title: Discovery and SAR of diarylsulfide cyclopropylamide LFA-1/ICAM-1 interaction antagonists.
abstract: Diarylsulfide cyclopropylamides were synthesized and evaluated as LFA-1/ICAM-1 interaction antagonists. A substituent pattern was identified which maximized potency and minimized protein binding as exemplified by antagonist 30 (IC50 = 5 nM).
authors.affiliation: Metabolic Disease Research, Abbott Laboratories, Abbott Park, IL 60064, USA. james.link@abbott.com
authors.forename: J T
authors.initials: JT
authors.lastname: Link
authors.forename: B
authors.initials: B
authors.lastname: Sorensen
authors.forename: G
authors.initials: G
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: Pei
authors.forename: E B
authors.initials: EB
authors.lastname: Reilly
authors.forename: S
authors.initials: S
authors.lastname: Leitza
authors.forename: G
authors.initials: G
authors.lastname: Okasinski
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D020128:Inhibitory Concentration 50; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D003521:Cyclopropanes; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1