Discovery of 2,3,5-trisubstituted pyridine derivatives as potent Akt1 and Akt2 dual inhibitors.
This letter describes the discovery of a novel series of dual Akt1/Akt2 kinase inhibitors, based on a 2,3,5-trisubstituted pyridine scaffold. Compounds from this series, which contain a 5-tetrazolyl moiety, exhibit more potent inhibition of Akt2 than Akt1.
Zhao
Zhijian
Z
Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck Research Laboratories, Merck & Co., PO Box 4, West Point, PA 19486, USA. zhijian_zhao@merck.com
Leister
William H
WH
Robinson
Ronald G
RG
Barnett
Stanley F
SF
Defeo-Jones
Deborah
D
Jones
Raymond E
RE
Hartman
George D
GD
Huff
Joel R
JR
Huber
Hans E
HE
Duggan
Mark E
ME
Lindsley
Craig W
CW
D000818:Animals; D002463:Cell Membrane Permeability; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D011725:Pyridines; C494918:AKT1 protein, human; C494921:AKT2 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt