Identification

Name
Trandolapril
Accession Number
DB00519  (APRD01269)
Type
Small Molecule
Groups
Approved
Description

Trandolapril is a non-sulhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to its biologically active diacid form, trandolaprilat, in the liver. Trandolaprilat inhibits 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). Trandolapril may be used to treat mild to moderate hypertension, to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction, as an adjunct treatment for congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.

Structure
Thumb
Synonyms
  • Trandolapril
  • Trandolaprilum
External IDs
RU 44570 / RU-44570
Product Ingredients
IngredientUNIICASInChI Key
Trandolapril hydrochloride3EY8XK2J4T87725-72-2QNSWMJYOGMUVGO-REWXTUPXSA-N
Active Moieties
NameKindUNIICASInChI Key
TrandolaprilatprodrugRR6866VL0O87679-71-8AHYHTSYNOHNUSH-HXFGRODQSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MavikTablet2 mg/1OralAbbvie1996-04-262017-07-31Us
MavikCapsule4 mgOralBgp Pharma Ulc2003-11-01Not applicableCanada
MavikCapsule1 mgOralBgp Pharma Ulc1998-01-07Not applicableCanada
MavikTablet4 mg/1OralPhysicians Total Care, Inc.2004-06-25Not applicableUs
MavikTablet4 mg/1OralAbbvie1996-04-262016-04-30Us
MavikCapsule0.5 mgOralBgp Pharma Ulc1998-01-28Not applicableCanada
MavikCapsule2 mgOralBgp Pharma Ulc1998-01-14Not applicableCanada
MavikTablet1 mg/1OralAbbvie1996-04-262017-06-30Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mylan-trandolaprilCapsule0.5 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada
Mylan-trandolaprilCapsule2 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada
Mylan-trandolaprilCapsule1 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada
Mylan-trandolaprilCapsule4 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada
TrandolaprilTablet4 mg/1OralGlenmark Generics, Inc. USA2008-06-182009-11-03Us
TrandolaprilTablet2 mg/1OralMed Pharma Co., Ltd.2007-06-122012-08-01Us
TrandolaprilTablet2 mg/1OralRising Health, Llc2007-06-12Not applicableUs
TrandolaprilTablet1 mg/1OralCore Pharma, Llc2007-06-132012-03-31Us
TrandolaprilTablet4 mg/1OralAurobindo Pharma2007-06-12Not applicableUs
TrandolaprilTablet2 mg/1OralActavis Pharma Company2007-06-122019-02-28Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
TarkaTrandolapril (4 mg/1) + Verapamil hydrochloride (240 mg/1)Tablet, film coated, extended releaseOralPhysicians Total Care, Inc.2009-06-25Not applicableUs00074 3290 13 nlmimage10 ec1d766b
TarkaTrandolapril (4 mg) + Verapamil hydrochloride (240 mg)Tablet, extended releaseOralBgp Pharma Ulc2002-07-15Not applicableCanada
TarkaTrandolapril (4 mg/1) + Verapamil hydrochloride (240 mg/1)Tablet, film coated, extended releaseOralAbbVie Inc.1996-10-22Not applicableUs0074 329020180814 13942 gpsp61
TarkaTrandolapril (1 mg) + Verapamil hydrochloride (240 mg)Tablet, extended releaseOralAbbott2002-07-152010-11-12Canada
TarkaTrandolapril (1 mg/1) + Verapamil hydrochloride (240 mg/1)Tablet, film coated, extended releaseOralAbbVie Inc.1996-10-222018-02-28Us
TarkaTrandolapril (2 mg/1) + Verapamil hydrochloride (180 mg/1)Tablet, film coated, extended releaseOralPhysicians Total Care, Inc.2009-01-01Not applicableUs
TarkaTrandolapril (2 mg) + Verapamil hydrochloride (180 mg)Tablet, extended releaseOralAbbott2002-07-152010-11-12Canada
TarkaTrandolapril (2 mg/1) + Verapamil hydrochloride (180 mg/1)Tablet, film coated, extended releaseOralAbbVie Inc.1996-10-22Not applicableUs
TarkaTrandolapril (2 mg) + Verapamil hydrochloride (240 mg)Tablet, extended releaseOralBgp Pharma Ulc2002-07-15Not applicableCanada
TarkaTrandolapril (2 mg/1) + Verapamil hydrochloride (240 mg/1)Tablet, film coated, extended releaseOralAbbVie Inc.1996-10-22Not applicableUs
International/Other Brands
Mavik
Categories
UNII
1T0N3G9CRC
CAS number
87679-37-6
Weight
Average: 430.5372
Monoisotopic: 430.246772208
Chemical Formula
C24H34N2O5
InChI Key
VXFJYXUZANRPDJ-WTNASJBWSA-N
InChI
InChI=1S/C24H34N2O5/c1-3-31-24(30)19(14-13-17-9-5-4-6-10-17)25-16(2)22(27)26-20-12-8-7-11-18(20)15-21(26)23(28)29/h4-6,9-10,16,18-21,25H,3,7-8,11-15H2,1-2H3,(H,28,29)/t16-,18+,19-,20-,21-/m0/s1
IUPAC Name
(2S,3aR,7aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydro-1H-indole-2-carboxylic acid
SMILES
[H][C@@]12C[C@H](N(C(=O)[C@H](C)N[C@@H](CCC3=CC=CC=C3)C(=O)OCC)[C@@]1([H])CCCC2)C(O)=O

