| Literature DB >> 11755344 |
Linda L Chang1, Quang Truong, Richard A Mumford, Linda A Egger, Usha Kidambi, Kathryn Lyons, Ermengilda McCauley, Gail Van Riper, Stella Vincent, John A Schmidt, Malcolm MacCoss, William K Hagmann.
Abstract
The alpha(4)beta(1) and alpha(4)beta(7) integrins are implicated in several inflammatory disease states. Systematic SAR studies of an alpha(4)beta(1)-specific arylsulfonyl-Pro-Tyr lead led to the identification of a new alpha(4)beta(7) binding site, best captured by O-carbamates of Tyr for this structural class. Several compounds showed a 200- to 400-fold improvement in alpha(4)beta(7) binding affinity while maintaining subnanomolar alpha(4)beta(1) activity, for example 2l, VCAM-Ig alpha(4)beta(1) IC(50)=0.13 nM, VCAM-Ig alpha(4)beta(7) IC(50)=1.92 nM.Entities:
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Year: 2002 PMID： 11755344 DOI： 10.1016/s0960-894x(01)00710-7
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823