Structure-activity relationship study of prion inhibition by 2-aminopyridine-3,5-dicarbonitrile-based compounds: parallel synthesis, bioactivity, and in vitro pharmacokinetics.
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May BC, Zorn JA, Witkop J, Sherrill J, Wallace AC, Legname G, Prusiner SB, Cohen FE
Structure-activity relationship study of prion inhibition by 2-aminopyridine-3,5-dicarbonitrile-based compounds: parallel synthesis, bioactivity, and in vitro pharmacokinetics.
J Med Chem. 2007 Jan 11;50(1):65-73.
- PubMed ID
- 17201410 [ View in PubMed]
- Abstract
2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit prion replication in cultured cells. Here, we report findings from a comprehensive structure-activity relationship study of the 6-aminopyridine-3,5-dicarbonitrile scaffold. We identify compounds with significantly improved bioactivity (approximately 40-fold) against replication of the infectious prion isoform (PrPSc) and suitable pharmacokinetic profiles to warrant evaluation in animal models of prion disease.
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- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Piclidenoson Adenosine receptor A3 Ki (nM) 2 N/A N/A Details