新型异恶唑的合成及构效关系研究作为有效的 c-jun N-末端激酶（JNK）抑制剂。
Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors.
机构信息
Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
出版信息
Bioorg Med Chem Lett. 2014 Jan 1;24(1):161-4. doi: 10.1016/j.bmcl.2013.11.052. Epub 2013 Dec 4.
Abstract
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.
摘要
本文描述了异噁唑 3 的设计和合成，这是一种强效的 JNK 抑制剂，对 p38 的选择性是其两倍。对该支架的优化导致了化合物 27 和 28 的产生，它们通过保持化合物 3 对 JNK3 的活性，大大提高了对 p38 的选择性。我们还将描述广泛的 SAR 研究以及两种先导化合物的初步体内数据。
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