Uses
Miransertib hydrochloride (ARQ-092 hydrochloride) is a potent, orally active, selective and allosteric Akt inhibitor with IC50s of 2.7 nM, 14 nM and 8.1 nM for Akt1, Akt2, Akt3, respectively. Miransertib hydrochloride is also a potent the AKT1-E17K mutant protein inhibitor and has the potential for PI3K/AKT-driven tumors and Proteus syndrome research[1]. Miransertib hydrochloride is effective against Leishmania[2].
Synthesis
Step 4: Tert-butyl (1 -(4-(2-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)carbamate (4.1 g) was dissolved in dichloromethane (100 mL), and a dioxane solution (20 mL) of 4.0 M HCl was slowly added. The reaction mixture was stirred at room temperature for 2.5 hours. After completion of the reaction, ether (50 mL) was added to the suspension and the solid was collected by filtration to afford 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine hydrochloride (4.032 g, white solid). The product was characterized by 1H NMR (DMSO-d6, 400 MHz) and LCMS: 1H NMR δ 8.94 (s, 3H), 8.47 (bs, 1H), 8.38 (d, J = 8.8 Hz, 1H), 8.19-8.15 (m, 1H), 8.10-8.03 (m, 3H), 7.93-7.88 (m, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.52-7.40 (m, 3H), 6.92 (t, J = 7.6 Hz, 1H), 2.70-2.57 (m, 4H), 2.29-2.20 (m, 1H), 1.90-1.80 (m, 1H); LCMS: m/z 433 [M + H]+. Calculated elemental analysis (C29H27ON7-3.06HCl-0.01C4H8O2-0.03C4H10O): C 59.61, H 5.28, N 15.36; measured values: C 59.62, H 5.05, N 15.36.
References
[1] Lapierre JM, et al. Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor. J Med Chem. 2016 Jul 14;59(13):6455-69. DOI:
10.1021/acs.jmedchem.6b00619[2] Devki Nandan, et al. Miransertib (ARQ 092), an orally-available, selective Akt inhibitor is effective against Leishmania. PLoS One. 2018 Nov 6;13(11):e0206920. DOI:
10.1371/journal.pone.0206920
![tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)carbamate](/CAS/20180601/GIF/1313881-69-4.gif)
