Synthesis and SAR evaluation of 1,2,4-triazoles as A2A receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 3, 2004, Pages 817-821

  Alanine, Alexander ^a   Anselm, Lilli ^a   Steward, Lucinda ^a   Thomi, Stefan ^a   Vifian, Walter ^a   Groaning, Michael D ^a,b  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b Roche Colorado   (United States)

Author keywords

1,2,4 Triazoles; A2A receptor antagonists; SAR

Indexed keywords

1,2,4 TRIAZOLE DERIVATIVE; ALPHA 2A ADRENERGIC RECEPTOR; ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; RECEPTOR BLOCKING AGENT;

ALPHA ADRENERGIC RECEPTOR BLOCKING; ARTICLE; DRUG DETERMINATION; DRUG IDENTIFICATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; IN VITRO STUDY; STRUCTURE ACTIVITY RELATION;

EID: 1642575084     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.09.095     Document Type: Article

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9. The original hit was identified as the cyclic version and was later confirmed to be the open chain form.
10. 2A) at room temperature. The assay was terminated by centrifugation (3000 rpm, 3 min) and counted in a scintillation counter (Topcount, Packard). All assays were performed in duplicate in at least two separate experiments. Graphs were plotted with the % specific binding using the iterative curve fitting program XL-fit.
11. PAMPA=Parallel Artificial Membrane Permeation Assay: Kansy M., Senner F., Gubernator K. J. Med. Chem. 41:1998;1007.
12. Solubility determined in 0.05 M phosphate buffer at pH 6.5.