1-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)phenyl)-3-phenylurea | 1256394-33-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)phenyl)-3-phenylurea
• 英文别名: 1-(4-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-phenylurea；1-[4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-phenylurea
• CAS: 1256394-33-8
• 化学式: C₂₃H₂₀N₄O₄
• 分子量: 416.436
• InChiKey: DHQJQTUHXYIGKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  94.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  异氰酸苯酯 在 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 1-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)phenyl)-3-phenylurea
  参考文献：
  名称：

  发现 BPR1R024，一种口服活性、选择性 CSF1R 抑制剂，在小鼠结肠肿瘤模型中表现出抗肿瘤和免疫调节活性

  摘要：

  集落刺激因子 1 受体 (CSF1R) 与肿瘤相关巨噬细胞 (TAM) 复极化有关，并已成为癌症免疫治疗的一个有前景的靶点。在此，我们描述了通过对我们的临床多靶点激酶抑制剂 BPR1K871 ( 9 ) 进行特性驱动优化来发现口服活性和选择性 CSF1R 抑制剂。分子对接揭示了独特的 7-氨基喹唑啉支架和 CSF1R 铰链区之间额外的非经典氢键 (NCHB) 相互作用，有助于 CSF1R 效力的增强。 CSF1R 和极光激酶 B (AURB) 的结构研究证明了它们后袋的差异，这启发了使用链延伸策略来减少 AURA/B 活性。先导化合物 BPR1R024 ( 12 ) 表现出强大的 CSF1R 活性 (IC 50 = 0.53 nM)，并特异性抑制促肿瘤 M2 样巨噬细胞的存活，而对抗肿瘤 M1 样巨噬细胞生长的影响最小。在体内，口服12甲磺酸盐可延缓MC38小鼠结肠肿瘤的生长，并通过增加M

  DOI：

  10.1021/acs.jmedchem.1c01006

文献信息

• Design, Synthesis, and DNA-Binding of <i>N</i>-Alkyl(anilino)quinazoline Derivatives
  作者：Antonio Garofalo、Laurence Goossens、Brigitte Baldeyrou、Amélie Lemoine、Séverine Ravez、Perrine Six、Marie-Hélène David-Cordonnier、Jean-Paul Bonte、Patrick Depreux、Amélie Lansiaux、Jean-François Goossens

  DOI：10.1021/jm1009605

  日期：2010.11.25

  New N-alkylanilinoquinazoline derivatives 5, 12, 20, and 22 have been prepared Crow 4-chloro-6, 7-dimethoxyquinazoline 3, 4-chloro-6,7-methylenedioxyquinazoline 19, and commercially available anilines. Differents classes of compounds substituted by an aryloxygroup (6a-c. 16a,b, and 17a,b). (aminophenyl)ureas (12a,b and 13a-f), anilines (4a-m, 20a,b), N-alkyl(aniline) (5a-m, 21a,b. 22a,d). and N-aminoalkyl(aniline) (22e-g) have been synthesized. These molecules were evaluated for then. cytotoxic activities and as potential DNA intercalating agents. We studied the strength and mode of binding to DNA of these molecules by DNA melting temperature measurements, fluorescence emission. and circular dichroism. The results of various spectral and gel electrophoresis techniques obtained with the different compounds, in particular compounds 5g and 22f, revealed significant DNA interaction. These experiments confirm that the N-aminoalkyl(anilino)-6,7-dimethoxyquinazoline nucleus is an efficient pharmacophore to trigger binding to DNA, via an intercalative binding process.
• Impact of aryloxy-linked quinazolines: A novel series of selective VEGFR-2 receptor tyrosine kinase inhibitors
  作者：Antonio Garofalo、Laurence Goossens、Perrine Six、Amélie Lemoine、Séverine Ravez、Amaury Farce、Patrick Depreux

  DOI：10.1016/j.bmcl.2011.01.137

  日期：2011.4

  Three series of 6,7-dimethoxyquinazoline derivatives substituted in the 4-position by aniline, N-methylaniline and aryloxy entities, targeting EGFR and VEGFR-2 tyrosine kinases, were designed and synthesized. Pharmacological activities of these compounds have been evaluated for their enzymatic inhibition of VEGFR-2 and EGFR and for their antiproliferative activities on various cancer cell lines. We have studied the impact of the variation in the 4-position substitution of the quinazoline core. Substitution by aryloxy groups led to new compounds which are selective inhibitors of VEGFR-2 enzyme with IC50 values in the nanomolar range in vitro. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery of BPR1R024, an Orally Active and Selective CSF1R Inhibitor that Exhibits Antitumor and Immunomodulatory Activity in a Murine Colon Tumor Model
  作者：Kun-Hung Lee、Wan-Ching Yen、Wen-Hsing Lin、Pei-Chen Wang、You-Liang Lai、Yu-Chieh Su、Chun-Yu Chang、Cai-Syuan Wu、Yu-Chen Huang、Chen-Ming Yang、Ling-Hui Chou、Teng-Kuang Yeh、Chiung-Tong Chen、Chuan Shih、Hsing-Pang Hsieh

  DOI：10.1021/acs.jmedchem.1c01006

  日期：2021.10.14

  diminish the AURA/B activities. A lead compound BPR1R024 (12) exhibited potent CSF1R activity (IC50 = 0.53 nM) and specifically inhibited protumor M2-like macrophage survival with a minimal effect on antitumor M1-like macrophage growth. In vivo, oral administration of 12 mesylate delayed the MC38 murine colon tumor growth and reversed the immunosuppressive tumor microenvironment with the increased M1/M2

  集落刺激因子 1 受体 (CSF1R) 与肿瘤相关巨噬细胞 (TAM) 复极化有关，并已成为癌症免疫治疗的一个有前景的靶点。在此，我们描述了通过对我们的临床多靶点激酶抑制剂 BPR1K871 ( 9 ) 进行特性驱动优化来发现口服活性和选择性 CSF1R 抑制剂。分子对接揭示了独特的 7-氨基喹唑啉支架和 CSF1R 铰链区之间额外的非经典氢键 (NCHB) 相互作用，有助于 CSF1R 效力的增强。 CSF1R 和极光激酶 B (AURB) 的结构研究证明了它们后袋的差异，这启发了使用链延伸策略来减少 AURA/B 活性。先导化合物 BPR1R024 ( 12 ) 表现出强大的 CSF1R 活性 (IC 50 = 0.53 nM)，并特异性抑制促肿瘤 M2 样巨噬细胞的存活，而对抗肿瘤 M1 样巨噬细胞生长的影响最小。在体内，口服12甲磺酸盐可延缓MC38小鼠结肠肿瘤的生长，并通过增加M