Synthetic Organic and Medicinal Chemistry Laboratory (SOMCL), State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China.
Bioorg Med Chem. 2011 Jul 1;19(13):3906-18. doi: 10.1016/j.bmc.2011.05.038. Epub 2011 May 24.
A series of thieno[2,3-d]pyrimidines and furo[2,3-d]pyrimidines were synthesized and evaluated for the c-Met inhibition. Thieno[2,3-d]pyrimidine 6b stood out as the most potent showing an IC(50) of 35.7 nM. This compound displayed high inhibitory effect on cell proliferation in BaF3-TPR-Met cells and showed high selectivity for c-Met family against other 14 tested kinases. However, compound 6b was found ineffective in the c-Met-dependent U-87MG human gliobastoma xenograft model that may be relevant to its poor PK profile.
一系列噻吩并[2,3-d]嘧啶和呋喃并[2,3-d]嘧啶被合成并评估了对 c-Met 的抑制作用。噻吩并[2,3-d]嘧啶 6b 表现出最强的活性，IC50 为 35.7 nM。该化合物对 BaF3-TPR-Met 细胞中的细胞增殖具有高抑制作用，并对 c-Met 家族表现出高选择性，而对其他 14 种测试的激酶则表现出低选择性。然而，化合物 6b 在 c-Met 依赖性 U-87MG 人神经胶质瘤异种移植模型中无效，这可能与其较差的 PK 特征有关。
