Fichas
Prodrug/Sulphanomides
Fichas del conjunto (14)
- 1EXAMPLESAspirin (prodrug) --> salicylic acid (active agent)
Phenacetin (prodrug) --> paracetamol (active agent) - 2TRANSPORT CHARACTERISTICSprodrugs can interfere with transport (EXAMPLE: putting hydrophilic group may restrict gut to one specific area)
- 3PHARMACEUTICAL PROBLEMS- poor water solubility
- aesthetic properties such as taste or tissue irritation
- formulation problems - 4PHARMOKINETIC PROBLEMS- incomplete absorption of the drug across biological barriers
- too rapid absorption or excretion
- poor site specificty - 5PHARMACEUTICAL SOLUTION 1improve flavour of drug by decreasing water solubility so drug does not dissolve on the tongue (CHLORAMPHENICOL = OH --> alkyl chain)
- 6PHARMACEUTICAL SOLUTION 2reduce pain by improving water solubility. injections hurt, however when made more soluble they hurt less
(CLINDAMYCIN phosphate ester addition) - 7PHARMACEUTICAL SOLUTION 3mask drug toxicity side effects
(SALICYLIC ACID causes gastric bleeding, ASPRIN doesn't OH --> ester) - 8SULPHANOMIDE AS A PRODRUG- antibacterial agents, active drug of PRONTOSIL (prodrug)
- have a versatile synthesis with many derivates
- competes with PABA, PABA is the enzyme active in DHF synthesis - 9GENERAL SYNTHESIS
- 10SIMILARITIES WITH PABA1º aryl amine
Para substituents
Similar charges
Polar substituents
Van der Waals b/c aromatic
H-bonding
Ionic factors in substituents
Similar lengths (6.9 v. 6.7 Å)
Similar widths (2.4 v. 2.3 Å)
- 11ROLE OF DIHYDROFOLATE REDUCTASE DHF --> THF
- 12BIOSYNTHESIS OF FOLATES- DHF plays ket role in synthesis of DNA bases
- DHF introduces a methyl group into thymine
- synthesis of DHF, THF, 10-fromylTHF
-DHF not synthesised in HUMAN bodies
-DHF pathway interrupted by Trimethoprim - 13INHIBITION OF DHF PATHWAY 1- Trimethoprim and a sulphadrug are combined to hit bacteria
- high selectivity to DHF
- sulphadrug -> inhibits PABA insertion
- Trimethoprim inhibits (DHFR)
- effective for bronchial adn urinary tract infections - 14INHIBITION OF DHF PATHWAY 2- methotrexate is another inhibitor of DHF
- low selectivity for bacteria but block DHFR
- used in acute childhood leukemia, does not differentiate between normal and malignant cells
- v. toxic with serious side effects
Información
- Descripción
- Fichas sobre Prodrug/Sulphanomides, creado por Valentina Valenz el 17/05/2016.
- Creado por
- Valentina Valenz
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