Počet záznamů: 1

Novel (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl) methanones with restricted conformation as potent non-nucleoside reverse transcriptase inhibitors against HIV-1

SYSNO ASEP	0464300
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Novel (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl) methanones with restricted conformation as potent non-nucleoside reverse transcriptase inhibitors against HIV-1
Tvůrce(i)	Šimon, Petr (UOCHB-X)_ORCID Baszczyňski, Ondřej (UOCHB-X)_{RID, ORCID} Šaman, David (UOCHB-X)_{RID, ORCID} Stepan, G. (US) Hu, E. (US) Lansdon, E. B. (US) Jansa, P. (US) Janeba, Zlatko (UOCHB-X)_{RID, ORCID}
Zdroj.dok.	European Journal of Medicinal Chemistry. - : Elsevier - ISSN 0223-5234 Roč. 122, Oct 21 (2016), s. 185-195
Poč.str.	11 s.
Jazyk dok.	eng - angličtina
Země vyd.	FR - Francie
Klíč. slova	diarylpyrimidine (DAPY) ; etravirine ; human immunodeficiency virus (HIV) ; non-nucleoside reverse transcriptase inhibitors ; NNRTIs ; rilpivirine
Vědní obor RIV	CC - Organická chemie
Institucionální podpora	UOCHB-X - RVO:61388963
UT WOS	000383003900016
EID SCOPUS	84976503469
DOI	10.1016/j.ejmech.2016.06.026
Anotace	To elucidate the structure-geometry-activity relationship in diarylpyrimidine family (DAPYs) containing carbonyl linker between the central pyrimidine core and phenyl type B-arm, a series of (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl)methanones was designed, prepared and tested for their anti-HIV-1 activity. The carbonyl linker bearing B phenyl arm was successfully attached at both C-2 and C-4 positions of the central pyrimidine ring using a new synthetic approach. Further modifications of target compounds are present at C-5 position of the pyrimidine ring. In vitro anti-HIV-1 activity study performed on a series of 22 compounds confirmed the crucial importance of both conformational rigidity between phenyl B arm and the pyrimidine core linked through the carbonyl bridge, as well as presence of fluoro substituents in ortho-positions of phenyl B moiety. The most potent derivative of the series, compound 17, having almost perpendicular angle within the two planes made from the B aromatic arm and the pyrimidine ring, exhibited low nanomolar anti-HIV-1 activity (EC50 = 4 nM) with no significant toxicity (CC50 > 57.1 mu M).
Pracoviště	Ústav organické chemie a biochemie
Kontakt	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Rok sběru	2017

Počet záznamů: 1