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targets (1) transporters (2)
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Identification
Name Quinapril
Accession Number DB00881 (APRD00523)
Type small molecule
Groups approved
Description

Quinapril 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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Quinapril HCl
  • Quinapril Hydrochloride
  • Quinaprilum [Latin]
Brand names
  • Accupril (Pfizer)
  • Accuprin (Pfizer (Italy))
  • Accupro (Pfizer (Austria, Denmark, Finland, Germany, Hungary, Ireland, Sweden, Switzerland, United Kingdom, Ukraine), Godecke (Czech Republic, Germany, Poland, Russia), Parke, Davis (Germany))
  • Acequin
  • Acuitel
  • Korec
  • Quinazil
Brand name mixtures
  • Accupro Comp (quinapril hydrochloride + hydrochlorothiazide)
  • Accuretic (quinapril hydrochloride + hydrochlorothiazide)
  • Accuzide (quinapril hydrochloride + hydrochlorothiazide)
  • Acequide (quinapril hydrochloride + hydrochlorothiazide)
  • Acuilix (quinapril hydrochloride + hydrochlorothiazide)
  • Bicetil (quinapril hydrochloride + hydrochlorothiazide)
  • Co-Quinapril (quinapril hydrochloride + hydrochlorothiazide)
  • Koretic (quinapril hydrochloride + hydrochlorothiazide)
  • Lidaltrin Diu (quinapril hydrochloride + hydrochlorothiazide)
  • Quimea (quinapril hydrochloride + hydrochlorothiazide)
  • QuinaLich comp (quinapril hydrochloride + hydrochlorothiazide)
  • Quinaplus (quinapril hydrochloride + hydrochlorothiazide)
  • Quinapril comp (quinapril hydrochloride + hydrochlorothiazide)
  • Quinaretic (quinapril hydrochloride + hydrochlorothiazide)
  • Quinazide (quinapril hydrochloride + hydrochlorothiazide)
  • Quiril Comp (quinapril hydrochloride + hydrochlorothiazide)
  • Stadapress (quinapril hydrochloride + hydrochlorothiazide)
Categories
  • Antihypertensive Agents
  • Angiotensin-converting Enzyme Inhibitors
CAS number 85441-61-8
Weight Average: 438.5161
Monoisotopic: 438.215472080
Chemical Formula C25H30N2O5
InChI Key InChIKey=JSDRRTOADPPCHY-HSQYWUDLSA-N
InChI
InChI=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
Plain Text
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
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2=C(C[C@H]1C(O)=O)C=CC=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Polypeptides
  • Phenylpropylamines
  • (Iso)quinolines and Derivatives
  • Amphetamines
Substructures
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Ethers
  • Benzene and Derivatives
  • Polypeptides
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Amino Acids
  • (Iso)quinolines and Derivatives
  • Amphetamines
Pharmacology
Indication For 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.
Pharmacodynamics Quinapril is a nonpeptide, non-sulfhydryl prodrug that is deesterified to quinaprilat (quinapril diacid), its major active metabolite following oral administration. Quinaprilat lowers blood pressure by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of quinaprilat by causing increased vasodilation and decreased blood pressure.
Mechanism of action There 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.
Absorption Peak 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.
Volume of distribution Not Available
Protein binding 97%
Metabolism

