Synthesis and evaluation of 2-pyridinylpyrimidines as inhibitors of HIV-1 structural protein assembly

• Verfasst von: Kožíšek, Milan [VerfasserIn]
• Verfasst von: Pávová, Marcela [VerfasserIn]
• Verfasst von: Kräusslich, Hans-Georg [VerfasserIn]
• Titel: Synthesis and evaluation of 2-pyridinylpyrimidines as inhibitors of HIV-1 structural protein assembly
• Verf.angabe: Milan Kožíšek, Ondřej Štěpánek, Kamil Parkan, Carlos Berenguer Albiñana, Marcela Pávová, Jan Weber, Hans-Georg Krӓusslich, Jan Konvalinka, Aleš Machara
• E-Jahr: 2016
• Jahr: 1 August 2016
• Umfang: 4 S.
• Fussnoten: Gesehen am 28.11.2018
• Titel Quelle: Enthalten in: Bioorganic & medicinal chemistry letters
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1991
• Jahr Quelle: 2016
• Band/Heft Quelle: 26(2016), 15, Seite 3487-3490
• ISSN Quelle: 1464-3405
• DOI: doi:10.1016/j.bmcl.2016.06.039
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Assay
• Sach-SW: Assembly
• Sach-SW: Capsid
• Sach-SW: Inhibition
• Sach-SW: Pyrimidine
• K10plus-PPN: 1584592249

Abstract

In an effort to identify an HIV-1 capsid assembly inhibitor with improved solubility and potency, we synthesized two series of pyrimidine analogues based on our earlier lead compound N-(4-(ethoxycarbonyl)phenyl)-2-(pyridine-4-yl)quinazoline-4-amine. In vitro binding experiments showed that our series of 2-pyridine-4-ylpyrimidines had IC50 values higher than 28μM. Our series of 2-pyridine-3-ylpyrimidines exhibited IC50 values ranging from 3 to 60μM. The congeners with a fluoro substituent introduced at the 4-N-phenyl moiety, along with a methyl at C-6, represent potent HIV capsid assembly inhibitors binding to the C-terminal domain of the capsid protein.