Proteau Antagonist Notes

Question 1

what feature of the phenol ring is important for antagonists where they cannot hydrogen bond?

Answer 1

the groups on the ring should be at the meta and para positions

Question 2

Propranolol is used as a ____

Answer 2

racemate

Question 3

the _ enantiomer of Propranolol is the active one

Answer 3

S

Question 4

Propranolol was the first _____ _ antagonist

Answer 4

general beta

Question 5

what structural differences between pronethalol and propranolol were implemented to no longer cause tumors with use of propranolol?

Answer 5

added an oxymethalene bridge

moved side chain from C2 to C1 of naphalene ring

Question 6

what makes propranolol fairly lipophilic?

Answer 6

the naphalene ring

Question 7

the ability for a beta-targeting structure to H bond likely contributes to what property of the drug?

Answer 7

gives it partial agonistic properties

Question 8

T/F an N-t-butyl group gives a drug specificity to B2 selectivity

Answer 8

False, does not specify B2 selectivity

Question 9

which enantiomer of Sotalol is active?

Answer 9

the R enantiomer

Question 10

why does Sotalol not have H bonding?

Answer 10

the methane sulfonamide group is bulky enough to prevent H bonding

Question 11

what makes Sotalol a full antagonist?

Answer 11

the methane sulfonamide group

Question 12

T/F sotalol is used as a racemate

Answer 12

true

Question 13

T/F sotalol is lipophilic

Answer 13

true

Question 14

what is the contributing structural factor for labetalols B antagonism?

Answer 14

the carboxamide group

Question 15

what likely contributes to Labetalol’s B2 partial agonism?

Answer 15

the para hydroxy group

Question 16

what agonistic/antagonistic activity do the four stereoisomers of labetalol have?

Answer 16

R,R-isomer => B1 antagonist, B2 partial agonist
R,S-isomer => inactive
S,R-isomer => a1 antagonist activity
S,S-isomer => a1 antagonist activity

Question 17

Carvedilol is given has a racemate, which enantiomer has B antagonist action? (R or S)

Answer 17

S-enantiomer

Question 18

Both enantiomers of Carvedilol have what antagonist/agonistic function?

Answer 18

both contribute to a1 antagonism

Question 19

Labetalol and Carvedilol have overall greater _ antagonism than _ antagonism

Answer 19

B

a1

Question 20

what are the three standard features of B1 antagonists that make them identifiable?

Answer 20

1. all are 4’ (para) substituted aryloxypropanolamines which lack a 3’ (meta) substituent; a small 2’ (ortho) group is possible
2. The 4’ para group is variable
3. they typically have an N-isopropyl group (never t-butyl)

Question 21

what is the major enzyme that metabolizes Metoprolol?

Answer 21

CYP2D6

Question 22

Metoprolol has which two metabolites?

are they active to CYP2D6?

Answer 22

a-hydroxy or O-demethyl metabolite

both inactive to 2D6

Question 23

T/F the SRRR isomer of nebivolol is 1000-fold more potent than the RSSS enantiomer

Answer 23

True

Question 24

d-Nebivolol is considered?

Answer 24

dextrorotatory

Question 25

l-nebivolol is considered?

Answer 25

levorotatory

Question 26

what does l-nebivolol increase?

Answer 26

nitric oxide levels causing vasodilation

Question 27

what makes Phentolamine antagonistic?

Answer 27

its large bulky group

Question 28

whats the problem with phenoxybenzamine?

Answer 28

it also alkylates serotonin and histamine receptors

Question 29

what’s unique about phenoxybenzamine in terms of it’s structure and how it effects receptors?

Answer 29

its the only antagonist that has a B-chloroethylamine substructure which is key for irreversible alkylation of the a-receptor