Combinatorial synthesis of anilinoanthraquinone derivatives and evaluation as non-nucleotide-derived P2Y2 receptor antagonists.
A library of anilinoanthraquinone derivatives was synthesized by parallel Ullmann coupling reaction of bromaminic acid with aniline derivatives in solution using a compact parallel synthesizer. The products were purified by HPLC and evaluated as antagonists at mouse and human P2Y2 receptors. 4-Phenylamino-substituted 1-amino-2-sulfoanthraquinones, for example, 1-amino-4-(2-methoxyphenyl)-2-sulfoanthraquinone (PSB-716), were potent P2Y2 antagonists with IC50 values in the low micromolar range.
Weyler
Stefanie
S
Pharmaceutical Institute, Pharmaceutical Sciences Bonn, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
Baqi
Younis
Y
Hillmann
Petra
P
Kaulich
Marko
M
Hunder
Andrea M
AM
Müller
Ingrid A
IA
Müller
Christa E
CE
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000880:Anthraquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D058919:Purinergic P2 Receptor Antagonists; D058473:Receptors, Purinergic P2Y2; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D000880:Anthraquinones; C546385:P2RY2 protein, human; C546386:P2ry2 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D058473:Receptors, Purinergic P2Y2