Synthesis of theophylline derivatives and study of their activity as antagonists at adenosine receptors.
The synthesis of oligo(ethylene glycol)-alkene substituted theophyllines in positions 7 and/or 8 is described. The binding activity at adenosine receptors of selected derivatives was studied. Compound 2 showed high affinity for human A(2B) receptor (K(i) = 4.16 nM) with a selectivity K(iA2A)/K(iA2B) of 24.1, and a solubility in water of 1 mM. The alkenyl substituent in some of the theophylline derivatives allows for covalent attachment of them onto hydrogen-terminated silicon substrate surfaces via hydrosilylation. Alternatively, an azido group was incorporated to an oligo(ethylene glycol)theophylline derivative as an anchor for tethering the molecules on ethynyl presenting surfaces via click reaction.
Hierrezuelo
Jesús
J
Dept. de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain.
Manuel López-Romero
J
J
Dept. de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain.
Rico
Rodrigo
R
Dept. de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain.
Brea
José
J
Dept. de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Isabel Loza
M
M
Dept. de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Cai
Chengzhi
C
Department of Chemistry and Center for Materials Chemistry, University of Houston, Houston, TX 77204-5003, USA.
Algarra
Manuel
M
Centro de Geologia do Porto, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D011994:Recombinant Proteins; D013806:Theophylline