2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles

Hong Lin, Dennis S. Yamashita, Jin Zeng, Ren Xie, Sharad Verma, Juan I. Luengo, Nelson Rhodes, Shuyun Zhang, Kimberly A. Robell, Anthony E. Choudhry, Zhihong Lai, Rakesh Kumar, Elisabeth A. Minthorn, Kristin K. Brown, Dirk A. Heerding

Research output: Contribution to journalArticlepeer-review

Abstract

A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3β phosphorylation in a BT474 tumor xenograft model in mice.

Original languageEnglish (US)
Pages (from-to)679-683
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number2
DOIs
StatePublished - Jan 15 2010
Externally publishedYes

Keywords

  • AKT kinase inhibitors
  • Azaindazole
  • Selectivity

ASJC Scopus subject areas

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

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