Synthesis and structure-activity relationships of 3,5-diarylisoxazoles and 3,5-diaryl-1,2,4-oxadiazoles, novel classes of small molecule interleukin-8 (IL-8) receptor antagonists.
A novel series of 3,5-diarylisoxazole and 3,5-diaryl-1,2,4-oxadiazole IL-8 inhibitors has been identified. These compounds exhibit activity in an IL-8 binding assay as well as in a functional assay of IL-8 induced elastase release from neutrophils. In addition, one of the compounds exhibits oral activity in a rat adjuvant arthritis model.
Weidner-Wells
Michele A
MA
Johnson and Johnson Pharmaceutical Research and Development, LLC 1000 Route 202, Raritan, NJ 08869, USA. mwells@prdus.jnj.com
Henninger
Todd C
TC
Fraga-Spano
Stephanie A
SA
Boggs
Christine M
CM
Matheis
Michele
M
Ritchie
David M
DM
Argentieri
Dennis C
DC
Wachter
Michael P
MP
Hlasta
Dennis J
DJ
D000284:Administration, Oral; D007555:Isoxazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010069:Oxadiazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D007555:Isoxazoles; D010069:Oxadiazoles; D023062:Receptors, Interleukin-8A