Influence of the C-5 substitution in polysubstituted pyrimidines on inhibition of prostaglandin E2 production.
作者： Viktor Kolman , Filip Kalčic , Petr Jansa , Zdeněk Zídek , Zlatko Janeba
DOI: 10.1016/J.EJMECH.2018.07.010
关键词: Chemistry 、 Prostaglandin E2 、 Stereochemistry 、 Potency 、 Substituent 、 Substitution (logic) 、 Cytotoxicity
摘要: Abstract As a part of broader structure-activity relationship study substituted 2-aminopyrimidines, the influence C-5 substitution on inhibition prostaglandin E2 (PGE2) production was studied. Thirty compounds were prepared starting from corresponding 2-amino-4,6-dichloropyrimidines using Suzuki cross-coupling. It shown previously that with smaller substituent (hydrogen and methyl) devoid significant activity, while 5-butyl derivatives exhibited prominent potency. In this study, other hand, both monoaryl- bisarylpyrimidines potent inhibitors PGE2 regardless length (hydrogen, methyl, n-butyl). Moreover, shorter higher potency to inhibit observed. 2-Amino-4,6-diphenylpyrimidine best inhibitor IC50 = 3 nM no cytotoxicity. The most deserve further preclinical evaluation as potential anti-inflammatory agents.
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