Discovery of piperidinyl aminopyrimidine derivatives as IKK-2 inhibitors
- Discovery of piperidinyl aminopyrimidine derivatives as IKK-2 inhibitors
- 김소라; 정진교; 이효선; 김영재; 김지윤; 최기항; 백두종; 문봉진; 오광석; 이병호; 신계정; 배애님; 남길수; 노은주; 조용서; 추현아
- IKK-2; aminopyrimidine; inhibitors; Reumatoid arthritis; Inflammation; Kinase inhibitor
- Issue Date
- Bioorganic & medicinal chemistry letters
- VOL 21, NO 10, 3002-3006
- 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.
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.