N-(3-phenylsulfonyl-3-piperidinoyl)-phenylalanine derivatives as potent, selective VLA-4 antagonists.


The SAR of 1-sulfonyl-cyclopentyl carboxylic acid amides, ligands for the VLA-4 integrin, was investigated. This effort resulted in the identification of N-(3-phenylsulfonyl-3-piperidinoyl)-(L)-4-(2',6'-dimethoxyphenyl)phenylalanine 52 as a potent, selective VLA-4 antagonist (IC(50)=90 pM). Expansion of the SAR demonstrated that this structural unit can be used to identify a diverse series of sub-nanomolar antagonists.

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@article{Gutteridge2003N3phenylsulfonyl3piperidinoylph, title={N-(3-phenylsulfonyl-3-piperidinoyl)-phenylalanine derivatives as potent, selective VLA-4 antagonists.}, author={Clare E. Gutteridge and Stephen E de Laszlo and Theodore M. Kamenecka and Ermengilda D McCauley and Gail van Riper and Richard A. Mumford and Usha Kidambi and Linda A Egger and Sharon X Tong and William K. Hagmann}, journal={Bioorganic & medicinal chemistry letters}, year={2003}, volume={13 5}, pages={885-90} }