Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series
Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series
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DOI：
10.1016/j.bmcl.2006.05.090
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发表时间：
2006-09-01
影响因子：
2.7
通讯作者：
Lackey, Karen E.
中科院分区：
文献类型：
--
作者：
Petrov, Kimberly G.;Zhang, Yue-Mei;Lackey, Karen E.
对6-呋喃基喹唑啉支架进行合成修饰，以优化ErbB-1/ErbB-2酪氨酸激酶的双重抑制，获得了一致的SAR，其中4-(3-氟苯氧基)-3-卤代苯胺基提供了最好的酶活性和细胞选择性。对6-呋喃基组所做的改变对酶活性几乎没有影响，但似乎显著地影响了细胞的效率。拉帕替尼的发现是从这项工作中产生的。(C)2006爱思唯尔有限公司。保留所有权利。
Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme activity, but appeared to dramatically affect the cellular efficacy. The discovery of lapatinib emerged from this work. (c) 2006 Elsevier Ltd. All rights reserved.