Biomaterial Database

Synthesis and antibacterial activity of novel C12 vinyl ketolides. 2006

Matthew T Burger, and Xiaodong Lin, and Daniel T Chu, and Christy Hiebert, and Alice C Rico, and Mehran Seid, and Georgia L Carroll, and Lynn Barker, and Kay Huh, and Mike Langhorne, and Ribhi Shawar, and Jolene Kidney, and Kelly Young, and Scott Anderson, and Manoj C Desai, and Jacob J Plattner

Chiron Corporation, Biopharma Research, 4560 Horton Street, Emeryille, California 94608-2916, USA. matthew_burger@chiron.com

A novel series of C12 vinyl erythromycin derivatives have been discovered which exhibit in vitro and in vivo potency against key respiratory pathogens. The C12 modification involves replacing the natural C12 methyl group in the erythromycin core with a vinyl group via chemical synthesis. From the C12 vinyl macrolide core, a series of C12 vinyl ketolides was prepared. Several compounds were found to be potent against macrolide-sensitive and -resistant bacteria. The C12 vinyl ketolides 6j and 6k showed a similar antimicrobial spectrum and comparable activity to the commercial ketolide telithromycin. However, the pharmacokinetic profiles of C12 vinyl ketolides 6j and 6k in rats differ from that of telithromycin by having higher lung-to-plasma ratios, larger volumes of distribution, and longer half-lives. These pharmacokinetic differences have a pharmacodynamic effect as both 6j and 6k exhibited better in vivo efficacy than telithromycin in rat lung infection models against Streptococcus pneumoniae and Haemophilus influenzae.

UI	MeSH Term	Description	Entries
D008171	Lung Diseases	Pathological processes involving any part of the LUNG.	Pulmonary Diseases,Disease, Pulmonary,Diseases, Pulmonary,Pulmonary Disease,Disease, Lung,Diseases, Lung,Lung Disease
D008297	Male		Males
D008826	Microbial Sensitivity Tests	Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).	Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D011008	Pneumococcal Infections	Infections with bacteria of the species STREPTOCOCCUS PNEUMONIAE.	Streptococcus pneumoniae Infections,Infections, Pneumococcal,Infections, Streptococcus pneumoniae,Pneumococcal Diseases,Disease, Pneumococcal,Diseases, Pneumococcal,Infection, Pneumococcal,Infection, Streptococcus pneumoniae,Pneumococcal Disease,Pneumococcal Infection,Streptococcus pneumoniae Infection
D006192	Haemophilus Infections	Infections with bacteria of the genus HAEMOPHILUS.	Hemophilus Infections,Haemophilus influenzae Infection,Haemophilus influenzae Type b Infection,Hib Infection,Infections, Haemophilus,Infections, Hemophilus,Haemophilus Infection,Haemophilus influenzae Infections,Hemophilus Infection,Hib Infections,Infection, Haemophilus,Infection, Haemophilus influenzae,Infection, Hemophilus,Infection, Hib
D006193	Haemophilus influenzae	A species of HAEMOPHILUS found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII.	Bacterium influenzae,Coccobacillus pfeifferi,Haemophilus meningitidis,Hemophilus influenzae,Influenza-bacillus,Mycobacterium influenzae
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000900	Anti-Bacterial Agents	Substances that inhibit the growth or reproduction of BACTERIA.	Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities