开发吲哚/吲唑-氨基嘧啶作为 c-Jun N 端激酶（JNK）抑制剂：优化 JNK 效力和理化性质。
Development of indole/indazole-aminopyrimidines as inhibitors of c-Jun N-terminal kinase (JNK): optimization for JNK potency and physicochemical properties.
机构信息
Department of Medicinal Chemistry, Roche Palo Alto, Palo Alto, CA 94304, USA.
出版信息
Bioorg Med Chem Lett. 2013 Jun 15;23(12):3565-9. doi: 10.1016/j.bmcl.2013.04.029. Epub 2013 Apr 21.
A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties.
我们设计并合成了一系列新型吲哚/吲唑-氨基嘧啶类化合物，旨在使化合物对 c-Jun 激酶家族或 JNKs 具有最佳的活性和选择性。通过结构引导设计对该系列化合物进行优化，从而显著提高了化合物的活性。其中最佳化合物（17）对 JNK1 的 IC50 为 3 nM，对 JNK2 的 IC50 为 20 nM，对其他激酶的选择性大于 40 倍，具有良好的理化性质和药代动力学性质。
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