Pharmacology

Indication

For the treatment of mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure (CHF), to improve survival following myocardial infarction (MI) in individuals who are hemodynamically stable and demonstrate symptoms of left ventricular systolic dysfunction or signs of CHF within a few days following acute MI, and to slow progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.

Associated Conditions
Pharmacodynamics

Trandolapril is the ethyl ester prodrug of a nonsulfhydryl ACE inhibitor, trandolaprilat. Trandolapril is deesterified in the liver to the diacid metabolite, trandolaprilat, which is approximately eight times more active as an inhibitor of ACE than its parent compound. ACE is a peptidyl dipeptidase that is part 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 via 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 further sustain the effects of trandolaprilat by causing increased vasodilation and decreased blood pressure. The blood pressure lowering effect of trandolaprilat is due to a decrease in peripheral vascular resistance, which is not accompanied by significant changes in urinary excretion of chloride or potassium or water or sodium retention.

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. Trandolaprilat, the active metabolite of trandolapril, 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. Trandolaprilat 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.

TargetActionsOrganism
AAngiotensin-converting enzyme
inhibitor
Human
Absorption

~ 40-60% absorbed; extensive first pass metabolism results in a low bioavailability of 4-14%

Volume of distribution
  • 18 L
Protein binding

Serum protein binding of trandolapril is ~ 80% (independent of concentration and not saturable) while that of trandolaprilat is 65 to 94% (concentration-dependent and saturable).

Metabolism

Cleavage of the ester group of trandolapril, primarily in the liver, is responsible for conversion to trandolaprilat, the active metabolite. Seven other metabolites, including diketopiperazine and glucuronide conjugated derivatives of trandolapril and trandolaprilat, have been identified.

Route of elimination

After oral administration of trandolapril, about 33% of parent drug and metabolites are recovered in urine, mostly as trandolaprilat, with about 66% in feces.

Half life

The elimination half lives of trandolapril and trandolaprilat are about 6 and 10 hours, respectively, but, similar to all ACE inhibitors, trandolaprilat also has a prolonged terminal elimination phase that involves a small fraction of administered drug. This likely represents drug binding to plasma and tissue ACE. The effective half life of elimination for trandolaprilat is 16-24 hours.

Clearance
  • 52 L/h [After approximately 2 mg IV doses]
Toxicity

Most likely clinical manifestations of overdose are symptoms of severe hypotension. Most common adverse effects include cough, headache and dizziness. The oral LD50 of trandolapril in mice was 4875 mg/kg in males and 3990 mg/kg in females. In rats, an oral dose of 5000 mg/kg caused low mortality (1 male out of 5; 0 females). In dogs, an oral dose of 1000 mg/kg did not cause mortality and abnormal clinical signs were not observed.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Trandolapril Action PathwayDrug action
Trandolapril Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidTrandolapril may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Trandolapril is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of hypertension can be increased when Trandolapril is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of hypertension can be increased when Trandolapril is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of hypertension can be increased when Trandolapril is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of hypertension can be increased when Trandolapril is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of hypertension can be increased when Trandolapril is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of hypertension can be increased when Trandolapril is combined with 5-methoxy-N,N-dimethyltryptamine.
AbediterolThe risk or severity of hypertension can be increased when Trandolapril is combined with Abediterol.
AcebutololThe risk or severity of adverse effects can be increased when Trandolapril is combined with Acebutolol.
Food Interactions
  • Herbs that may attenuate the antihypertensive effect of trandolapril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of trandolapril.
  • Take without regard to meals.
  • Trandolapril may decrease the excretion of potassium. Salt substitutes containing potassium may increase the risk of hyperkalemia.

