2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide | 352227-91-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide
• 英文别名: 2-[(Pyridin-6(1H)-on-3-yl)methyl]amino-N-[3-(trifluoromethyl)phenyl]-3-pyridinecarboxamide；3-Pyridinecarboxamide, 2-(((1,6-dihydro-6-oxo-3-pyridinyl)methyl)amino)-N-(3-(trifluoromethyl)phenyl)-；2-[(6-oxo-1H-pyridin-3-yl)methylamino]-N-[3-(trifluoromethyl)phenyl]pyridine-3-carboxamide
• CAS: 352227-91-9
• 化学式: C₁₉H₁₅F₃N₄O₂
• 分子量: 388.349
• InChiKey: NINCSGUFEFCKJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  83.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-[(6-Methoxy-3-pyridyl)methyl]amino-N-[3-(trifluoromethyl)phenyl]-3-pyridinecarboxamide 、 碘代三甲硅烷 、 甲醇 在 氨 、 乙酸乙酯 、 氯化钠 、 Sodium sulfate-III 、 crude product 作用下， 以 氯仿 为溶剂， 反应 28.17h， 生成 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide
  参考文献：
  名称：

  2-amino-nicotinamide derivatives and their use as VEGF-receptor tyrosine kinase inhibitors

  摘要：

  本发明涉及使用式I的2-氨基烟酰胺衍生物，其中n为1至6（含1和6）；W为O或S；R1和R3分别独立表示氢、低级烷基或低级酰基；R2表示环烷基、芳基或含有一个或多个环氮原子和0、1或2个异原子（选自氧和硫）的单环或双环杂芳基，上述基团均未取代或单取代或多取代；R和R′分别独立表示氢或低级烷基；X表示芳基或含有一个或多个环氮原子和0、1或2个异原子（选自氧和硫）的单环或双环杂芳基，上述基团均未取代或单取代或多取代；或者其N-氧化物、可能的互变异构体或其药学上可接受的盐，单独或与一种或多种其他药物活性化合物联合使用，用于制备用于治疗对VEGF受体酪氨酸激酶活性抑制有反应的疾病的药物组合物；以及式I的新2-氨基烟酰胺衍生物及其制备方法。

  公开号：

  US06624174B2

文献信息

• METHOD FOR ASSAY ON THE EFFECT OF VASCULARIZATION INHIBITOR
  申请人：Uenaka Toshimitsu

  公开号：US20100092490A1

  公开（公告）日：2010-04-15

  The present invention provides a method of predicting the antitumor effect of an angiogenesis inhibitor. It is possible to predict the antitumor effect of an angiogenesis inhibitor by evaluating the EGF dependency of a tumor cell for proliferation and/or survival and using the EGF dependency as an indicator. Since the antitumor effect of an angiogenesis inhibitor correlates with the EGF dependency of a tumor cell for proliferation and/or survival, the angiogenesis inhibitors is capable of producing excellent antitumor effect when combined with a substance having EGF inhibitory activity.

  本发明提供了一种预测抗血管生成抑制剂的抗肿瘤效果的方法。通过评估肿瘤细胞对表皮生长因子（EGF）增殖和/或存活的依赖性，并将其作为指标，可以预测抗血管生成抑制剂的抗肿瘤效果。由于抗血管生成抑制剂的抗肿瘤效果与肿瘤细胞对EGF增殖和/或存活的依赖性相关，因此当与具有EGF抑制活性的物质结合时，抗血管生成抑制剂能够产生出色的抗肿瘤效果。
• 2-Amino-nicotinamide derivatives and their use as vegf-receptor tyrosine kinase inhibitors
  申请人：——

  公开号：US20030032656A1

  公开（公告）日：2003-02-13

  The invention relates to the use of 2-amino-nicotinamide derivatives of formula (I) wherein n is from 1 up to and including 6; W is O or S; R 1 and R 3 represent independently of each other hydrogen, lower alkyl or lower acyl; R 2 represents a cycloalkyl group, an aryl group, or a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms and 0, 1 or 2 heteroatoms independently from each other selected from the group consisting of oxygen and sulfur, which groups in each case are unsubstituted or mono- or polysubstituted; R and R′ are independently of each other hydrogen or lower alkyl; X represents an aryl group, or a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms and 0, 1 or 2 heteroatoms independently from each other selected from the group consisting of oxygen and sulfur, which groups in each case are unsubstituted or mono- or polysubstituted; or a N-oxide, a possible tautomer thereof or a pharmaceutically acceptale salt of such a compound, alone or in combination with one or more other pharmaceutically active compounds for the preparation of a pharmaceutical composition for use for therapy of a disease which responds to an inhibition of the VEGF-receptor tyrosine kinase activity; and to new 2-amino-nicotinamide derivatives of formula (I) and processes for the preparation thereof. 1

