Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6- deoxytetracycline: A potent, broad spectrum antibacterial agent

摘要

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).