Lexicon Pharmaceuticals, Princeton, NJ 08540, United States.
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6784-7. doi: 10.1016/j.bmcl.2009.09.081. Epub 2009 Sep 25.
A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo.
一系列脱氧胞苷激酶抑制剂同时进行了效力和 PK 性质的优化。然后，一个共晶结构使该系列与高通量筛选的命中化合物融合，得到一种高活性、选择性和可口服生物利用的抑制剂，化合物 10。该化合物在体内表现出剂量依赖性的脱氧胞苷激酶抑制作用。
