Moexipril

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Moexipril
Clinical data
Trade namesUnivasc
AHFS/Drugs.comMonograph
MedlinePlusa695018
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
Hepatic (active metabolite, moexiprilat)
Elimination half-life1 hour; 2-9 hours (active metabolite)
Excretion50% (faeces), 13% (urine)
Identifiers
  • (3S)-2-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H34N2O7
Molar mass498.576 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Moexipril was an

diuretics.[2]

It works by inhibiting the conversion of

angiotensin II.[3]

It was patented in 1980 and approved for medical use in 1995.[4] Moexipril is available from Schwarz Pharma under the trade name Univasc.[3][5]

Side effects

Moexipril is generally well tolerated in elderly patients with hypertension.[6] Hypotension, dizziness, increased cough, diarrhea, flu syndrome, fatigue, and flushing have been found to affect less than 6% of patients who were prescribed moexipril.[3][6]

Mechanism of action

As an ACE inhibitor, moexipril causes a decrease in ACE. This blocks the conversion of angiotensin I to angiotensin II. Blockage of angiotensin II limits hypertension within the vasculature. Additionally, moexipril has been found to possess cardioprotective properties. Rats given moexipril one week prior to induction of

fibroblasts in rats.[9]
Other ACE inhibitors have also been found to produce these actions, as well.

Pharmacology

Moexipril is available as a

ethyl ester group.[13] Moexipril is incompletely absorbed after oral administration, and its bioavailability is low.[14] The long pharmacokinetic half-life and persistent ACE inhibition of moexipril allows once-daily administration.[15]

Moexipril is highly

lipophilic,[2] and is in the same hydrophobic range as quinapril, benazepril, and ramipril.[15] Lipophilic ACE inhibitors are able to penetrate membranes more readily, thus tissue ACE may be a target in addition to plasma ACE. A significant reduction in tissue ACE (lung, myocardium, aorta, and kidney) activity has been shown after moexipril use.[8]

It has additional PDE4-inhibiting effects.[16]

Synthesis

Moexipril synthesis:[17][18]

The synthesis of the all-important dipeptide-like side chain involves alkylation of the tert-butyl ester of L-alanine (2) with ethyl 2-bromo-4-phenylbutanoate (1); the presominane of the desired isomer is attributable to asymmetric induction from the adjacent chiral center. Reaction of the product with hydrogen chloride then cleaves the tert-butyl group to give the half acid (3).[19] Coupling of that acid to the secondary amine on tetrahydroisoquinoline (4) gives the corresponding amine. The tert-butyl ester in this product is again cleaved with hydrogen chloride to afford moexipril (5).

References

  1. ISBN 978-1-4027-1740-6
    . Retrieved 2009-10-09.
  2. ^
    doi:10.4152/pea.200904463
    .
  3. ^ a b c Rodgers K, Vinson MC, Davis MW (1996). Breakthroughs: New drug approvals of 1995 -- part 1 (Report). Vol. 140. Advanstar Communications, Inc. p. 84.
  4. ISBN 9783527607495
    .
  5. ISBN 978-0-7817-2845-4
    . Retrieved 2009-10-09.
  6. ^
    PMID 8583466
    .
  7. PMID 8837552
    .
  8. ^
    PMID 9488609
    .
  9. ^
    PMID 7545893
    .
  10. PMID 1735595
    .
  11. S2CID 27296727
    .
  12. S2CID 24853463
    .
  13. PMID 17266629
    .
  14. PMID 17583172
    .
  15. ^
    PMID 11837383
    .
  16. PMID 23473803
    .
  17. Warner-Lambert
    ).
  18. PMID 3020249
    .
  19. doi:10.1080/00304948309355428
    .
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