6-乙基-3-[[4-[4-(4-甲基-1-哌嗪基)-1-哌啶基]苯基]氨基]-5-[[(3R)-1-(1-氧代-2-丙烯-1-基)-3-吡咯烷基]氧基]-2-吡嗪甲酰胺 | 1448232-80-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 6-乙基-3-[[4-[4-(4-甲基-1-哌嗪基)-1-哌啶基]苯基]氨基]-5-[[(3R)-1-(1-氧代-2-丙烯-1-基)-3-吡咯烷基]氧基]-2-吡嗪甲酰胺
• 英文名称: naquotinib
• 英文别名: ASP8273；Naquotinib；6-ethyl-3-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]oxypyrazine-2-carboxamide
• CAS: 1448232-80-1
• 化学式: C₃₀H₄₂N₈O₃
• 分子量: 562.715
• InChiKey: QKDCLUARMDUUKN-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  9

文献信息

• PYRAZINECARBOXAMIDE COMPOUND
  申请人：ASTELLAS PHARMA INC.

  公开号：US20140323463A1

  公开（公告）日：2014-10-30

  [Problem] A compound which is useful as an inhibitor on EGFR T790M mutation kinase activity is provided. [Means for Solution] The present inventors have investigated a compound having an inhibitory action on an EGFR T790M mutation kinase, and have found that a pyrazinecarboxamide compound has an inhibitory action on an EGFR T790M mutation kinase, thereby completing the present invention. The pyrazinecarboxamide compound of the present invention has an inhibitory action on an EGFR T790M mutation kinase, and can be used as an agent for preventing and/or treating EGFR T790M mutation positive cancer, in another embodiment, EGFR T790M mutation positive lung cancer, in a still other embodiment, EGFR T790M mutation positive non-small cell lung cancer, in further still another embodiment, EGFR T790M mutation protein positive cancer, in further still another embodiment, EGFR T790M mutation protein positive lung cancer, in further still another embodiment, EGFR tyrosine kinase inhibitor-resistant cancer, in further still another embodiment, EGFR tyrosine kinase inhibitor-resistant lung cancer, and in further still another embodiment, EGFR tyrosine kinase inhibitor-resistant non-small cell lung cancer, or the like.

  提供一种作为EGFR T790M突变激酶活性抑制剂的化合物。 解决方案的手段 本发明人调查了一种对EGFR T790M突变激酶具有抑制作用的化合物，并发现吡嗪羧酰胺化合物对EGFR T790M突变激酶具有抑制作用，从而完成了本发明。本发明的吡嗪羧酰胺化合物对EGFR T790M突变激酶具有抑制作用，并可用作预防和/或治疗EGFR T790M突变阳性癌症的药剂，在另一实施例中，EGFR T790M突变阳性肺癌，在另一实施例中，EGFR T790M突变阳性非小细胞肺癌，在进一步的另一实施例中，EGFR T790M突变蛋白阳性癌症，在进一步的另一实施例中，EGFR T790M突变蛋白阳性肺癌，在进一步的另一实施例中，EGFR酪氨酸激酶抑制剂耐药癌症，在进一步的另一实施例中，EGFR酪氨酸激酶抑制剂耐药肺癌，在进一步的另一实施例中，EGFR酪氨酸激酶抑制剂耐药非小细胞肺癌等。
• PYRAZINE CARBOXAMIDE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP2805940A1

  公开（公告）日：2014-11-26

  [Problem] A compound which is useful as an inhibitor on EGFR T790M mutation kinase activity is provided. [Means for Solution] The present inventors have investigated a compound having an inhibitory action on an EGFR T790M mutation kinase, and have found that a pyrazinecarboxamide compound has an inhibitory action on an EGFR T790M mutation kinase, thereby completing the present invention. The pyrazinecarboxamide compound of the present invention has an inhibitory action on an EGFR T790M mutation kinase, and can be used as an agent for preventing and/or treating EGFR T790M mutation positive cancer, in another embodiment, EGFR T790M mutation positive lung cancer, in a still other embodiment, EGFR T790M mutation positive non-small cell lung cancer, in further still another embodiment, EGFR T790M mutation protein positive cancer, in further still another embodiment, EGFR T790M mutation protein positive lung cancer, in further still another embodiment, EGFR tyrosine kinase inhibitor-resistant cancer, in further still another embodiment, EGFR tyrosine kinase inhibitor-resistant lung cancer, and in further still another embodiment, EGFR tyrosine kinase inhibitor-resistant non-small cell lung cancer, or the like.

