期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 50, 期 1, 页码 65-73出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm061045z
关键词
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资金
- NIA NIH HHS [AG02132, AG021601, AG10770] Funding Source: Medline
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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