Mer Scott
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PHCY310 Quiz on L25 Medicinal Chemisty of Antihypertensives, created by Mer Scott on 14/04/2019.

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L25 Medicinal Chemisty of Antihypertensives

Question 1 of 10

1

The drugs that are Angiotensin II ‘blockers’ are thought to be AT1R antagonists.

Select one of the following:

  • True
  • False

Explanation

Question 2 of 10

1

Select from the dropdown lists to complete the text.

Peptides are usually very specific and have ( high, low ) affinity for the target, but have ( poor, good ) chemical and biological stability, and so a ( short, long ) half life. They also have ( poor, good ) oral bioavailability.

Explanation

Question 3 of 10

1

Captopril was the first orally available ACE inhibitor. It was well known to cause taste disturbances. It contains a amino acid, and has two S , the same stereochemistry as the endogenous peptide.
It contains a thiol because ACE is a zinc metalloenzyme, and the thiol group very well to zinc. Multiple daily requirements and side effects
due to thiol drove further drug discovery.

Drag and drop to complete the text.

    proline
    stereocentres
    chelates
    dosing

Explanation

Question 4 of 10

1

Enalaprilat was made when the sulfhydryl part of captopril was replaced with something else that fits well into the ACE ligand site and can chelate to a ion. Enalaprilat is 10-fold more than captopril.
To overcome the oral bioavailability of enalaprilat, the prodrug enalapril was made. Enalaprilat is converted by (mostly in the liver) to enalaprilat.

Drag and drop to complete the text.

    binding
    zinc
    potent
    poor
    esterases

Explanation

Question 5 of 10

1

Most other carboxylate-based ACE inhibitors (e.g Cilazapril, perindopril, quinapril) also are prodrugs that have an ester which is hydrolysed to the active drug.

Select one of the following:

  • True
  • False

Explanation

Question 6 of 10

1

Using the endogenous ligand angiotensin as the structural starting point, angiotensin II receptor blockers were made. They are with similar key ligand-receptor contacts. They with angiotensin II and blocks it’s action. An example is .
An analogue prodrug of this is cilexetil. It is activated by hydrolysis which occurs during from the GI tract. It is long –because of binding to AT1R and dissociation from the receptor.

Drag and drop to complete the text.

    small molecules
    compete
    losartan
    candesartan
    ester
    absorption
    acting
    tight
    slow

Explanation

Question 7 of 10

1

Calcium channel blockers act at L-type -gated calcium channels. L-type are -lasting, and large, and located in skeletal, cardiac and smooth muscle. The blockers to the α1 subunit.
Most calcium channel blockers are dihydropyridines which have:
- at C4
- at C3 and C5
- group

Those funded in NZ are amlodipine, felodipine, isradipine, nifedipine, and nimodipine. All racemic except nifedapine.

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    long
    voltage
    bind
    Phenyl ring
    Esters
    Electron withdrawing

Explanation

Question 8 of 10

1

Drugs that block the binding of adrenalin and noradrenalin to the adrenoceptors and do not act as agonists are AR blockers.
- ‘First generation’ ARBs are non selective, acting on adrenoceptors, designed via extension of the endogenous agonist catecholamines. The catechol is with an extended structure to reduce COMT metabolism. There is a added between the Ar and alcohol. A short length group is added to the amine. An example is propanolol.
- The 'second generation’ are for β1AR. All have functional groups off the phenyl ring, capable of bonding. An example is metoprolol.
- There are also α1-AR blockers indicated for hypertension, like prazosin. They have an chain with an group.

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    beta
    chain
    replaced
    linker/spacer
    bulky
    selective
    hydrogen
    extended
    Ar

Explanation

Question 9 of 10

1

Thiazide diuretics block the Na+Cl- symporter, disallowing Na+ reabsorption and increasing urine output. They also cause arteriolar vasodilation.
Structural requirements of the drugs:
- group at C-6 (ie Cl, CF3)
- C-7 must be
- C-3 group, to increase in potency and duration of action (ie benzyl)

Drag and drop to complete the text.

    electron withdrawing
    sulfonamide
    lipophilic

Explanation

Question 10 of 10

1

Loop diuretics inhibit NKCC2 (the Na/K/2Cl co-transporter) and cause a strong diuresis. They are meta-substituted sulfamoylbenzoic acids, meaning there is a group on one meta position of a ring and a acid on the opposite meta position.
Note: is more potent than .

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    luminal
    sulfamoyl or sulfonamide
    benzoic
    Bumetanide
    furosemide

Explanation