title: 1,4-Diazepane-2-ones as novel inhibitors of LFA-1.
abstract: 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 IC(50) values of 110 and 70 nM, respectively.
authors.affiliation: Novartis Institute for Biomedical Research, Novartis Pharmaceuticals Corporation, 556 Morris Avenue, Summit, NJ 07901, USA. sompong.wattanasin@pharma.novartis.com
authors.forename: Sompong
authors.initials: S
authors.lastname: Wattanasin
authors.forename: Rainer
authors.initials: R
authors.lastname: Albert
authors.forename: Claus
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Didier
authors.initials: D
authors.lastname: Roche
authors.forename: Michael
authors.initials: M
authors.lastname: Sabio
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hommel
authors.forename: Karl
authors.initials: K
authors.lastname: Welzenbach
authors.forename: Gabriele
authors.initials: G
authors.lastname: Weitz-Schmidt
mesh_terms: D002474:Cell-Free System; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D015195:Drug Design; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects*; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D007202:Indicators and Reagents; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1