| Literature DB >> 15916417 |
Venkat R Macherla1, Scott S Mitchell, Rama Rao Manam, Katherine A Reed, Ta-Hsiang Chao, Benjamin Nicholson, Gordafaried Deyanat-Yazdi, Bao Mai, Paul R Jensen, William F Fenical, Saskia T C Neuteboom, Kin S Lam, Michael A Palladino, Barbara C M Potts.
Abstract
Salinosporamide A (1, NPI-0052) is a potent proteasome inhibitor in development for treating cancer. In this study, a series of analogues was assayed for cytotoxicity, proteasome inhibition, and inhibition of NF-kappaB activation. Marked reductions in potency in cell-based assays accompanied replacement of the chloroethyl group with unhalogenated substituents. Halogen exchange and cyclohexene ring epoxidation were well tolerated, while some stereochemical modifications significantly attenuated activity. These findings provide insights into structure-activity relationships within this novel series.Entities:
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Year: 2005 PMID： 15916417 DOI： 10.1021/jm048995+
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446