title: Synthesis of theophylline derivatives and study of their activity as antagonists at adenosine receptors.
abstract: 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.
authors.affiliation: Dept. de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Hierrezuelo
authors.affiliation: Dept. de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Manuel López-Romero
authors.affiliation: Dept. de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Rico
authors.affiliation: Dept. de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Brea
authors.affiliation: Dept. de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Isabel Loza
authors.affiliation: Department of Chemistry and Center for Materials Chemistry, University of Houston, Houston, TX 77204-5003, USA.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Cai
authors.affiliation: Centro de Geologia do Porto, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Algarra
mesh_terms: 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*
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D011994:Recombinant Proteins; D013806:Theophylline