1,4-Diazepane-2-ones as novel inhibitors of LFA-1

The design, synthesis, and biological evaluation of 1,4-diazepane-2-ones as novel LFA-1 antagonists from a scaffold-based combinatorial library are described. Initial optimization of the library lead has resulted in high-affinity antagonists of the LFA-1/ICAM-1 interaction, such as compounds 18d and 18e with IC50 values of 110 and 70 nM, respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.