| Literature DB >> 11591507 |
W K Hagmann1, P L Durette, T Lanza, N J Kevin, S E de Laszlo, I E Kopka, D Young, P A Magriotis, B Li, L S Lin, G Yang, T Kamenecka, L L Chang, J Wilson, M MacCoss, S G Mills, G Van Riper, E McCauley, L A Egger, U Kidambi, K Lyons, S Vincent, R Stearns, A Colletti, J Teffera, S Tong, J Fenyk-Melody, K Owens, D Levorse, P Kim, J A Schmidt, R A Mumford.
Abstract
Directed screening of a carboxylic acid-containing combinatorial library led to the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic characterization of this series are presented.Entities:
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Year: 2001 PMID： 11591507 DOI： 10.1016/s0960-894x(01)00544-3
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823