  本发明涉及使用公式（I）中的2-氨基烟酰胺衍生物，其中n为1至6，包括1和6；W为O或S；R1和R3分别表示氢、低烷基或低酰基；R2表示环烷基、芳基或含有一个或多个环氮原子和0、1或2个异原子的单环或双环杂芳基，这些基团在每种情况下都未取代或单取代或多取代；R和R'独立地表示氢或低烷基；X表示芳基或含有一个或多个环氮原子和0、1或2个异原子的单环或双环杂芳基，这些基团在每种情况下都未取代或单取代或多取代；或其N-氧化物、可能的互变异构体或其药学上可接受的盐，单独或与一个或多个其他药物活性化合物结合，用于制备用于治疗对抗VEGF受体酪氨酸激酶活性的抑制有反应的疾病的制剂；以及公式（I）的新型2-氨基烟酰胺衍生物及其制备方法。
• [EN] 2-AMINO-NICOTINAMIDE DERIVATIVES AND THEIR USE AS VEGF-RECEPTOR TYROSINE KINASE INHIBITORS<br/>[FR] DERIVES DE 2-AMINO-NICOTINAMIDE ET LEUR UTILISATION COMME INHIBITEURS DE TYROSINE KINASE DU RECEPTEUR VEGF
  申请人：NOVARTIS AG

  公开号：WO2001055114A1

  公开（公告）日：2001-08-02

  The invention relates to the use of 2-amino-nicotinamide derivatives of formula (I) wherein n is from 1 up to and including 6; W is O or S; R1 and R3 represent independently of each other hydrogen, lower alkyl or lower acyl; R2 represents a cycloalkyl group, an aryl group, or a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms and 0, 1 or 2 heteroatoms independently from each other selected from the group consisting of oxygen and sulfur, which groups in each case are unsubstituted or mono- or polysubstituted; R and R' are independently of each other hydrogen or lower alkyl; X represents an aryl group, or a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms and 0, 1 or 2 heteroatoms independently from each other selected from the group consisting of oxygen and sulfur, which groups in each case are unsubstituted or mono- or polysubstituted; or a N-oxide, a possible tautomer thereof or a pharmaceutically acceptale salt of such a compound, alone or in combination with one or more other pharmaceutically active compounds for the preparation of a pharmaceutical composition for use for therapy of a disease which responds to an inhibition of the VEGF-receptor tyrosine kinase activity; and to new 2-amino-nicotinamide derivatives of formula (I) and processes for the preparation thereof.

  本发明涉及使用式(I)的2-氨基烟酰胺衍生物，其中n为1至6，包括1和6；W为O或S；R1和R3各自独立地表示氢、低级烷基或低级酰基；R2表示环烷基、芳基或含有一个或多个环氮原子和0、1或2个异原子的单环或双环杂芳基，所述异原子独立地选自氧和硫的群，每种基团都未取代或单取代或多取代；R和R'各自独立地表示氢或低级烷基；X表示芳基或含有一个或多个环氮原子和0、1或2个异原子的单环或双环杂芳基，所述异原子独立地选自氧和硫的群，每种基团都未取代或单取代或多取代；或其N-氧化物，其可能的互变异构体或其药学上可接受的盐，单独或与一种或多种其他药物活性化合物结合，用于制备用于治疗对VEGF受体酪氨酸激酶活性抑制有反应的疾病的药物组合物；以及式(I)的新2-氨基烟酰胺衍生物及其制备方法。
• JOINT USE OF SULFONAMIDE BASED COMPOUND WITH ANGIOGENESIS INHIBITOR
  申请人：Eisai Co., Ltd.

  公开号：EP1797877A1

  公开（公告）日：2007-06-20

  The present invention relates to pharmaceutical compositions comprising a sulfonamide-including compound in combination with an angiogenesis inhibitor.

  本发明涉及药物组合物，其中包括磺胺类化合物与血管生成抑制剂的组合。
• METHOD FOR PREDICTION OF THE EFFICACY OF VASCULARIZATION INHIBITOR
  申请人：Eisai R&D Management Co., Ltd.

  公开号：EP1925941A1

  公开（公告）日：2008-05-28

  It is an object of the present invention to find out a method of predicting the antitumor effect of an angiogenesis inhibitor. According to the present invention, it is possible to predict the antitumor effect of an angiogenesis inhibitor by determining the number of those blood vessels which are covered with pericytes in a tumor and using the resultant number as an indicator.

  本发明的目的是找到一种预测血管生成抑制剂抗肿瘤效果的方法。根据本发明，可以通过确定肿瘤中被周细胞覆盖的血管的数量，并以该数量作为指标，来预测血管生成抑制剂的抗肿瘤效果。