Structure-activity relationship of ortho- and meta-phenol based LFA-1 ICAM inhibitors |
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| Authors: | Lin Edward Yin-Shiang Guckian Kevin M Silvian Laura Chin Donovan Boriack-Sjodin P Ann van Vlijmen Herman Friedman Jessica E Scott Daniel M |
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| Affiliation: | Research and Development, Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. ted.lin@biogenidec.com |
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| 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. |
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