title: Allosteric inhibitors of Akt1 and Akt2: discovery of [1,2,4]triazolo[3,4-f][1,6]naphthyridines with potent and balanced activity.
abstract: A series of [1,2,4]triazolo[3,4-f][1,6]naphthyridine allosteric dual inhibitors of Akt1 and 2 have been developed. These compounds have been shown to have potent dual Akt1 and 2 cell potency. The representative compound 13 provided potent inhibitory activity against Akt1 and 2 in vivo in a mouse model.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., 770 Sumneytown Pike, WP14-2, West Point, PA 19486, USA. yiwei_li@merck.com
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Tony
authors.initials: T
authors.lastname: Siu
authors.forename: Essa
authors.initials: E
authors.lastname: Hu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rossi
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: Ronald G
authors.initials: RG
authors.lastname: Robinson
authors.forename: Karen
authors.initials: K
authors.lastname: Leander
authors.forename: Hans E
authors.initials: HE
authors.lastname: Huber
authors.forename: Sachin
authors.initials: S
authors.lastname: Mittal
authors.forename: Nicholas
authors.initials: N
authors.lastname: Cosford
authors.forename: Peppi
authors.initials: P
authors.lastname: Prasit
mesh_terms: D000495:Allosteric Site; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008168:Lung / Q000187:drug effects; D051379:Mice; D008956:Models, Chemical; D009287:Naphthyridines / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D009287:Naphthyridines; D014230:Triazoles; D051057:Proto-Oncogene Proteins c-akt