Anti-MRSA cephems. Part 2: C-7 cinnamic acid derivatives

Bioorg Med Chem. 2003 Jan 17;11(2):265-79. doi: 10.1016/s0968-0896(02)00336-x.

Abstract

Forty-five novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described. The compounds contain novel cinnamic acid moieties at C-7 that were synthesized using a key Heck reaction followed by nucleophilic aromatic substitution reactions. The most active compound (41) displayed an MIC(90) against MRSA of 1.0 microg/mL, and a PD(50) of 0.8 mg/kg. Compound 14 was found to be very safe in a mouse model of acute toxicity.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Cephalosporins / chemistry*
  • Cephalosporins / pharmacology*
  • Cinnamates / chemistry*
  • Cinnamates / pharmacology*
  • Disease Models, Animal
  • Lethal Dose 50
  • Methicillin Resistance
  • Mice
  • Microbial Sensitivity Tests
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / pathogenicity
  • Structure-Activity Relationship
  • Toxicity Tests, Acute

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Cinnamates