6,7-dimethoxy-4-(3-hydroxyphenoxy)quinoline

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6,7-dimethoxy-4-(3-hydroxyphenoxy)quinoline
• 英文别名: 3-(6,7-Dimethoxy-quinolin-4-yloxy)-phenol；3-(6,7-dimethoxyquinolin-4-yl)oxyphenol
• 化学式: C₁₇H₁₅NO₄
• 分子量: 297.31
• InChiKey: CGIFTRWAYIWEGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6,7-二甲氧基-4-(3-乙酰氧基苯氧基)喹啉 在 potassium carbonate 作用下， 以 甲醇 、 氯仿 为溶剂， 以92%的产率得到6,7-dimethoxy-4-(3-hydroxyphenoxy)quinoline
  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 derivatives inhibiting the effect of growth factors such as VEGF
  申请人：Zeneca Limited

  公开号：US06809097B1

  公开（公告）日：2004-10-26

  Compounds of the formula (I): wherein: R2 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; n is an integer from 0 to 5; Z represents —O—, —NH—, —S— or —CH2—; G1 represents phenyl or a 5-10 membered heteroaromatic cyclic or bicyclic group; Y1, Y2, Y3 and Y4 each independently represents carbon or nitrogen; R1 represents fluoro or hydrogen; m is an integer from 1 to 3; R3 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR4R5 (wherein R4 and R5, can each be hydrogen or C1-3alkyl), or a group R6—X1— wherein X1 represents —CH2— or a heteroatom linker group and R6 is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R6 is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals such as humans, processes for the preparation of such derivatives, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

  公式(I)的化合物： 其中：R2代表羟基，卤素，C1-3烷基，C1-3烷氧基，C1-3烷酰氧基，三氟甲基，氰基，氨基或硝基；n是0到5之间的整数；Z代表—O—，—NH—，—S—或—CH2—；G1代表苯基或一个5-10员的杂芳环状或双环状基团；Y1、Y2、Y3和Y4各自独立代表碳或氮；R1代表氟或氢；m是1到3之间的整数；R3代表氢，羟基，卤素，氰基，硝基，三氟甲基，C1-3烷基，—NR4R5（其中R4和R5各自可以是氢或C1-3烷基），或一个R6—X1—基团，其中X1代表—CH2—或一个杂原子连接基团，R6是一个烷基、烯基或炔基链，该链可选地被例如羟基、氨基、硝基、烷基、环烷基、烷氧基烷基或一个可选地被取代的吡啶酮、苯基和杂环环取代，该烷基、烯基或炔基链可能含有一个杂原子连接基团，或者R6是一个可选地被取代的吡啶酮、苯基和杂环环，以及它们的盐，用于制造一种药物，用于在温血动物如人类中产生抗血管生成和/或降低血管通透性的效果，制备这类衍生物的过程，包含公式I的化合物或其药物可接受的盐作为活性成分的药物组合物，以及公式I的化合物。公式I的化合物及其药物可接受的盐抑制VEGF的效果，这一特性在治疗包括癌症和类风湿性关节炎在内的多种疾病状态中具有价值。
• 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。
• A novel series of 4-phenoxyquinolines: potent and highly selective inhibitors of PDGF receptor autophosphorylation
  作者：Kazuo Kubo、Toshiyuki Shimizu、Shin-ichi Ohyama、Hideko Murooka、Tsuyoshi Nishitoba、Shinichiro Kato、Yoshiko Kobayashi、Mikio Yagi、Toshiyuki Isoe、Kazuhide Nakamura、Tatsushi Osawa、Toshio Izawa

  DOI：10.1016/s0960-894x(97)10117-2

  日期：1997.12

  A novel series of 4-phenoxyquinolines, some of which showed potent and highly selective inhibitory activities for PDGF receptor autophosphorylation, was discovered. Interestingly, their structures were very similar to those of the selective inhibitors for EGF receptor autophosphorylation. (C) 1997 Elsevier Science Ltd.
• QUINOLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES INHIBITING AUTOPHOSPHORYLATION OF GROWTH FACTOR RECEPTOR ORIGINATING IN PLATELET AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP0860433B1

  公开（公告）日：2002-07-03
• QINOLINE DERIVATIVES INHIBITING THE EFFECT OF GROWTH FACTORS SUCH AS VEGF
  申请人：AstraZeneca AB

  公开号：EP0929526B1

  公开（公告）日：2005-07-27