步协议（6-7 个反应步骤）进行，此外，还涉及全球收率低于 34% 的几个缺点。在此，报道了一种简单、经济、环保和可扩展的 (1 g) 一步法方案，用于通过使用 Selectfluor® 直接氟化可用的 3-羟基-2-吡嗪甲酰胺来合成法匹拉韦。通过简单的操作后处理，该反应在 BF 4 -BMIM 中很容易进行，无需特殊催化剂/添加剂即可获得产率为 50% 的法匹拉韦。本战略的重点是使用BF 4离子液体-BMIM，这有助于最大限度地减少源自 3-hydroxy-2-pyrazinecarboxamide 作为直接 Selectfluor 介导的氟化底物的几种化学限制。还详细讨论了所有这些化学反应性方面。

  DOI：

  10.1039/d3ob00380a

文献信息

• AMINO-DIHYDROTHIAZINE AND AMINO-DIOXIDO DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE ANTAGONISTS AND METHODS OF USE
  申请人：Amgen Inc.

  公开号：US20140107109A1

  公开（公告）日：2014-04-17

  The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A 4 , A 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-II.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物具有一般的化学式I： 其中化学式I中的变量A4、A5、A6、A8、R1、R2、R3、R7和n在此独立地被定义。该发明还提供了包含这些化合物的药物组合物，以及这些化合物和组合物用于治疗与A-beta斑块形成和沉积相关的疾病和/或症状的对应用途，这些疾病和症状是由BACE的生物活性引起的。这种由BACE介导的疾病包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他中枢神经系统疾病。该发明还提供了化学式II的化合物及其亚式化合物，中间体和用于制备化学式I-II化合物的有用过程和方法。
• [EN] AMINO-OXAZINES AND AMINO-DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE<br/>[FR] COMPOSÉS D'AMINO-OXAZINES ET D'AMINO-DIHYDROTHIAZINE COMME MODULATEURS DE SÉCRÉTASE BÊTA ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2013044092A1

  公开（公告）日：2013-03-28

  The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, L, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一类新的化合物，用于调节β-分泌酶酶活性，并用于治疗β-分泌酶介导的疾病，包括阿尔茨海默病（AD）及相关病症。在一个实施例中，这些化合物具有一般的化学式I，其中化学式I中的A1、A2、A3、A4、A5、A6、L、R2、R7、X、Y和Z在此处定义。该发明还包括将这些化合物用于制备用于治疗与β-分泌酶蛋白活性相关的疾病和病症的药物组合物，包括例如阿尔茨海默病、认知缺陷、认知障碍、精神分裂症以及与大脑斑块的形成和/或沉积相关的其他中枢神经系统病症。该发明还涉及化学式I的进一步实施例、中间体和用于制备化合物的有用过程。
• [EN] C5-C6-CARBOCYCLIC FUSED IMINOTHIADIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE<br/>[FR] DIOXYDES D'IMINOTHIADIAZINE CARBOXYLIQUES EN C5-C6 CONDENSÉS UTILISÉS COMME INHIBITEURS DE BACE, COMPOSITIONS, ET UTILISATION ASSOCIÉE
  申请人：MERCK SHARP & DOHME

  公开号：WO2017095759A1

  公开（公告）日：2017-06-08

  In its many embodiments, the present invention provides certain C5-C6-carbocyclic fused iminothiazine dioxide compounds, including compounds Formula (I): and tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1, ring A, RA, m, -L1-, ring B, RB, n, q, ring C, RC, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

  在其许多实施方式中，本发明提供了某些C5-C6-环融合咪唑硫酸亚胺二氧化物化合物，包括化合物式（I）：及其互变异构体，以及所述化合物和所述互变异构体的药学上可接受的盐，其中R1、环A、RA、m、-L1-、环B、RB、n、q、环C、RC和p的定义如本文所述。本发明的新化合物可用作BACE抑制剂和/或用于治疗和预防与之相关的各种病理。还公开了包括一种或多种此类化合物（单独和与一种或多种其他活性剂的组合）的药物组合物，以及其制备和使用方法，包括可能用于治疗阿尔茨海默病的方法。
• Process for preparing alkoxypyrazine derivatives
  申请人：——

  公开号：US20010012894A1

  公开（公告）日：2001-08-09

  A process for preparing alkoxypyrazine derivatives of the general formula: 1 These alkoxypyrazine derivatives are obtained by reacting a glyoxal derivative of the general formula: 2 and an amimoimidate of the general formula: 3 The alkoxypyrazine derivatives are important intermediates for preparing pharmaceutically active compounds.

  一种制备通式为1的烷氧基吡嗪衍生物的方法：这些烷氧基吡嗪衍生物是通过将通式为2的丙二醛衍生物和通式为3的氨基咪唑酸盐反应得到的。这些烷氧基吡嗪衍生物是制备药物活性化合物的重要中间体。
• Compositions For Treating Flushing And Lipid-Associated Disorders Comprising Niacin Receptor Partial Agonists
  申请人：Behan Dominic P.

  公开号：US20080139628A1

  公开（公告）日：2008-06-12

  The invention provides a method of reducing flushing induced by niacin or a niacin analog in a subject, comprising administering to said subject an effective flush reducing amount of a niacin receptor partial agonist. In addition, the invention provides a method of reducing flushing induced by niacin or a niacin analog in a subject, comprising administering to said subject an effective flush reducing amount of a niacin receptor partial agonist and an effective lipid altering amount of niacin or a niacin analog. The invention further provides a method of reducing flushing induced by niacin or a niacin analog in a subject, comprising administering to said subject an effective flush reducing amount of a niacin receptor partial agonist and subsequently administering to said subject an effective lipid altering amount of niacin or a niacin analog.

  本发明提供了一种减少烟酸或烟酸类似物引起的面红的方法，包括向该受体中注射有效减少面红量的烟酸受体部分激动剂。此外，本发明还提供了一种减少烟酸或烟酸类似物引起的面红的方法，包括向该受体中注射有效减少面红量的烟酸受体部分激动剂和有效改变脂质含量的烟酸或烟酸类似物。本发明进一步提供了一种减少烟酸或烟酸类似物引起的面红的方法，包括向该受体中注射有效减少面红量的烟酸受体部分激动剂，然后向该受体中注射有效改变脂质含量的烟酸或烟酸类似物。