  问题 提供一种可作为表皮生长因子受体（EGFR）T790M突变激酶活性抑制剂的化合物。 [解决方法］ 本发明人研究了一种对表皮生长因子受体T790M突变激酶具有抑制作用的化合物，发现一种吡嗪甲酰胺化合物对表皮生长因子受体T790M突变激酶具有抑制作用，从而完成了本发明。本发明的吡嗪甲酰胺化合物对表皮生长因子受体（EGFR）T790M突变激酶具有抑制作用，可用作预防和/或治疗表皮生长因子受体（EGFR）T790M突变阳性癌症的药物，在另一个实施方案中，可用作预防和/或治疗表皮生长因子受体（EGFR）T790M突变阳性肺癌的药物，在另一个实施方案中，可用作预防和/或治疗表皮生长因子受体（EGFR）T790M突变阳性非小细胞肺癌的药物，在更进一步的另一个实施方案中，可用作预防和/或治疗表皮生长因子受体（EGFR）T790M突变阳性非小细胞肺癌的药物、表皮生长因子受体（EGFR）T790M突变蛋白阳性癌症，在更进一步的仍是另一个实施方案中，表皮生长因子受体（EGFR）T790M突变蛋白阳性肺癌，在更进一步的仍是另一个实施方案中，表皮生长因子受体（EGFR）酪氨酸激酶抑制剂耐药癌症，在更进一步的仍是另一个实施方案中，表皮生长因子受体（EGFR）酪氨酸激酶抑制剂耐药肺癌，在更进一步的仍是另一个实施方案中，表皮生长因子受体（EGFR）酪氨酸激酶抑制剂耐药非小细胞肺癌，或类似物。
• MEDICINAL COMPOSITION COMPRISING PYRAZINE CARBOXAMIDE COMPOUND AS ACTIVE INGREDIENT
  申请人：Astellas Pharma Inc.

  公开号：EP3150206A1

  公开（公告）日：2017-04-05

  [Problem] Provided is a pharmaceutical composition for treating cancer in which one or more kinases of BTK, JAK3, and ITK is involved. [Means for Solution] The present inventors studied compounds having a BTK inhibiting effect, a JAK3 inhibiting effect and an ITK inhibiting effect, and confirmed that a specific pyrazine carboxamide compound has the BTK inhibiting effect, the JAK3 inhibiting effect, and the ITK inhibiting effect, and that a pharmaceutical composition comprising the compound as an active ingredient has a therapeutic effect on cancer in which one or more kinases of BTK, JAK3 and ITK is involved, in another aspect, cancer in which BTK is overexpressed or activated, in another aspect, cancer in which a B cell receptor signal is activated, in still another aspect, cancer in which JAK3 is activation-mutated or activated, and in still another aspect, cancer in which ITK is activated, thereby completing the present invention.

  问题 本发明提供了一种用于治疗癌症的药物组合物，该药物组合物涉及BTK、JAK3和ITK中的一种或多种激酶。 [解决方法］ 本发明人研究了具有 BTK 抑制作用、JAK3 抑制作用和 ITK 抑制作用的化合物，证实特定的吡嗪羧酰胺化合物具有 BTK 抑制作用、JAK3 抑制作用和 ITK 抑制作用，并且包含该化合物作为有效成分的药物组合物对 BTK 的一种或多种激酶参与的癌症具有治疗效果、JAK3和ITK的一种或多种激酶参与的癌症具有治疗效果，在另一个方面，BTK过表达或被激活的癌症，在另一个方面，B细胞受体信号被激活的癌症，在还有一个方面，JAK3活化突变或被激活的癌症，以及在还有一个方面，ITK被激活的癌症，从而完成了本发明。
• STABILIZED PHARMACEUTICAL COMPOSITION
  申请人：Astellas Pharma Inc.

  公开号：EP3290036A1

  公开（公告）日：2018-03-07

  Provided is a pharmaceutical composition, which comprises 5-[(3R)-1-acryloylpyrrolidin-3-yl]oxy}-6-ethyl-3-(4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-pyrazine-2-carboxamide (hereinafter referred to as "compound A") or a pharmaceutically acceptable salt thereof, and is stabilized. The pharmaceutical composition comprises compound A or a pharmaceutically acceptable salt thereof, and a pharmaceutical additive having a difference in water activity value of 0.1 or more, and is stabilized.

  本发明提供了一种药物组合物，它包含 5-[(3R)-1-丙烯酰基吡咯烷-3-基]氧基}-6-乙基-3-(4-[4-(4-甲基哌嗪-1-基)哌啶-1-基]苯基}氨基)-吡嗪-2-甲酰胺（以下简称 "化合物 A"）或其药学上可接受的盐，并已稳定。该药物组合物包含化合物 A 或其药学上可接受的盐，以及水活性值相差 0.1 或更多的药物添加剂，并已稳定。
• STABLE PHARMACEUTICAL COMPOSITION
  申请人：Astellas Pharma Inc.

  公开号：EP3533448A1

  公开（公告）日：2019-09-04

  Provided is a pharmaceutical composition, which comprises 5-[(3R)-1-acryloylpyrrolidin-3-yl]oxy}-6-ethyl-3-(4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-pyrazine-2-carboxamide or a pharmaceutically acceptable salt thereof, and is stabilized. The pharmaceutical composition comprises potassium chloride and/or sodium chloride, and inhibits the increase of related substances.

  本发明提供了一种药物组合物，它包含 5-[(3R)-1-丙烯酰基吡咯烷-3-基]氧基}-6-乙基-3-(4-[4-(4-甲基哌嗪-1-基)哌啶-1-基]苯基}氨基)-吡嗪-2-甲酰胺或其药学上可接受的盐，并经过稳定化处理。该药物组合物包含氯化钾和/或氯化钠，可抑制相关物质的增加。