Identification of 4-(2-(4-amino-1, 2, 5-oxadiazol-3-yl)-1-ethyl-7-{[(3 S)-3-piperidinylmethyl] oxy}-1 H-imidazo [4, 5-c] pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a …

…, LV Lafrance, M Li, IG Safonov, DT Takata…

Index: Heerding, Dirk A.; Rhodes, Nelson; Leber, Jack D.; Clark, Tammy J.; Keenan, Richard M.; Lafrance, Louis V.; Li, Mei; Safonov, Igor G.; Takata, Dennis T.; Venslavsky, Joseph W.; Yamashita, Dennis S.; Choudhry, Anthony E.; Copeland, Robert A.; Lai, Zhihong; Schaber, Michael D.; Tummino, Peter J.; Strum, Susan L.; Wood, Edgar R.; Duckett, Derek R.; Eberwein, Derek; Knick, Victoria B.; Lansing, Timothy J.; McConnell, Randy T.; Zhang, ShuYun; Minthorn, Elisabeth A.; Concha, Nestor O.; Warren, Gregory L.; Kumar, Rakesh Journal of Medicinal Chemistry, 2008 , vol. 51, # 18 p. 5663 - 5679

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Citation Number: 88

Abstract

Overexpression of AKT has an antiapoptotic effect in many cell types, and expression of dominant negative AKT blocks the ability of a variety of growth factors to promote survival. Therefore, inhibitors of AKT kinase activity might be useful as monotherapy for the treatment of tumors with activated AKT. Herein, we describe our lead optimization studies culminating in the discovery of compound 3g (GSK690693). Compound 3g is a novel ATP competitive, ...