کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361946 981475 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of piperidinyl aminopyrimidine derivatives as IKK-2 inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery of piperidinyl aminopyrimidine derivatives as IKK-2 inhibitors
چکیده انگلیسی

A serine–threonine kinase IKK-2 plays an important role in activation of NF-κB through phosphorylation of the inhibitor of NF-κB (IκB). As NF-κB is a major transcription factor that regulates genes responsible for cell proliferation and inflammation, development of selective IKK-2 inhibitors has been an important area of anti-inflammatory and anti-cancer research. In this study, to obtain active and selective IKK-2 inhibitors, various substituents were introduced to a piperidinyl aminopyrimidine core structure. The structure–activity relationship study indicated that hydrogen, methanesulfonyl, and aminosulfonyl groups substituted at the piperidinylamino functionality provide high inhibitory activity against IKK-2. Also, morpholinosulfonyl and piperazinosulfonyl group substituted at the aromatic ring attached to the aminopyrimidine core significantly increased the inhibitory activity of the resulting derivatives. In particular, compound 17 with the aromatic piperazinosulfonyl substituent showed the most potent (IC50 = 1.30 μM) and selective (over other kinases such as p38α, p38β, JNK1, JNK2, JNK3, and IKK-1) inhibitory activity against IKK-2.

Piperidinyl aminopyrimidine derivatives as IKK-2 inhibitors were synthesized and their biological results were reported.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 10, 15 May 2011, Pages 3002–3006
نویسندگان
, , , , , , , , , , , , , , , ,