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Record Information
Version2.0
Creation Date2014-09-11 05:13:55 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4733
Identification
Common NameQuinapril
ClassSmall Molecule
DescriptionQuinapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to quinaprilat (quinapril diacid) following oral administration. Quinaprilat is a competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Quinapril may be used to treat essential hypertension and congestive heart failure.
Compound Type
  • Amide
  • Amine
  • Angiotensin-Converting Enzyme Inhibitor
  • Antihypertensive Agent
  • Drug
  • Ester
  • Ether
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Accupril
Accuprin
Accupro
Acequin
Acuitel
Korec
Quinaprilum
Quinazil
Chemical FormulaC25H30N2O5
Average Molecular Mass438.516 g/mol
Monoisotopic Mass438.215 g/mol
CAS Registry Number85441-61-8
IUPAC Name(3S)-2-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
Traditional Namequinapril
SMILES[H][C@@](C)(N[C@@]([H])(CCC1=CC=CC=C1)C(=O)OCC)C(=O)N1CC2=CC=CC=C2C[C@@]1([H])C(O)=O
InChI IdentifierInChI=1S/C25H30N2O5/c1-3-32-25(31)21(14-13-18-9-5-4-6-10-18)26-17(2)23(28)27-16-20-12-8-7-11-19(20)15-22(27)24(29)30/h4-12,17,21-22,26H,3,13-16H2,1-2H3,(H,29,30)/t17-,21-,22-/m0/s1
InChI KeyInChIKey=JSDRRTOADPPCHY-HSQYWUDLSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentDipeptides
Alternative Parents
Substituents
  • Alpha-dipeptide
  • Alpha-amino acid ester
  • N-acyl-l-alpha-amino acid
  • Alpha-amino acid amide
  • Alpha-amino acid or derivatives
  • Tetrahydroisoquinoline
  • Fatty acid ester
  • Aralkylamine
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Fatty acyl
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Amino acid or derivatives
  • Carboxamide group
  • Carboxylic acid ester
  • Amino acid
  • Secondary aliphatic amine
  • Carboxylic acid
  • Secondary amine
  • Azacycle
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Amine
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organic oxide
  • Organic nitrogen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point120-130°C
Boiling PointNot Available
Solubility1 mg/L
LogP3.2
Predicted Properties
PropertyValueSource
Water Solubility0.0085 g/LALOGPS
logP1.39ALOGPS
logP1.96ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)3.7ChemAxon
pKa (Strongest Basic)5.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area95.94 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity119.96 m³·mol⁻¹ChemAxon
Polarizability47.36 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-000i-3121900000-0dcfc70437ccde433e9dJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-014i-2419000000-dcbece099cf2c40cab65JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001r-0691700000-82303c3856cd6e62fe34JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03di-0012900000-04b3b6ea3f77b8f1dc7fJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000f-1009500000-739119c71c43d2886da1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-002g-2529200000-44c2b54cd17a4afaac8cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0032-3911000000-3b415cd9c843c9e15a8bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0000900000-183d8231af4eb3b23758JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0170-1937400000-ce19e2460a1cf7114f0fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03di-0920000000-c0d6a91687c7a7259122JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000l-0344900000-464fabf7fdbf745a44eaJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-3893000000-a8c3960669fc104c7ad3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01po-2910000000-71a6777a3ae80c108ff8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0023900000-6345f9403bef65cdcb1fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014u-0229200000-7e50a200d883930f550aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-07cu-1900000000-54d41ad46f89d62881f1JSpectraViewer
Toxicity Profile
Route of ExposurePeak plasma concentrations of quinapril occur within one hour following oral administration. The extent of absorption is at least 60%. The rate and extent of quinapril absorption are diminished moderately (approximately 25-30%) when ACCUPRIL tablets are administered during a high-fat meal.
Mechanism of ToxicityThere are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Quinaprilat, the principle active metabolite of quinapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Quinaprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.
MetabolismHepatic. Route of Elimination: Quinaprilat is eliminated primarily by renal excretion, up to 96% of an IV dose Half Life: Elimination half life is 2 hours with a prolonged terminal phase of 25 hours.
Toxicity ValuesLD50=1739mg/kg (orally in mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of hypertension and as adjunct therapy in the treatment of congestive heart failure. May also be used to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsOverdose may lead to severe hypotension. The most common adverse effects observed in controlled clinical trials were dizziness, cough, chest pain, dyspnea, fatigue, and nausea/vomiting.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00881
HMDB IDNot Available
PubChem Compound ID54892
ChEMBL IDCHEMBL1592
ChemSpider ID49565
KEGG IDC07398
UniProt IDNot Available
OMIM ID
ChEBI ID8713
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkQuinapril
References
Synthesis Reference

Om P. Goel, Uldis Krolls, “Crystalline quinapril and a process for producing the same.” U.S. Patent US4761479, issued August, 1982.

MSDST3D4733.pdf
General References
  1. Khan BV, Sola S, Lauten WB, Natarajan R, Hooper WC, Menon RG, Lerakis S, Helmy T: Quinapril, an ACE inhibitor, reduces markers of oxidative stress in the metabolic syndrome. Diabetes Care. 2004 Jul;27(7):1712-5. [15220251 ]
  2. Kieback AG, Felix SB, Reffelmann T: Quinaprilat: a review of its pharmacokinetics, pharmacodynamics, toxicological data and clinical application. Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1337-47. doi: 10.1517/17425250903282773. [19761414 ]
  3. Pitt B, O'Neill B, Feldman R, Ferrari R, Schwartz L, Mudra H, Bass T, Pepine C, Texter M, Haber H, Uprichard A, Cashin-Hemphill L, Lees RS: The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. Am J Cardiol. 2001 May 1;87(9):1058-63. [11348602 ]
  4. Tsikouris JP, Suarez JA, Meyerrose GE, Ziska M, Fike D, Smith J: Questioning a class effect: does ACE inhibitor tissue penetration influence the degree of fibrinolytic balance alteration following an acute myocardial infarction? J Clin Pharmacol. 2004 Feb;44(2):150-7. [14747423 ]
  5. Valles Prats M, Matas Serra M, Bronsoms Artero J, Mate Benito G, Torguet Escuder P, Mauri Nicolas JM: Quinapril ACE-inhibition effects on adrenergic parameters in moderate essential hypertension. Kidney Int Suppl. 1996 Jun;55:S104-6. [8743525 ]
  6. Voors AA, van Geel PP, Oosterga M, Buikema H, van Veldhuisen DJ, van Gilst WH: Vascular effects of quinapril completely depend on ACE insertion/deletion polymorphism. J Renin Angiotensin Aldosterone Syst. 2004 Sep;5(3):130-4. [15526248 ]
  7. Yamada S, Muraoka I, Kato K, Hiromi Y, Takasu R, Seno H, Kawahara H, Nabeshima T: Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis. Biol Pharm Bull. 2003 Jun;26(6):872-5. [12808303 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety.
Gene Name:
ACE
Uniprot ID:
P12821
Molecular Weight:
149713.675 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Culy CR, Jarvis B: Quinapril: a further update of its pharmacology and therapeutic use in cardiovascular disorders. Drugs. 2002;62(2):339-85. [11817979 ]
  3. Klutchko S, Blankley CJ, Fleming RW, Hinkley JM, Werner AE, Nordin I, Holmes A, Hoefle ML, Cohen DM, Essenburg AD, et al.: Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity relationships for non-sulfhydryl and sulfhydryl types. J Med Chem. 1986 Oct;29(10):1953-61. [3020249 ]
  4. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. [11929321 ]