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

Michele A Weidner-Wells; Todd C Henninger; Stephanie A Fraga-Spano; Christine M Boggs; Michele Matheis; David M Ritchie; Dennis C Argentieri; Michael P Wachter; Dennis J Hlasta

doi:10.1016/j.bmcl.2004.05.080

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

Bioorg Med Chem Lett. 2004 Aug 16;14(16):4307-11. doi: 10.1016/j.bmcl.2004.05.080.

Authors

Michele A Weidner-Wells¹, Todd C Henninger, Stephanie A Fraga-Spano, Christine M Boggs, Michele Matheis, David M Ritchie, Dennis C Argentieri, Michael P Wachter, Dennis J Hlasta

Affiliation

¹ Johnson and Johnson Pharmaceutical Research and Development, LLC 1000 Route 202, Raritan, NJ 08869, USA. mwells@prdus.jnj.com

PMID: 15261292
DOI: 10.1016/j.bmcl.2004.05.080

Abstract

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.

MeSH terms

Administration, Oral
Isoxazoles / administration & dosage
Isoxazoles / chemical synthesis
Isoxazoles / chemistry*
Isoxazoles / pharmacology*
Oxadiazoles / administration & dosage
Oxadiazoles / chemical synthesis
Oxadiazoles / chemistry*
Oxadiazoles / pharmacology*
Receptors, Interleukin-8A / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Isoxazoles
Oxadiazoles
Receptors, Interleukin-8A