Aminofurazans as potent inhibitors of AKT kinase.
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.
Rouse
Meagan B
MB
Oncology Chemistry, GlaxoSmithKline, Collegeville, PA 19426, USA.
Seefeld
Mark A
MA
Leber
Jack D
JD
McNulty
Kenneth C
KC
Sun
Lihui
L
Miller
William H
WH
Zhang
Shuyun
S
Minthorn
Elisabeth A
EA
Concha
Nestor O
NO
Choudhry
Anthony E
AE
Schaber
Michael D
MD
Heerding
Dirk A
DA
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017433:Protein Structure, Secondary / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C528328:GSK690693; D010069:Oxadiazoles; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt