N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-(piperazin-1-ylmethyl)furan-2-yl)quinazolin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-(piperazin-1-ylmethyl)furan-2-yl)quinazolin-4-amine
• 英文别名: N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-(piperazin-1-ylmethyl)furan-2-yl]quinazolin-4-amine
• 化学式: C₃₀H₂₇ClFN₅O₂
• 分子量: 544.028
• InChiKey: XVMMZTTYUZMATQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-(piperazin-1-ylmethyl)furan-2-yl)quinazolin-4-amine 在 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-((4-(methylsulfonyl)piperazin-1-yl)methyl)furan-2-yl)quinazolin-4-amine tosylate
  参考文献：
  名称：

  Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (selatinib) for the treatment of cancer

  摘要：

  To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series of new lapatinib analogs were designed and synthesized. Compared with lapatinib, L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI-N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing significant loss of body weight. And the inhibition rates of lapatinib in the two xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies revealed that the potent in vivo activities of L-2 may be mainly attributed to its superior aqueous solubility and oral bioavailability. In addition, a high-yielding one-pot procedure was developed for the synthesis of lapatinib and its analogs. (C) 2013 Elsevier Masson SAS. All tights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.032
• 作为产物：
  描述：

  4-[3-氯-4-(3-氟苄基氧)苯基氨基]-6-碘喹唑啉 在 sodium triacetoxyborohydride 、 palladium diacetate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-(piperazin-1-ylmethyl)furan-2-yl)quinazolin-4-amine
  参考文献：
  名称：

  Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (selatinib) for the treatment of cancer

  摘要：

  To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series of new lapatinib analogs were designed and synthesized. Compared with lapatinib, L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI-N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing significant loss of body weight. And the inhibition rates of lapatinib in the two xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies revealed that the potent in vivo activities of L-2 may be mainly attributed to its superior aqueous solubility and oral bioavailability. In addition, a high-yielding one-pot procedure was developed for the synthesis of lapatinib and its analogs. (C) 2013 Elsevier Masson SAS. All tights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.032

文献信息

• QUINAZOLINE DERIVATIVE, COMPOSITION HAVING THE DERIVATIVE, AND USE OF THE DERIVATIVE IN PREPARING MEDICAMENT
  申请人：Wang Shulong

  公开号：US20150080392A1

  公开（公告）日：2015-03-19

  A class of quinazoline derivatives or pharmaceutically acceptable salts or solvates thereof with novel structures is provided; meanwhile, a pharmaceutical composition comprising a pharmaceutically effective amount of said quinazoline derivatives or pharmaceutically acceptable salts or solvates thereof, and pharmaceutically acceptable excipients or additives is also provided. By modifying and transforming the quinazoline and screening of the transformed compounds on the activity of tyrosine kinase inhibition, most of the compounds have been found to possess inhibitory activity against one or several of EGFR, VEGFR-2, c-erbB-2, c-erbB-4, c-met, tie-2, PDGFR, c-src, lck, Zap70 and fyn kinases. The present invention has the advantages of reasonable design, broad source of and easy access to the raw materials, simple and easy operation of the preparation methods, mild reaction conditions, high yield of the products and being beneficial for industrial-scale production.

  提供一类具有新颖结构的喹唑啉衍生物或其药用可接受的盐或溶剂；同时，还提供了一种包含所述喹唑啉衍生物或其药用可接受的盐或溶剂的药物组合物，以及药用可接受的赋形剂或添加剂。通过修改和转化喹唑啉，并对转化后的化合物在酪氨酸激酶抑制活性上的筛选，发现大多数化合物对EGFR、VEGFR-2、c-erbB-2、c-erbB-4、c-met、tie-2、PDGFR、c-src、lck、Zap70和fyn激酶中的一个或几个具有抑制活性。本发明具有设计合理、原料来源广泛且易获得、制备方法简单易行、反应条件温和、产品产率高且有利于工业规模生产的优点。
• IMMUNOPHILIN-DEPENDENT INHIBITORS AND USES THEREOF
  申请人：The Regents of the University of California

  公开号：US20220193242A1

  公开（公告）日：2022-06-23

  Disclosed herein, inter alia, are immunophilin binding compounds and methods of using the same.
• US9499530B2
  申请人：——

  公开号：US9499530B2

  公开（公告）日：2016-11-22
• Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (selatinib) for the treatment of cancer
  作者：Long Zhang、Chuanwen Fan、Zongru Guo、Ying Li、Shuyong Zhao、Shaobo Yang、Yingying Yang、Jianrong Zhu、Dong Lin

  DOI：10.1016/j.ejmech.2013.09.032

  日期：2013.11

  To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series of new lapatinib analogs were designed and synthesized. Compared with lapatinib, L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI-N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing significant loss of body weight. And the inhibition rates of lapatinib in the two xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies revealed that the potent in vivo activities of L-2 may be mainly attributed to its superior aqueous solubility and oral bioavailability. In addition, a high-yielding one-pot procedure was developed for the synthesis of lapatinib and its analogs. (C) 2013 Elsevier Masson SAS. All tights reserved.