N-Isonicotinoyl-(l)-4-aminophenylalanine derivatives as tight binding VLA-4 antagonists

George A. Doherty,Ginger X. Yang,Edite Borges,Sharon Tong,Ermengilda D. McCauley,Kelly M. Treonz,Gail Van Riper,Stephen Pacholok,Qian Si,Gloria C. Koo,Kashmira Shah,Richard A. Mumford,William K. Hagmann

Bioorganic & Medicinal Chemistry Letters（2003）

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摘要

A series of isonicotinoyl-(l)-aminophenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. These compounds exhibit subnanomolar binding affinity to VLA-4 and significant off-rates. The interplay between off-rate, protein binding and pharmacokinetics is discussed.

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关键词

binding affinity,protein binding,tight binding

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