ethyl 4-((5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-yl)methyl)piperazine-1-carboxylate

• 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: ethyl 4-((5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-yl)methyl)piperazine-1-carboxylate
• 英文别名: Ethyl 4-[[5-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]furan-2-yl]methyl]piperazine-1-carboxylate
• 化学式: C₃₃H₃₁ClFN₅O₄
• 分子量: 616.092
• InChiKey: FPFVOXIARGRQQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  93
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 4-((5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-yl)methyl)piperazine-1-carboxylate 、 对甲苯磺酸 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 ethyl 4-((5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-yl)methyl)piperazine-1-carboxylate 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 、 sodium carbonate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 ethyl 4-((5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-yl)methyl)piperazine-1-carboxylate
  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

• 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.