Purine analogs as phosphatidylinositol 4-kinase III beta inhibitors

Šála, Michal; Kögler, Martin; Plačková, Pavla; Mejdrová, Ivana; Hřebabecký, Hubert; Procházková, Eliška; Strunin, Dmytro; Lee, G.; Birkuš, G.; Weber, Jan; Mertlíková-Kaiserová, Helena; Nencka, Radim

doi:https://dx.doi.org/10.1016/j.bmcl.2016.04.002

Number of the records: 1

Purine analogs as phosphatidylinositol 4-kinase III beta inhibitors

1.

SYSNO ASEP	0460249
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Purine analogs as phosphatidylinositol 4-kinase III beta inhibitors
Author(s)	Šála, Michal (UOCHB-X)_{RID, ORCID} Kögler, Martin (UOCHB-X) Plačková, Pavla (UOCHB-X)_RID Mejdrová, Ivana (UOCHB-X) Hřebabecký, Hubert (UOCHB-X)_{RID, ORCID} Procházková, Eliška (UOCHB-X)_{RID, ORCID} Strunin, Dmytro (UOCHB-X) Lee, G. (US) Birkuš, G. (US) Weber, Jan (UOCHB-X)_{RID, ORCID} Mertlíková-Kaiserová, Helena (UOCHB-X)_{RID, ORCID} Nencka, Radim (UOCHB-X)_{RID, ORCID}
Source Title	Bioorganic and Medicinal Chemistry Letters. - : Elsevier - ISSN 0960-894X Roč. 26, č. 11 (2016), s. 2706-2712
Number of pages	7 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	phosphatidylinositol 4-kinase ; purine ; PI4K III beta ; antiviral agent ; hepatitis C virus
Subject RIV	CC - Organic Chemistry
R&D Projects	GA15-09310S GA ČR - Czech Science Foundation (CSF)
	LO1302 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Institutional support	UOCHB-X - RVO:61388963
UT WOS	000374988600028
EID SCOPUS	84963686126
DOI	10.1016/j.bmcl.2016.04.002
Annotation	We report on an extensive structure-activity relationship study of novel PI4K III beta inhibitors. The purine derivative of the potent screening hit T-00127-HEV1 has served as a suitable starting point for a thorough investigation of positions 8 and 2. While position 8 of the purine scaffold can only bear a small substituent to maintain the inhibitory activity, position 2 is opened for extensive modification and can accommodate even substituted phenyl rings without the loss of PI4K III beta inhibitory activity. These empirical observations nicely correlate with the results of our docking study, which suggests that position 2 directs towards solution and can provide the necessary space for the interaction with remote residues of the enzyme, whereas the cavity around position 8 is strictly limited. The obtained compounds have also been subjected to antiviral screening against a panel of (+) ssRNA viruses.
Workplace	Institute of Organic Chemistry and Biochemistry
Contact	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418
Year of Publishing	2017

Number of the records: 1