Ki6896 | 190726-52-4

• 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: Ki6896
• 英文别名: [4-(Tert-butyl)phenyl]{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-methanone；[4-(tert-butyl)phenyl]{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}methanone；(4-t-butylphenyl){4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}methanone；(4-tert-butylphenyl)-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]methanone
• CAS: 190726-52-4
• 化学式: C₂₈H₂₇NO₄
• 分子量: 441.527
• InChiKey: IBXFZLDPLQETKT-UHFFFAOYSA-N

物化性质

• 沸点：
  585.1±50.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  57.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ki6896 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以97%的产率得到(4-tert-butylphenyl)-[4-(6,7-dimethoxy-4-quinolyloxy)phenyl]methanol
  参考文献：
  名称：

  EP1447405

  摘要：

  公开号：
• 作为产物：
  描述：

  4-羟基-6,7-二甲氧基喹啉 在 三氯氧磷 作用下， 反应 1.17h， 生成 Ki6896
  参考文献：
  名称：

  Synthesis and structure–activity relationship for new series of 4-Phenoxyquinoline derivatives as specific inhibitors of platelet-derived growth factor receptor tyrosine kinase

  摘要：

  We discovered a new series of 4-phenoxyquinoline derivatives as potent and selective inhibitors of the platelet-derived growth factor receptor (PDGFr) tyrosine kinase. We researched the highly potent and selective inhibitors on the basis of both PDGFr and epidermal growth factor receptor (EGFr) inhibitory activity. First, we found a compound, Ki6783 (1), which inhibited PDGFr autophosphorylation at 0.13 muM, but it did not inhibit EGFr autophosphorylation at 100 muM. After extensive explorations, we found the two desired compounds, Ki6896 (2) and Ki6945 (3), which are substituted by benzoyl and benzamide at the 4-position of the phenoxy group on 4-phenoxyquinoline, respectively. These inhibitory activities were 0.31 and 0.050 muM, respectively, but neither of them inhibited EGFr autophosphorylation at 100 M. We further investigated the profile of both compounds toward various tyrosine and serine/threonine kinases. The three compounds specifically inhibited PDGFr rather than the other kinases. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.08.020

文献信息

• Quinoline and quinazoline derivatives inhibiting platelet-derived growth
  申请人：Kirin Beer Kabushiki Kaisha

  公开号：US06143764A1

  公开（公告）日：2000-11-07

  The present invention relates to novel quinoline derivatives and quinazoline derivatives represented by the following formula (I): ##STR1## [wherein R.sub.1 and R.sub.2 are each independently H or C.sub.1 -C.sub.4 -alkyl, or R.sub.1 and R.sub.2 together form C.sub.1 -C.sub.3 -alkylene, X is O, S or CH.sub.2, W is CH or N, and Q is a substituted aryl group or substituted heteroaryl group] and their pharmaceutically acceptable salts, having platelet-derived growth factor receptor autophosphorylation inhibitory activity, to pharmaceutical compositions containing these compounds, and to methods for the treatment of diseases associated with abnormal cell growth such as tumors.

  本发明涉及由以下式（I）表示的新型喹啉衍生物和喹唑啉衍生物：[其中R.sub.1和R.sub.2分别独立地为H或C.sub.1 -C.sub.4 -烷基，或R.sub.1和R.sub.2一起形成C.sub.1 -C.sub.3 -烷基，X为O、S或CH.sub.2，W为CH或N，Q为取代芳基或取代杂芳基]及其在药学上可接受的盐，具有血小板源性生长因子受体自磷酸化抑制活性，用于含有这些化合物的药物组合物，以及用于治疗与异常细胞生长（如肿瘤）相关的疾病的方法。
• 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。
• Quinoline or quinazoline derivatives inhibiting auto-phosphorylation of fibroblast growth factor receptors
  申请人：Miwa Atsushi

  公开号：US20050049264A1

  公开（公告）日：2005-03-03

  An objective of the present invention is to provide novel compounds which have inhibitory activity against autophosphorylation of an FGF receptor family and, when orally or intraveneously administered, can suppress the growth of cancer cells. The compounds of the present invention are represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein X represents CH or N; Z represents O or S; Q represents NR 10 , CR 11 R 2 , carbonyl, O, S(═O)m, wherein m is 0 to 2, or urea; R 1 to R 3 each independently represent H, OH, halogen, nitro, amino, alkyl, alkoxy or the like in which the alkyl and alkoxy groups are optionally substituted; R 4 represents H; R 5 to R 8 each independently represent H, halogen, alkyl, or alkoxy; and R 9 represents an optionally substituted carbocyclic or heterocyclic group.

  本发明的目标是提供新型化合物，其具有对FGF受体家族自磷酸化的抑制活性，并在口服或静脉注射时能够抑制癌细胞的生长。本发明的化合物由公式（I）或其药学上可接受的盐或溶剂表示：其中X代表CH或N; Z代表O或S; Q代表NR10，CR11R2，羰基，O，S（═O）m，其中m为0到2，或脲基; R1至R3各自独立地表示H、OH、卤素、硝基、氨基、烷基、烷氧基或其类似物，其中烷基和烷氧基基团可选择性地被取代; R4表示H; R5至R8各自独立地表示H、卤素、烷基或烷氧基; R9表示一个可选择性取代的碳环或杂环基团。
• QUINOLINE OR QUINAZOLINE DERIVATIVES INHIBITING AUTO-PHOSPHORYLATION OF FIBROBLAST GROWTH FACTOR RECEPTORS
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP1447405A1

  公开（公告）日：2004-08-18

  An objective of the present invention is to provide novel compounds which have inhibitory activity against autophosphorylation of an FGF receptor family and, when orally or intraveneously administered, can suppress the growth of cancer cells. The compounds of the present invention are represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein X represents CH or N; Z represents 0 or S; Q represents NR10, CR11R12, carbonyl, O, S(=O)m, wherein m is 0 to 2, or urea; R1 to R3 each independently represent H, OH, halogen, nitro, amino, alkyl, alkoxy or the like in which the alkyl and alkoxy groups are optionally substituted; R4 represents H; R5 to R8 each independently represent H, halogen, alkyl, or alkoxy; and R9 represents an optionally substituted carbocyclic or heterocyclic group.

  本发明的目的是提供对 FGF 受体家族的自身磷酸化具有抑制活性的新型化合物，口服或静脉注射后可抑制癌细胞的生长。本发明的化合物由式（I）或其药学上可接受的盐或溶液表示： 其中 X 代表 CH 或 N；Z 代表 0 或 S；Q 代表 NR10、CR11R12、羰基、O、S(＝O)m（其中 m 为 0 至 2）或脲；R1 至 R3 各自独立地代表 H、OH、卤素、硝基、氨基、烷基、烷氧基或类似基团，其中烷基和烷氧基是任选取代的；R4 代表 H；R5 至 R8 各自独立地代表 H、卤素、烷基或烷氧基；R9 代表任选取代的碳环或杂环基团。
• 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。