Synthesis and structure-activity relationships of new disubstituted phenyl-containing 3,4-diamino-3-cyclobutene-1,2-diones as CXCR2 receptor antagonists

Gaifa Lai; J Robert Merritt; Zhenmin He; Daming Feng; Jianhua Chao; Michael F Czarniecki; Laura L Rokosz; Tara M Stauffer; Diane Rindgen; Arthur G Taveras

doi:10.1016/j.bmcl.2008.02.010

Synthesis and structure-activity relationships of new disubstituted phenyl-containing 3,4-diamino-3-cyclobutene-1,2-diones as CXCR2 receptor antagonists

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1864-8. doi: 10.1016/j.bmcl.2008.02.010. Epub 2008 Feb 10.

Authors

Gaifa Lai¹, J Robert Merritt, Zhenmin He, Daming Feng, Jianhua Chao, Michael F Czarniecki, Laura L Rokosz, Tara M Stauffer, Diane Rindgen, Arthur G Taveras

Affiliation

¹ Pharmacopeia, Inc., 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA. galai@pcop.com

PMID: 18304809
DOI: 10.1016/j.bmcl.2008.02.010

Abstract

A series of 3,4- and 3,5-disubstituted phenyl-containing cyclobutenedione analogues were synthesized and evaluated as CXCR2 receptor antagonists. Variations in the disubstitution pattern of the phenyl ring afforded new compounds with potent CXCR2 binding affinity in the low nanomolar ranges. Moreover, two potent compounds 19 and 26 exhibited good oral pharmacokinetic profiles.

MeSH terms

Administration, Oral
Animals
Biological Availability
Cyclobutanes / chemical synthesis*
Cyclobutanes / chemistry
Cyclobutanes / pharmacology*
Haplorhini
Molecular Structure
Protein Binding
Rats
Receptors, Interleukin-8B / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Cyclobutanes
Receptors, Interleukin-8B