Design, synthesis, and evaluation of novel 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective CXCR2 chemokine receptor antagonists

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5741-5. doi: 10.1016/j.bmcl.2009.08.014. Epub 2009 Aug 7.

Abstract

We describe herein a novel series of 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective inhibitors against the CXCR2 chemokine receptor and IL-8-mediated chemotaxis of a CXCR2-expressing cell line. Furthermore, these alkyl-hydrazine series inhibitors such as 5b demonstrated acceptable metabolic stability when incubated in human and rat microsomes.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • CHO Cells
  • Chemotaxis / drug effects
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Humans
  • Hydrazines / chemical synthesis*
  • Hydrazines / chemistry
  • Hydrazines / pharmacology
  • Interleukin-8 / metabolism
  • Microsomes, Liver / metabolism
  • Rats
  • Receptors, Interleukin-8B / antagonists & inhibitors*
  • Receptors, Interleukin-8B / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Hydrazines
  • Interleukin-8
  • Receptors, Interleukin-8B