吡唑并杂芳基：具有口服活性的新型p38α丝裂原活化蛋白激酶抑制骨架。
Pyrazoloheteroaryls: novel p38alpha MAP kinase inhibiting scaffolds with oral activity.
作者信息
Revesz Laszlo, Blum Ernst, Di Padova Franco E, Buhl Thomas, Feifel Roland, Gram Hermann, Hiestand Peter, Manning Ute, Neumann Ulf, Rucklin Gerard
机构信息
Novartis Institutes for BioMedical Research, Global Discovery Chemistry, CH-4002 Basel, Switzerland.
出版信息
Bioorg Med Chem Lett. 2006 Jan 15;16(2):262-6. doi: 10.1016/j.bmcl.2005.10.015. Epub 2005 Oct 24.
A test library with three novel p38alpha inhibitory scaffolds and a narrow set of substituents was prepared. Appropriate combination of substituent and scaffold generated potent p38alpha inhibitors, for example, pyrazolo[3,4-b]pyridine 9, pyrazolo[3,4-d]pyrimidine 18a and pyrazolo[3,4-b]pyrazine 23b with potent in vivo activity upon oral administration in animal models of rheumatoid arthritis.
制备了一个包含三种新型p38α抑制性骨架和一组狭窄取代基的测试库。取代基和骨架的适当组合产生了强效的p38α抑制剂，例如，吡唑并[3,4-b]吡啶9、吡唑并[3,4-d]嘧啶18a和吡唑并[3,4-b]吡嗪23b，在类风湿性关节炎动物模型中口服给药后具有强效的体内活性。
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