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L25 Medicinal Chemisty of Antihypertensives
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Questions in this quiz (10)
1The drugs that are Angiotensin II ‘blockers’ are thought to be AT1R antagonists.
- ATrue
- BFalse
2Peptides are usually very specific and have [blank_start]high[blank_end] affinity for the target, but have [blank_start]poor[blank_end] chemical and biological stability, and so a [blank_start]short[blank_end] half life. They also have [blank_start]poor[blank_end] oral bioavailability.
- Ahigh
- Blow
- Cpoor
- Dgood
- Eshort
- Flong
- Gpoor
- Hgood
3Captopril was the first orally available ACE inhibitor. It was well known to cause taste disturbances. It contains a [blank_start]proline[blank_end] amino acid, and has two S [blank_start]stereocentres[blank_end], the same stereochemistry as the endogenous peptide.
It contains a thiol because ACE is a zinc metalloenzyme, and the thiol group [blank_start]chelates[blank_end] very well to zinc. Multiple daily [blank_start]dosing[blank_end] requirements and side effects
due to thiol drove further drug discovery.- Aproline
- Bstereocentres
- Cchelates
- Ddosing
4Enalaprilat was made when the sulfhydryl part of captopril was replaced with something else that fits well into the ACE ligand [blank_start]binding[blank_end] site and can chelate to a [blank_start]zinc[blank_end] ion. Enalaprilat is 10-fold more [blank_start]potent[blank_end] than captopril.
To overcome the [blank_start]poor[blank_end] oral bioavailability of enalaprilat, the prodrug enalapril was made. Enalaprilat is converted by [blank_start]esterases[blank_end] (mostly in the liver) to enalaprilat.- Abinding
- Bzinc
- Cpotent
- Dpoor
- Eesterases
5Most other carboxylate-based ACE inhibitors (e.g Cilazapril, perindopril, quinapril) also are prodrugs that have an ester which is hydrolysed to the active drug.
- ATrue
- BFalse
6Using the endogenous ligand angiotensin as the structural starting point, angiotensin II receptor blockers were made. They are [blank_start]small molecules[blank_end] with similar key ligand-receptor contacts. They [blank_start]compete[blank_end] with angiotensin II and blocks it’s action. An example is [blank_start]losartan[blank_end].
An analogue prodrug of this is [blank_start]candesartan[blank_end] cilexetil. It is activated by [blank_start]ester[blank_end] hydrolysis which occurs during [blank_start]absorption[blank_end] from the GI tract. It is long [blank_start]acting[blank_end] –because of [blank_start]tight[blank_end] binding to AT1R and [blank_start]slow[blank_end] dissociation from the receptor.- Asmall molecules
- Bcompete
- Closartan
- Dcandesartan
- Eester
- Fabsorption
- Gacting
- Htight
- Islow
7Calcium channel blockers act at L-type [blank_start]voltage[blank_end]-gated calcium channels. L-type are [blank_start]long[blank_end]-lasting, and large, and located in skeletal, cardiac and smooth muscle. The blockers [blank_start]bind[blank_end] to the α1 subunit.
Most calcium channel blockers are dihydropyridines which have:
- [blank_start]Phenyl ring[blank_end] at C4
- [blank_start]Esters[blank_end] at C3 and C5
- [blank_start]Electron withdrawing[blank_end] group
Those funded in NZ are amlodipine, felodipine, isradipine, nifedipine, and nimodipine. All racemic except nifedapine.- Along
- Bvoltage
- Cbind
- DPhenyl ring
- EEsters
- FElectron withdrawing
8Drugs 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 [blank_start]beta[blank_end] adrenoceptors, designed via [blank_start]chain[blank_end] extension of the endogenous agonist catecholamines. The catechol is [blank_start]replaced[blank_end] with an extended structure to reduce COMT metabolism. There is a [blank_start]linker/spacer[blank_end] added between the Ar and alcohol. A short length [blank_start]bulky[blank_end] group is added to the amine. An example is propanolol.
- The 'second generation’ are [blank_start]selective[blank_end] for β1AR. All have functional groups off the phenyl ring, capable of [blank_start]hydrogen[blank_end] bonding. An example is metoprolol.
- There are also α1-AR blockers indicated for hypertension, like prazosin. They have an [blank_start]extended[blank_end] chain with an [blank_start]Ar[blank_end] group.- Abeta
- Bchain
- Creplaced
- Dlinker/spacer
- Ebulky
- Fselective
- Ghydrogen
- Hextended
- IAr
9Thiazide diuretics block the Na+Cl- symporter, disallowing Na+ reabsorption and increasing urine output. They also cause arteriolar vasodilation.
Structural requirements of the drugs:
- [blank_start]electron withdrawing[blank_end] group at C-6 (ie Cl, CF3)
- C-7 must be [blank_start]sulfonamide[blank_end]
- C-3 [blank_start]lipophilic[blank_end] group, to increase in potency and duration of action (ie benzyl)- Aelectron withdrawing
- Bsulfonamide
- Clipophilic
10Loop diuretics inhibit NKCC2 (the [blank_start]luminal[blank_end] Na/K/2Cl co-transporter) and cause a strong diuresis. They are meta-substituted sulfamoylbenzoic acids, meaning there is a [blank_start]sulfamoyl or sulfonamide[blank_end] group on one meta position of a ring and a [blank_start]benzoic[blank_end] acid on the opposite meta position.
Note: [blank_start]Bumetanide[blank_end] is more potent than [blank_start]furosemide[blank_end].- Aluminal
- Bsulfamoyl or sulfonamide
- Cbenzoic
- DBumetanide
- Efurosemide
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- User has deleted their subject information Quiz on L25 Medicinal Chemisty of Antihypertensives, created by Deleted user on 14/04/2019.
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- Created on 14 Apr 2019 · updated on 26 May 2019
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