The team at Pharmacia subjected its most promising compounds to an exhausting pathology-toxicology evaluation. Contrary to the DuPont experience, our evaluation revealed several oxazolidinone compounds with good antibacterial activity, without toxicity problems. 1 Preclinical testing failed to demonstrate significant differences between eperezolid and linezolid, which was selected only after Phase I human clinical trials based on its superior pharmacokinetic profile. Structure-activity relationships leading to linezolid and eperezolid Unique action Faced with the task of introducing a new class of antibiotics to the marketplace, it was critical to prove that linezolid had a unique mechanism of action. This would distinguish linezolid from all other antibiotics and underscore its importance as the first member of a new class.
Antibiotics kill bacteria or prevent their growth by a variety of mechanisms.
The most common involve blocking bacterial cell wall synthesis or inhibiting bacterial protein synthesis. Early work by geneticists and biochemists demonstrated that linezolid was in fact a protein synthesis inhibitor in bacteria. Proteins are a chain of amino acids, the sequence of which determines the type and function of the protein. Continuous protein synthesis in a bacterial cell is vital for its survival. This process of single amino acid addition is termed chain elongation.