Discovery and SAR of diarylsulfide cyclopropylamide LFA-1/ICAM-1 interaction antagonists.
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).
Link
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JT
Metabolic Disease Research, Abbott Laboratories, Abbott Park, IL 60064, USA. james.link@abbott.com
Sorensen
B
B
Liu
G
G
Pei
Z
Z
Reilly
E B
EB
Leitza
S
S
Okasinski
G
G
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
D000577:Amides; D003521:Cyclopropanes; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1