title: Discovery of 2,3,5-trisubstituted pyridine derivatives as potent Akt1 and Akt2 dual inhibitors.
abstract: 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.
authors.affiliation: 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
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhao
authors.forename: William H
authors.initials: WH
authors.lastname: Leister
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Robinson
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Barnett
authors.forename: Deborah
authors.initials: D
authors.lastname: Defeo-Jones
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Jones
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.forename: Joel R
authors.initials: JR
authors.lastname: Huff
authors.forename: Hans E
authors.initials: HE
authors.lastname: Huber
authors.forename: Mark E
authors.initials: ME
authors.lastname: Duggan
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
mesh_terms: 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
chemical_list: 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