BIOMAT Database Logo BIOMAT Database Logo

Semisynthetic cephalosporins. Synthesis and structure-activity relationships of analogues with 7-acyl groups derived from 2-(cyanomethylthio)acetic acid or 2-[(2,2,2-trifluoroethyl)thio]acetic acid and their sulfoxides and sulfones. 1977

R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach

The synthesis and in vitro and in vivo activities of a series of cephalosporins having side chains derived from 2-[(2,2,2-trifluoroethyl)thio]acetic acid or 2-(cyanomethylthio)acetic acid and with acetoxymethyl or 3-heterocyclic thiomethyl substituents at the 3 position are described. In both series, increasing the oxidation state of the side-chain sulfur atom from sulfide to sulfoxide/sulfone decreased the in vitro gram-positive activity, but the effect on gram-negative activity was variable and less pronounced. The protective effectiveness in mice infected with Escherichia coli increased as the oxidation level of the side-chain sulfur was raised from sulfied to sulfoxide/sulfone. Replacement of the 3-acetoxymethyl by a 3-heterocyclic thiomethyl group resulted in overall improvement of activity both in vitro and in vivo for all oxidation states.

UI MeSH Term Description Entries
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
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002511 Cephalosporins A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. Antibiotics, Cephalosporin,Cephalosporanic Acid,Cephalosporin,Cephalosporin Antibiotic,Cephalosporanic Acids,Acid, Cephalosporanic,Acids, Cephalosporanic,Antibiotic, Cephalosporin,Cephalosporin Antibiotics
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D005463 Fluoroacetates Derivatives of acetic acid with one or more fluorines attached. They are almost odorless, difficult to detect chemically, and very stable. The acid itself, as well as the derivatives that are broken down in the body to the acid, are highly toxic substances, behaving as convulsant poisons with a delayed action. (From Miall's Dictionary of Chemistry, 5th ed)
D000085 Acetates Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure. Acetate,Acetic Acid Esters,Acetic Acids,Acids, Acetic,Esters, Acetic Acid
D000215 Acylation The addition of an organic acid radical into a molecule.
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
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

Related Publications

R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
Semisynthetic cephalosporins. Synthesis and structure-activity relationships of 7-(1-pyrryl)- and 7-(1-indolyl)acetamidocephalosporin derivatives.
September 1978, Journal of medicinal chemistry,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
Semisynthetic cephalosporins. Synthesis and structure-activity relationships of 7-sulfonylacetamido-3-cephem-4-carboxylic acids.
June 1976, Journal of medicinal chemistry,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
Semisynthetic cephalosporins. Synthesis and structure-activity relationships of 7-mandelamido-3-cephem-4-carboxylic acids.
January 1974, Journal of medicinal chemistry,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
Semisynthetic macrolide antibacterials derived from tylosin. Synthesis and structure-activity relationships of novel desmycosin analogues.
January 2004, Journal of medicinal chemistry,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
New cephalosporins with 7-acyl groups derived from beta-ketoacids. I. 7-(beta-Ketoacylamino)cephalosporins.
December 1978, The Journal of antibiotics,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
Semisynthetic cephalosporins. I. Structure-activity studies in 7-acylaminocephalosporanic acids derived from monocarboxylic acids.
January 1968, Antimicrobial agents and chemotherapy,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
Semisynthetic cephalosporins. II. Structure-activity studies in 7-acylaminocephalosporanic acids derived from dicarboxylic acids.
January 1968, Antimicrobial agents and chemotherapy,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
New cephalosporins with 7-acyl groups derived from beta-ketoacids. II. Further modifications of 7-(3-oxobutyrylamino)-cephalosporins.
December 1978, The Journal of antibiotics,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
Synthesis and structure-activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' or C-7 catechol or related aromatics.
December 1996, Bioorganic & medicinal chemistry,
R M DeMarinis, and J C Boehm, and G L Dunn, and J R Hoover, and J V Uri, and J R Guarini, and L Phillips, and P Actor, and J A Weisbach
Cephalosporins. II. Synthesis and structure-activity relationships of new 7-vinylenethioacetamido and thioacrylamido cephalosporins.
April 1981, The Journal of antibiotics,
Copied contents to your clipboard!