Abstract
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).
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Cyclophosphamide
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Drug Resistance, Multiple, Bacterial
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Escherichia coli Infections / drug therapy
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Escherichia coli Infections / etiology
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Gram-Negative Bacteria / drug effects
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Gram-Positive Bacteria / drug effects
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Male
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Methicillin Resistance
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Mice
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Microbial Sensitivity Tests
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Neutropenia / chemically induced
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Neutropenia / complications
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / chemistry
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Pyrrolidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Ribosomes / drug effects
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Ribosomes / metabolism
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Sepsis / drug therapy
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Stereoisomerism
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Structure-Activity Relationship
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Tetracycline Resistance
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Tetracyclines / chemical synthesis*
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Tetracyclines / chemistry
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Tetracyclines / pharmacology
Substances
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Anti-Bacterial Agents
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Pyrrolidines
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Tetracyclines
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eravacycline
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Cyclophosphamide