Sulfonamides drug metabolism o o h2n s o n hn s n

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: rugs Structure- AcKvity RelaKonships para- Amino group R1HN AromaKc Sulfonamide O S O NHR2 • para- Amino group is essenKal (R1=H) • para- Amido groups (R1=acyl) are allowed • inacKve in vitro, but acKve in vivo • act as prodrugs • AromaKc ring is essenKal • para- SubsKtuKon is essenKal • Sulfonamide group is essenKal • Sulfonamide nitrogen must be primary or secondary • R2 can be varied Prodrugs of sulfonamides O HN S NHR2 Me O - CH3CO2H O Enzyme O Notes • Amide group lowers the polarity of the sulfonamide • Amide cannot ionise • Alkyl group increases the hydrophobic character • Crosses the gut wall more easily • Metabolised by enzymes (e.g. pepKdases) in vivo • Metabolism generates the primary amine • Primary amine ionises and can form ionic interacKons • Ionised primary amine also acts as a strong HBD H2N S O NHR2 Sulfanilamides - applicaKons Notes • AnKbacterial drugs of choice prior to penicillins (1930s) • Superseded by penicillins Current uses • Treatment of urinary tract infecKons • Eye loKons • Treatment of gut infecKons • Treatment of mucous membrane infecKons Sulfonamide Mechanism of acKon H2N N HN H2N N H2N CO2H para-Aminobenzoic acid OP P N H N HN Dihydropteroate synthetase _ Reversible " Dihydropteroate inhibition Sulfonamides H2N H2N H CO2H CO2H N HN L-Glutamic acid N N H O H N H N Dihydrofolate O H2N N HN N H O O N O Tetrahydrofolate" (coenzyme F) H Dihydrofolate" reductase" NADPH H N N H CO2H CO2H _ Trimethoprim H N H N O H CO2H CO2H H N CO2H Sulfonamide Mechanism of acKon Target enzyme • Dihydropteroate synthetase - bacterial enzyme • Not present in human cells • Important in the biosynthesis of the tetrahydrofolate cofactor • Cofactor is crucial to pyrimidine and DNA biosynthesis • Crucial to cell growth and division Sulfonamides • CompeKKve enzyme inhibitors • Bacteriosta5c agents • Not ideal for paKents with weakened immune systems • Mimic the enzyme substr...
View Full Document

This note was uploaded on 01/15/2014 for the course CHEM 167 taught by Professor Amaro during the Winter '13 term at UCSD.

Ask a homework question - tutors are online