Hepatic.
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.
Clearance Not Available
Toxicity Overdose may lead to severe hypotension. LD50=1739mg/kg (orally in mice). The most common adverse effects observed in controlled clinical trials were dizziness, cough, chest pain, dyspnea, fatigue, and nausea/vomiting.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00153 Quinapril Pathway SMP00153
Pharmacoeconomics
Manufacturers
  • Pfizer pharmaceuticals ltd
  • Actavis totowa llc
  • Apotex inc
  • Genpharm inc
  • Invagen pharmaceuticals inc
  • Lupin ltd
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc florida
Packagers
Dosage forms
Form Route Strength
Tablet, film coated Oral 10 mg
Tablet, film coated Oral 20 mg
Tablet, film coated Oral 40 mg
Tablet, film coated Oral 5 mg
Prices
Unit description Cost Unit
Accupril 10 mg tablet 2.02 USD tablet
Accupril 20 mg tablet 2.02 USD tablet
Accupril 40 mg tablet 2.02 USD tablet
Accupril 5 mg tablet 2.02 USD tablet
Quinapril 10 mg tablet 1.57 USD tablet
Quinapril 20 mg tablet 1.57 USD tablet
Quinapril 40 mg tablet 1.57 USD tablet
Quinapril 5 mg tablet 1.57 USD tablet
Quinapril HCl 10 mg tablet 1.27 USD tablet
Quinapril HCl 20 mg tablet 1.27 USD tablet
Quinapril HCl 40 mg tablet 1.27 USD tablet
Quinapril HCl 5 mg tablet 1.27 USD tablet
Quinaretic 10-12.5 mg tablet 1.27 USD tablet
Quinaretic 20-12.5 mg tablet 1.27 USD tablet
Quinaretic 20-25 mg tablet 1.27 USD tablet
Accupril 10 mg Tablet 0.96 USD tablet
Accupril 20 mg Tablet 0.96 USD tablet
Accupril 40 mg Tablet 0.96 USD tablet
Accupril 5 mg Tablet 0.96 USD tablet
Patents
Country Patent Number Approved Expires
United States 5684016 1995-05-04 2015-05-04
Canada 2023089 2003-01-14 2010-08-10
Canada 1331615 1994-08-23 2011-08-23
Properties
State solid
Melting point 120-130oC
Experimental Properties
Property Value Source
water solubility 1 mg/L PhysProp
logP 3.2 PhysProp
Predicted Properties
Property Value Source
water solubility 8.50e-03 g/l ALOGPS
logP 1.39 ALOGPS
logP 1.94 ChemAxon Molconvert
logS -4.71 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 95.94 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 119.96 ChemAxon Molconvert
polarizability 47.36 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
External Links
Resource Link
KEGG Drug D03752 Link_out
KEGG Compound C07398 Link_out
PubChem Compound 54892 Link_out
PubChem Substance 46506309 Link_out
ChemSpider 49565 Link_out
ChEBI 8713 Link_out
ChEMBL 8713 Link_out
Therapeutic Targets Database DAP000588 Link_out
PharmGKB PA451205 Link_out
Drug Product Database 1947672 Link_out
RxList http://www.rxlist.com/cgi/generic/quinap.htm Link_out
Drugs.com http://www.drugs.com/cdi/quinapril.html Link_out
PDRhealth http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=Acc1002.html&contentName=Accupril&contentId=03 Link_out
Wikipedia http://en.wikipedia.org/wiki/Quinapril Link_out
ATC Codes
  • C09AA06
AHFS Codes
  • 24:32.04
PDB Entries
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Do not take with a high-fat meal.
  • Herbs that may attenuate the antihypertensive effect of quinapril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of quinapril.
  • Quinapril may decrease the excretion of potassium. Salt substitutes containing potassium may increase the risk of hyperkalemia.
Targets

1. Angiotensin-converting enzyme

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P12821 Link_out
Gene: ACE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Culy CR, Jarvis B: Quinapril: a further update of its pharmacology and therapeutic use in cardiovascular disorders. Drugs. 2002;62(2):339-85. Pubmed
  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. Pubmed
  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. Pubmed
Transporters

1. Oligopeptide transporter, small intestine isoform

Actions: substrate

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products

UniProt ID: P46059 Link_out
Gene: SLC15A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. Epub 2008 Aug 19. Pubmed

2. Oligopeptide transporter, kidney isoform

Actions: substrate

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides

UniProt ID: Q16348 Link_out
Gene: SLC15A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. Epub 2008 Aug 19. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:43

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.