title: Synthesis and biological evaluation of 2-aminothiazoles and their amide derivatives on human adenosine receptors. Lack of effect of 2-aminothiazoles as allosteric enhancers.
abstract: A number of 2-aminothiazoles (2a-e) and their amide derivatives (4-10) were prepared. The 2-aminothiazoles themselves were tested as allosteric enhancers of agonist binding to human adenosine A(1) receptors. In a variety of experimental set-ups the compounds did not show any such effect, in contrast to earlier findings by another research group. Subsequently the 2-aminothiazoles were used as intermediates in the synthesis of a number of amide derivatives of either aromatic (4-6) or aliphatic nature (7-10). Some of the compounds emerged as moderately active antagonists on human adenosine A(1) and/or A(2A) receptors with lower or negligible potency at adenosine A(3) receptors.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, PO Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Anikó
authors.initials: A
authors.lastname: Göblyös
authors.forename: Sabrina Neves
authors.initials: SN
authors.lastname: Santiago
authors.forename: Daniele
authors.initials: D
authors.lastname: Pietra
authors.forename: Thea
authors.initials: T
authors.lastname: Mulder-Krieger
authors.forename: Jacobien
authors.initials: J
authors.lastname: von Frijtag Drabbe Künzel
authors.forename: Johannes
authors.initials: J
authors.lastname: Brussee
authors.forename: Adriaan P
authors.initials: AP
authors.lastname: Ijzerman
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000577:Amides / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D015394:Molecular Structure; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000577:Amides; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D013844:Thiazoles; D005576:Colforsin; C004483:2-aminothiazole; D000242:Cyclic AMP