Xu Guozhang, Searle Lily Lee, Hughes Terry V, Beck Amanda K, Connolly Peter J, Abad Marta C, Neeper Michael P, Struble Geoffrey T, Springer Barry A, Emanuel Stuart L, Gruninger Robert H, Pandey Niranjan, Adams Mary, Moreno-Mazza Sandra, Fuentes-Pesquera Angel R, Middleton Steven A, Greenberger Lee M
Johnson & Johnson Pharmaceutical Research & Development, Medicinal Chemistry, 8 Clarke Drive, Cranbury, NJ 08512, USA.
Bioorg Med Chem Lett. 2008 Jun 15;18(12):3495-9. doi: 10.1016/j.bmcl.2008.05.024. Epub 2008 May 10.
We herein disclose a novel series of 4-aminopyrimidine-5-carbaldehyde oximes that are potent and selective inhibitors of both EGFR and ErbB-2 tyrosine kinases, with IC(50) values in the nanomolar range. Structure-activity relationship (SAR) studies elucidated a critical role for the 4-amino and C-6 arylamino moieties. The X-ray co-crystal structure of EGFR with 37 was determined and validated our design rationale.
我们在此公开了一系列新型的4-氨基嘧啶-5-甲醛肟，它们是表皮生长因子受体（EGFR）和ErbB-2酪氨酸激酶的强效且选择性抑制剂，半数抑制浓度（IC50）值在纳摩尔范围内。构效关系（SAR）研究阐明了4-氨基和C-6芳基氨基部分的关键作用。确定了EGFR与37的X射线共晶体结构，并验证了我们的设计原理。
