Aminofurazans as potent inhibitors of AKT kinase

Meagan B Rouse; Mark A Seefeld; Jack D Leber; Kenneth C McNulty; Lihui Sun; William H Miller; Shuyun Zhang; Elisabeth A Minthorn; Nestor O Concha; Anthony E Choudhry; Michael D Schaber; Dirk A Heerding

doi:10.1016/j.bmcl.2009.01.002

Aminofurazans as potent inhibitors of AKT kinase

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1508-11. doi: 10.1016/j.bmcl.2009.01.002. Epub 2009 Jan 9.

Authors

Meagan B Rouse¹, Mark A Seefeld, Jack D Leber, Kenneth C McNulty, Lihui Sun, William H Miller, Shuyun Zhang, Elisabeth A Minthorn, Nestor O Concha, Anthony E Choudhry, Michael D Schaber, Dirk A Heerding

Affiliation

¹ Oncology Chemistry, GlaxoSmithKline, Collegeville, PA 19426, USA.

PMID: 19179070
DOI: 10.1016/j.bmcl.2009.01.002

Abstract

AKT inhibitors containing an imidazopyridine aminofurazan scaffold have been optimized. We have previously disclosed identification of the AKT inhibitor GSK690693, which has been evaluated in clinical trials in cancer patients. Herein we describe recent efforts focusing on investigating a distinct region of this scaffold that have afforded compounds (30 and 32) with comparable activity profiles to that of GSK690693.

Publication types

Comparative Study

MeSH terms

Animals
Cell Line
Cell Line, Tumor
Crystallography, X-Ray
Humans
Oxadiazoles / chemical synthesis*
Oxadiazoles / chemistry
Oxadiazoles / pharmacology
Oxadiazoles / therapeutic use
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology
Protein Structure, Secondary / physiology
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
Proto-Oncogene Proteins c-akt / metabolism
Structure-Activity Relationship

Substances

GSK690693
Oxadiazoles
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-akt