title: De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.
abstract: LFA-1 (leukocyte function-associated antigen-1), is a member of the beta(2)-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases. This paper describes the de novo design, synthesis and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.
authors.affiliation: Cerep, 128, rue Danton, 92500 Rueil-Malmaison, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Potin
authors.forename: Michele
authors.initials: M
authors.lastname: Launay
authors.forename: Eric
authors.initials: E
authors.lastname: Nicolai
authors.forename: Maud
authors.initials: M
authors.lastname: Fabreguette
authors.forename: Patrice
authors.initials: P
authors.lastname: Malabre
authors.forename: François
authors.initials: F
authors.lastname: Caussade
authors.forename: Dominique
authors.initials: D
authors.lastname: Besse
authors.forename: Stacey
authors.initials: S
authors.lastname: Skala
authors.forename: Dawn K
authors.initials: DK
authors.lastname: Stetsko
authors.forename: Gordon
authors.initials: G
authors.lastname: Todderud
authors.forename: Brett R
authors.initials: BR
authors.lastname: Beno
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Cheney
authors.forename: Chiehying J
authors.initials: CJ
authors.lastname: Chang
authors.forename: Steven
authors.initials: S
authors.lastname: Sheriff
authors.forename: Diane L
authors.initials: DL
authors.lastname: Hollenbaugh
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Iwanowicz
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Suchard
authors.forename: T G Murali
authors.initials: TG
authors.lastname: Dhar
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000187:drug effects*; D008968:Molecular Conformation; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D006827:Hydantoins; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1