Discovery of piperidinyl aminopyrimidine derivatives as IKK-2 inhibitors

Title
Discovery of piperidinyl aminopyrimidine derivatives as IKK-2 inhibitors
Authors
김소라정진교이효선김영재김지윤최기항백두종문봉진오광석이병호신계정배애님남길수노은주조용서추현아
Keywords
IKK-2; aminopyrimidine; inhibitors; Reumatoid arthritis; Inflammation; Kinase inhibitor
Issue Date
2011-05
Publisher
Bioorganic & medicinal chemistry letters
Citation
VOL 21, NO 10, 3002-3006
Abstract
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-jB 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.
URI
http://pubs.kist.re.kr/handle/201004/40495
ISSN
0960-894X
Appears in Collections:
KIST Publication > Article
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