Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors.
Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors.
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新型异氧唑的合成和SAR作为有效的C-JUN N末端激酶（JNK）抑制剂。
DOI：
10.1016/j.bmcl.2013.11.052
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发表时间：
2014-01-01
影响因子：
2.7
通讯作者：
Koenig M
中科院分区：
文献类型：
--
作者：
He Y;Duckett D;Chen W;Ling YY;Cameron MD;Lin L;Ruiz CH;Lograsso PV;Kamenecka TM;Koenig M
异恶唑3的设计和合成描述，一个有效的JNK抑制剂与p38的两倍的选择性。该支架的优化导致化合物27和28，其通过保持化合物3的JNK3效力而显示出相对于p38的极大改善的选择性。将描述广泛的SAR研究以及两种先导化合物的初步体内数据。
The design and synthesis of isoxazole 3 is described, a potent JNK inhibitor with two fold selectivity over p38. Optimization of this scaffold led to compounds 27 and 28 which showed greatly improved selectivity over p38 by maintaining the JNK3 potency of compound 3. Extensive SAR studies will be described as well as preliminary in vivo data of the two lead compounds.