MedChem I/II FS 2022 Rekonstruktion

1. cholinergic receptor
a) draw natural ligand of muscarinic & nicotinic receptor
b) What does Me do? chem. str. of methacholin & betanechol shown
c) 3 structures shown: mark pharmacophore & name 2 interactions
d) rivastigmine: how do F & Cl modify metabolism?
e) draw or explain mechanism of AChE Inhibition

2.
a) What is a Prodrug?
b) Afatinib (chem. str. shown) is a new type of T-Kinase inhibitors with a distinct mode of action. How does it work?
c) Gemeinsames Strukturelement der Kinase-Inhibitoren
d)


3.
a) nucleoside reverse transcriptase inhibitor (NRTIs): how do they work?
b) Monophosphate shown: what is the difference in mech. of action vs. NRTIs?
c)
d)


4. HIV
a) what are non-nucleoside reverse transcriptase inhibitors?
b)
c)
d)


5. b-lactam
a) 2 reasons why carboxylic acid & amine are often found in approved drugs?
b) what is a pro-drug?
c) to which class of drugs does shown structure belong to? str. of penicillin G shown
d) what's the effect of the ureido group on other shown structures (Piperacillin, a penicillin analogue)?

6.
a) what's a chemical lead? discuss binding affinity, target selectivity & PK.
b) 2 given structures, similar carbon skeleton, each with 1 different R-substituent, IC50 of 3 R possibilities: which R1 & R2 do you suggest to improve binding affinity?
c) SAR studies found out that COOH group is important for binding affinity, but reduces oral bioavailability. which of the given 3 substituents (Cl, pyrrolidin, tetrazol) would you use to substitute COOH & why?