Structure–activity relationship of ortho-and meta-phenol based LFA-1 ICAM inhibitors

…, PA Boriack-Sjodin, H van Vlijmen, JE Friedman…

Index: Lin, Edward Yin-Shiang; Guckian, Kevin M.; Silvian, Laura; Chin, Donovan; Ann Boriack-Sjodin; van Vlijmen, Herman; Friedman, Jessica E.; Scott, Daniel M. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 19 p. 5245 - 5248

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Citation Number: 5

Abstract

LFA-1 ICAM inhibitors based on ortho-and meta-phenol templates were designed and synthesized by Mitsunobu chemistry. The selection of targets was guided by X-ray co-crystal data, and led to compounds which showed an up to 30-fold increase in potency over reference compound 1 in the LFA-1/ICAM1-Ig assay. The most active compound exploited a new hydrogen bond to the I-domain and exhibited subnanomolar potency.