tigecycline and eravacycline

This and the accompanying report (DOI: 10.1021/jm201467r ) describe the design, synthesis, and evaluation of a new generation of tetracycline antibacterial agents, 7-fluoro-9-substituted-6-demethyl-6-deoxytetracyclines ("fluorocyclines"), accessible through a recently developed total synthesis approach. These fluorocyclines possess potent antibacterial activities against multidrug resistant (MDR) Gram-positive and Gram-negative pathogens. One of the fluorocyclines, 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline (17j, also known as TP-434, 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference , Boston, MA , September 12-15, 2010 , poster F1 - 2157 ), is currently undergoing phase 2 clinical trials in patients with complicated intra-abdominal infections (cIAI).

Topics: Animals; Anti-Bacterial Agents; Cyclophosphamide; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Male; Methicillin Resistance; Mice; Microbial Sensitivity Tests; Neutropenia; Pyrrolidines; Rats; Rats, Sprague-Dawley; Ribosomes; Sepsis; Stereoisomerism; Structure-Activity Relationship; Tetracycline Resistance; Tetracyclines