17.08.21
13.20

Q: What are examples of drugs that are gained through semi-synthesis
A: Penicillin and morphin
Q: Only, morphin derivatives
A: Right, mostly natural drugs that have very complex structures where de novo synthesis is not feasible and a natural product starting molecule is used and adjusted according to demand with synthetic measures.
Q: *draw a binding pocket and drug with a hydroxy group* This hydroxy group binds through hydrogen bonding to the protein. How can you be sure that it is hydrogen bonding
A: Da hatte ich kleine Probleme habe nicht sofort die Anwort gewusst, die er wollte (Chlorid isostere, da keine H bonding eingehen kann. Habe über nur hydrogen, methoxy, amine gesprochen und erklärt was die Effekt davon auf die Bindung wären. Am Ende hat er gesagt was mit Chlorid sei und habs dann erklärt.
Q: Topic peptic ulcers what do you know?
A: receptors: histamine, acetylcholine, gastrin; proton pumps; antibiotics
Q: you mentioned histamine here are the gpcr. *shows table* what can you say from this
A: Gs und Gq und wie die Signalkaskade geht
Q: can you draw ATP and how it is converted to cAMP. what is the leaving group?
A: yup, diphosphate
Q: this is cimetidine. It was developed from the natural ligand. Why can this approach be advantageous
A: You know the starting point, and through rational design you can add groups and determine the pharmacophore and see what increase/decrease activity or acts as antagonist/agonist
Q: in cimetidine what is the function of the nitrile
A: first thiourea (toxic) -> guanidine (too basic) -> cyano group electron withdrawing (lower pka)
Q: electron withdrawing groups. What other groups could be used
A: nitro
Q: cimetidine acts on metabolic enzymes. what can you tell me about drug-drug interactions
A: certain drugs induce or inhibit the activity of metabolic enzymes which can have an impact on activity or toxicity. Specifically cytochrome p450 enz are susceptible to this
Q:*shows drug with long alkylester* this is a peculiar structure.
A: yes it has a long alkyl chain connected to an ester. This is done to reduce hydrophilicity and improve absorption in the gut. The ester is then cleaved in the blood.
Q: yes and no. the ester masks the hydroxy group and doesn’t need a long chain to reduce the hydrophilicy.
A: ahh so it is to make sure it localizes to fatty tissue like the brain or adipose tissue.
Q: the palmitate acts as a sort of sustained release where it is stored in depots and the hydrolysis is rather slow. It is an antipsychotic. The actual drug that is active is a metabolite of the administered drug. How do you imagine this drug was discovered.
A: the old approach of drug discovery as modern mthods. i.e hts would not be able to find hits for metabolites. Old approach of giving a drug and observing the effects on the organism.
Q: yup. Times up
A: :)
Q: :)