Influence of the C-5 substitution in polysubstituted pyrimidines on inhibition of prostaglandin E2 production

0493581 - ÚOCHB 2019 RIV FR eng J - Článek v odborném periodiku
Kolman, Viktor - Kalčic, Filip - Jansa, Petr - Zídek, Zdeněk - Janeba, Zlatko
Influence of the C-5 substitution in polysubstituted pyrimidines on inhibition of prostaglandin E2 production.
European Journal of Medicinal Chemistry. Roč. 156, Aug 5 (2018), s. 295-301. ISSN 0223-5234. E-ISSN 1768-3254
Grant CEP: GA TA ČR(CZ) TE01020028
Institucionální podpora: RVO:61388963 ; RVO:68378041
Klíčová slova: pyrimidines * Suzuki-Miyaura reaction * prostaglandin E2 * inhibitor
Obor OECD: Organic chemistry; Medicinal chemistry (UEM-P)
Impakt faktor: 4.833, rok: 2018

As a part of a broader structure-activity relationship study of substituted 2-aminopyrimidines, the influence of the C-5 substitution on inhibition of prostaglandin E2 (PGE2) production was studied. Thirty compounds were prepared starting from the corresponding 2-amino-4,6-dichloropyrimidines using Suzuki cross-coupling. It was shown previously that 2-amino-4,6-dichloropyrimidines with smaller C-5 substituent (hydrogen and methyl) were devoid of significant activity, while 5-butyl derivatives exhibited prominent potency. In this study, on the other hand, both monoaryl- and bisarylpyrimidines were potent inhibitors of PGE2 production regardless the length of the C-5 substituent (hydrogen, methyl, n-butyl). Moreover, the shorter the C-5 substituent the higher potency to inhibit PGE2 production was observed. 2-Amino-4,6-diphenylpyrimidine was the best inhibitor of PGE2 production with IC50 = 3 nM and no cytotoxicity. The most potent inhibitors deserve further preclinical evaluation as potential anti-inflammatory agents.
Trvalý link: http://hdl.handle.net/11104/0286924