New 8-(trifluoromethyl)-substituted quinolones. The benefits of the 8-fluoro group with reduced phototoxic risk. 1992

J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48106.

A series of 8-(trifluoromethyl)-substituted quinolones has been prepared and evaluated for in vitro and in vivo antibacterial activity, and phototolerance in a mouse phototolerance assay. These analogues were compared to the corresponding series of 6,8-difluoro- and 6-fluoro-8H-quinolones (ciprofloxacin type). Although their in vitro antibacterial activities are less than the 6,8-difluoro analogues, the 8-(trifluoromethyl)quinolones are generally equivalent to their 8H analogues. In vivo, they are comparable to the 6,8-difluoro series and show up to 10-fold improvement in efficacy when compared to their ciprofloxacin counterparts vs Streptococcus pyogenes and Streptococcus pneumonia. In the phototolerance model, the 8-(trifluoromethyl)quinolones are comparable to the 8H-quinolones. Both of these series display much higher no effect doses (greater tolerance) than the corresponding 6,8-difluoroquinolones.

UI MeSH Term Description Entries
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
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
D010787 Photosensitivity Disorders Abnormal responses to sunlight or artificial light due to extreme reactivity of light-absorbing molecules in tissues. It refers almost exclusively to skin photosensitivity, including sunburn, reactions due to repeated prolonged exposure in the absence of photosensitizing factors, and reactions requiring photosensitizing factors such as photosensitizing agents and certain diseases. With restricted reference to skin tissue, it does not include photosensitivity of the eye to light, as in photophobia or photosensitive epilepsy. Actinic Reticuloid Syndrome,Dermatitis, Actinic,Photodermatitis,Chronic Actinic Dermatitis,Photosensitization,Actinic Dermatitides,Actinic Dermatitides, Chronic,Actinic Dermatitis,Actinic Dermatitis, Chronic,Actinic Reticuloid Syndromes,Chronic Actinic Dermatitides,Dermatitides, Actinic,Dermatitides, Chronic Actinic,Dermatitis, Chronic Actinic,Disorder, Photosensitivity,Disorders, Photosensitivity,Photodermatitides,Photosensitivity Disorder,Reticuloid Syndrome, Actinic,Reticuloid Syndromes, Actinic,Syndrome, Actinic Reticuloid,Syndromes, Actinic Reticuloid
D005260 Female Females
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
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
D000890 Anti-Infective Agents Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. Anti-Infective Agent,Anti-Microbial Agent,Antimicrobial Agent,Microbicide,Microbicides,Anti-Microbial Agents,Antiinfective Agents,Antimicrobial Agents,Agent, Anti-Infective,Agent, Anti-Microbial,Agent, Antimicrobial,Agents, Anti-Infective,Agents, Anti-Microbial,Agents, Antiinfective,Agents, Antimicrobial,Anti Infective Agent,Anti Infective Agents,Anti Microbial Agent,Anti Microbial Agents
D001424 Bacterial Infections Infections by bacteria, general or unspecified. Bacterial Disease,Bacterial Infection,Infection, Bacterial,Infections, Bacterial,Bacterial Diseases
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D042462 4-Quinolones QUINOLONES containing a 4-oxo (a carbonyl in the para position to the nitrogen). They inhibit the A subunit of DNA GYRASE and are used as antimicrobials. Second generation 4-quinolones are also substituted with a 1-piperazinyl group at the 7-position and a fluorine at the 6-position. 4-Oxoquinoline,4-Quinolinone,4-Quinolone,4-Oxoquinolines,4-Quinolinones,4 Oxoquinoline,4 Oxoquinolines,4 Quinolinone,4 Quinolinones,4 Quinolone,4 Quinolones

Related Publications

J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
April 2024, Chemistry, an Asian journal,
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
December 2002, Toxicology in vitro : an international journal published in association with BIBRA,
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
August 1991, Journal of photochemistry and photobiology. B, Biology,
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
February 2021, Chemistry (Weinheim an der Bergstrasse, Germany),
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
December 2022, Nature chemistry,
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
July 2013, European journal of clinical pharmacology,
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
January 2021, Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents,
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
January 2003, Bioorganicheskaia khimiia,
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
August 2016, Angewandte Chemie (International ed. in English),
J P Sanchez, and A J Bridges, and R Bucsh, and J M Domagala, and R D Gogliotti, and S E Hagen, and C L Heifetz, and E T Joannides, and J C Sesnie, and M A Shapiro
June 2013, Pharmaceutical research,
Copied contents to your clipboard!