2-[(pyridin-4-yl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide

• 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-[(pyridin-4-yl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide
• 英文别名: AAL993；2-[(4-pyridyl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide；2-(pyridin-4-ylmethylamino)-N-[3-(trifluoromethyl)phenyl]benzamide
• 化学式: C₂₀H₁₆F₃N₃O
• 分子量: 371.362
• InChiKey: BLAFVGLBBOPRLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  54
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  间氯过氧苯甲酸 、 2-[(pyridin-4-yl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide 在 sodium hydroxide 、 disodium;dioxido-oxo-sulfanylidene-λ6-sulfane 、 Sodium sulfate-III 、 crude product 、 silica gel 、 eluent 、 乙醇 、 乙酸乙酯 、 ethyl acetate n-hexane 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以to give the title compound as a colourless crystalline solid, m.p. 181–184° C.的产率得到2-[(1-oxido-4-pyridyl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide
  参考文献：
  名称：

  N-aryl (thio) anthranilic acid amide derivatives, their preparation and their use as VEGF receptor tyrosine kinase inhibitors

  摘要：

  本文描述了式(I)的化合物，其中W为O或S；X为NR8；Y为CR9R10—(CH2)n，其中R9和R10独立地为氢或低碳基，n为0至3的整数，或Y为SO2；R1为芳基；R2为一个单环或双环杂芳基，其中包含一个或多个环氮原子，但R2不能代表2-苯酰亚胺基，且在Y=SO2的情况下不能代表2,1,3-苯并噻二唑-4-基；R3、R4、R5和R6中的任意一个，独立于其他的，为H或除氢以外的取代基；且R7和R8独立地为H或低碳基；或其N-氧化物或药学上可接受的盐，用于制备治疗对VEGF受体酪氨酸激酶活性抑制有反应的肿瘤疾病的药物产品。式(I)的化合物可用于治疗肿瘤疾病，如肿瘤疾病、视网膜病变和老年性黄斑变性等。

  公开号：

  US20030064992A1
• 作为产物：
  描述：

  2-氨基-N-[3-(三氟甲基)苯基]苯甲酰胺 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 2-[(pyridin-4-yl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide
  参考文献：
  名称：

  邻氨基苯甲酰胺：一类新型的抗血管生成的VEGF受体激酶抑制剂。

  摘要：

  已经制备了两种易于合成的邻氨基苯甲酰胺，VEGF受体酪氨酸激酶抑制剂，并将其评估为血管生成抑制剂。2-[（4-吡啶基）甲基]氨基-N- [3-（三氟甲基）苯基]苯甲酰胺（5）和N-3-异喹啉基-2-[（4-吡啶基甲基）氨基]苯甲酰胺（7）抑制重组VEGFR-2和VEGFR-3激酶。由于其物理化学性质，这些邻氨基苯甲酰胺很容易穿透细胞，并且在每天一次口服给小鼠后被吸收。在植入模型中，5和7均能有效抑制VEGF诱导的血管生成，ED（50）值为7 mg / kg。在黑色素瘤的小鼠原位模型中，5和7能有效抑制原发性肿瘤的生长以及自发性外周转移的形成。

  DOI：

  10.1021/jm020899q

文献信息

• N-aryl(thio)anthranilic acid amide derivatives, their preparation and their use as VEGF receptor tyrosine kinase inhibitors
  申请人：——

  公开号：US20020019414A1

  公开（公告）日：2002-02-14

  1 Described are compounds of formula (I), wherein W is O or S; X is NR 8 ; Y is CR 9 R 10 -(CH 2 )n wherein R 9 and R 10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO 2 ; R 1 is aryl; R 2 is a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms with the exception that R 2 cannot represent 2-phthalimidyl, and in case of Y═SO 2 cannot represent 2,1,3-benzothiadiazol-4-yl; any of R 3 , R 4 , R 5 and R 6 , independently of the other, is H or a substituent other than hydrogen; and R 7 and R 8 , independently of each other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.

  描述的是化合物的结构式（I），其中W是O或S；X是NR8；Y是CR9R10-(CH2)n，其中R9和R10彼此独立地是氢或较低的烷基，n是从0到3的整数；或Y是SO2；R1是芳基；R2是一个含有一个或多个环氮原子的单环或双环杂环基团，但R2不能代表2-邻苯二甲酰胺，并且在Y为SO2的情况下不能代表2,1,3-苯并噻二唑-4-基；R3、R4、R5和R6中的任何一个，独立于其他，是H或除氢之外的取代基；R7和R8，彼此独立地是H或较低的烷基；或其N-氧化物或药用可接受的盐，用于制备用于治疗对VEGF受体酪氨酸激酶活性抑制产生反应的恶性疾病的药物产品。结构式（I）的化合物可用于治疗恶性疾病，如肿瘤疾病，视网膜病和老年性黄斑变性等。
• Discovery of Potent Vascular Endothelial Growth Factor Receptor-2 Inhibitors
  作者：Athanasios Papakyriakou、Maria E. Katsarou、Maria Belimezi、Michael Karpusas、Dionisios Vourloumis

  DOI：10.1002/cmdc.200900373

  日期：2010.1.4

  states, including cancer. Vascular endothelial growth factor (VEGF) plays a critical role in its regulation. Because the tyrosine kinase VEGF receptor‐2 (VEGFR‐2) is the major mediator of the mitogenic, angiogenic, and permeability‐enhancing effects of VEGF, it has become one of the most profound anti‐angiogenesis targets. Inspired by the anthranilamide class of VEGFR‐2 inhibitors, we performed a computational

  在过去的几十年中，大量证据表明血管生成不受控制，并伴有多种病理状态，包括癌症。血管内皮生长因子（VEGF）在其调节中起关键作用。由于酪氨酸激酶VEGF受体2（VEGFR-2）是VEG​​F促有丝分裂，促血管生成和通透性增强作用的主要介质，因此它已成为最深刻的抗血管生成靶标之一。受蒽环酰胺类VEGFR-2抑制剂的启发，我们使用对接和分子动力学计算方法对一些有效的代表性成员进行了计算分析。基于引入受体在隐性水环境中的柔韧性影响而得出的观察结果，我们设计，合成，并表征了几种相关支架的新类似物，并对其空间和电子特性进行了修改。这些化合物的体外评估显示了几种新型VEGFR-2抑制剂，它们比母体化合物具有更低的细胞毒性和更强的毒性。
• [EN] N-ARYL(THIO)ANTHRANILIC ACID AMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS VEGF RECEPTOR TYROSINE KINASE INHIBITORS<br/>[FR] DERIVES DE N-ARYL(THIO)ANTHRANILIQUE ACIDE AMIDE, LEUR PREPARATION ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA TYROSINE KINASE DU RECEPTEUR VEGF
  申请人：NOVARTIS AG

  公开号：WO2000027820A1

  公开（公告）日：2000-05-18

  Described are compounds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10-(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO2; R1 is aryl; R2 is a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms with the exception that R2 cannot represent 2-phthalimidyl, and in case of Y = SO2 cannot represent 2,1,3-benzothiadiazol-4-yl; any of R3, R4, R5 and R6, independently of the other, is H or a substituent other than hydrogen; and R7 and R8, independently of each other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.

  本文描述了式(I)的化合物，其中W是O或S；X是NR8；Y是CR9R10-(CH2)n，其中R9和R10独立地是氢或低级烷基，n是0至3的整数；或者Y是SO2；R1是芳基；R2是一个含有一个或多个环氮原子的单环或双环杂环基团，但R2不能代表2-苯甲酰亚胺基，且在Y = SO2的情况下不能代表2,1,3-苯并噻二唑-4-基；R3、R4、R5和R6中的任何一个，除了氢之外，都是取代基；R7和R8独立地是氢或低级烷基；或其N-氧化物或药学上可接受的盐，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肿瘤疾病的制药产品。式(I)的化合物可用于治疗肿瘤疾病、视网膜病变和年龄相关性黄斑变性等疾病。
• N-aryl (THIO) anthranilic acid amide derivatives, their preparation and their use as VEGF receptor tyrosine kinase inhibitors
  申请人：——

  公开号：US20040198782A1

  公开（公告）日：2004-10-07

  1 Described are compunds of formula (I), wherein W is O or S; X is NR 8 ; Y is CR 9 R 10 —(CH 2 ) n wherein R 9 and R 10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO 2 ; R 2 is aryl; R 2 is a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms with the exception that R 2 cannot represent 2-phthalimidyl, and in case of Y=SO 2 cannot represent 2,1,3-benzothiadiazol-4-yl; any of R 3 , R 4 , R 5 and R 6 , independently of the other, is H or a substituent other than hydrogen; and R 7 and R 8 , independently of each other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.

  描述了化合物的公式(I)，其中W为O或S; X为NR8; Y为CR9R10—(CH2)n，其中R9和R10独立地为氢或低烷基，n为0至3的整数，包括0和3; 或Y为SO2; R2为芳基; R2为一种单环或双环杂环芳基，包括一个或多个环氮原子，但R2不能表示2-邻苯二甲酰亚胺基，且在Y = SO2的情况下不能表示2,1,3-苯并噻二唑-4-基; R3、R4、R5和R6中的任何一个，除了氢之外，都是取代基; R7和R8独立地为氢或低烷基; 或其N-氧化物或药学上可接受的盐，用于制备治疗对VEGF受体酪氨酸激酶活性抑制有反应的肿瘤疾病的制药产品。公式(I)的化合物可用于治疗肿瘤疾病，如肿瘤疾病，视网膜病和年龄相关性黄斑变性等。
• VEGF receptor tyrosine kinase inhibitors
  申请人：Novartis AG

  公开号：US06448277B2

  公开（公告）日：2002-09-10

  Described are compounds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10—(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is S02; R1 is aryl; R2 is a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms with the exception that R2 cannot represent 2-phthalimidyl, and in case of Y=SO2 cannot represent 2,1,3-benzothiadiazol-4-yl; any of R3, R4, R5 and R6, independently of the other, is H or a substituent other than hydrogen; and R7 and R8, independently of each other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.

  本文描述了式（I）的化合物，其中W为O或S；X为NR8；Y为CR9R10—（CH2）n，其中R9和R10独立地为氢或低烷基，n为0至3的整数，包括0和3；或Y为S02；R1为芳基；R2为单环或双环杂芳基，包括一个或多个环氮原子，但R2不能表示2-邻苯二甲酰亚胺基，且在Y = SO2的情况下不能表示2,1,3-苯并噻二唑-4-基；R3、R4、R5和R6中的任何一个独立地为H或除氢原子以外的取代基；R7和R8独立地为H或低烷基；或其N-氧化物或药学上可接受的盐，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肿瘤性疾病的制药产品。式（I）的化合物可用于治疗肿瘤性疾病，例如肿瘤疾病，视网膜病变和年龄相关性黄斑变性等。