Discovery of piperidinyl aminopyrimidine derivatives as IKK-2 inhibitors

Sora Kim, Jin Kyo Jung, Hyo Seon Lee, Youngjae Kim, Jiyoon Kim, Kihang Choi, Du Jong Baek, Bongjin Moon, Kwang Seok Oh, Byung Ho Lee, Kye Jung Shin, Ae Nim Pae, Ghilsoo Nam, Eun Joo Roh, Yong Seo Cho, Hyunah Choo

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3002-3006
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number10
Publication statusPublished - 2011 May 15


  • Aminopyrimidine
  • IKK-2
  • Inflammation
  • Kinase inhibitor
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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