References

Synthesis Reference

Narendra Joshi, Shekhar Bhirud, Buddhavarapu Ramam, Arjun Bodkhe, "Process for the preparation of intermediates of trandolapril and use thereof for the preparation of trandolapril." U.S. Patent US20060079698, issued April 13, 2006.

US20060079698
General References
  1. Berl T: Review: renal protection by inhibition of the renin-angiotensin-aldosterone system. J Renin Angiotensin Aldosterone Syst. 2009 Mar;10(1):1-8. doi: 10.1177/1470320309102747. [PubMed:19286752]
  2. Conen H, Brunner HR: Pharmacologic profile of trandolapril, a new angiotensin-converting enzyme inhibitor. Am Heart J. 1993 May;125(5 Pt 2):1525-31. [PubMed:8480624]
  3. Diaz A, Ducharme A: Update on the use of trandolapril in the management of cardiovascular disorders. Vasc Health Risk Manag. 2008;4(6):1147-58. [PubMed:19337528]
  4. Guay DR: Trandolapril: a newer angiotensin-converting enzyme inhibitor. Clin Ther. 2003 Mar;25(3):713-75. [PubMed:12852701]
  5. Jouquey S, Stepniewski JP, Hamon G: Trandolapril dose-response in spontaneously hypertensive rats: effects on ACE activity, blood pressure, and cardiac hypertrophy. J Cardiovasc Pharmacol. 1994;23 Suppl 4:S16-8. [PubMed:7527096]
  6. Reynolds NA, Wagstaff AJ, Keam SJ: Trandolapril/verapamil sustained release: a review of its use in the treatment of essential hypertension. Drugs. 2005;65(13):1893-914. [PubMed:16114984]
  7. Rubio-Guerra AF, Vargas-Robles H, Vargas-Ayala G, Rodriguez-Lopez L, Escalante-Acosta BA: The effect of trandolapril and its fixed-dose combination with verapamil on circulating adhesion molecules levels in hypertensive patients with type 2 diabetes. Clin Exp Hypertens. 2008 Oct;30(7):682-8. doi: 10.1080/10641960802251941. [PubMed:18855271]
  8. Sanbe A, Tanonaka K, Kobayasi R, Takeo S: Effects of long-term therapy with ACE inhibitors, captopril, enalapril and trandolapril, on myocardial energy metabolism in rats with heart failure following myocardial infarction. J Mol Cell Cardiol. 1995 Oct;27(10):2209-22. [PubMed:8576937]
  9. Torp-Pedersen C, Kober L: Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation. Lancet. 1999 Jul 3;354(9172):9-12. [PubMed:10406358]
  10. Authors unspecified: Trandolapril: an ACE inhibitor for treatment of hypertension. Med Lett Drugs Ther. 1996 Nov 22;38(988):104-5. [PubMed:8941256]
  11. Wiseman LR, McTavish D: Trandolapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in essential hypertension. Drugs. 1994 Jul;48(1):71-90. [PubMed:7525196]
  12. Zannad F: Trandolapril. How does it differ from other angiotensin converting enzyme inhibitors? Drugs. 1993;46 Suppl 2:172-81; discussion 182. [PubMed:7512472]
External Links
Human Metabolome Database
HMDB0014660
KEGG Drug
D00383
PubChem Compound
5484727
PubChem Substance
46508300
ChemSpider
4588590
BindingDB
50369775
ChEBI
9649
ChEMBL
CHEMBL1519
Therapeutic Targets Database
DAP000583
PharmGKB
PA451737
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Trandolapril
ATC Codes
C09AA10 — TrandolaprilC09BB10 — Trandolapril and verapamil
AHFS Codes
  • 24:32.04 — Angiotensin-converting Enzyme Inhibitors
MSDS
Download (57.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
1CompletedTreatmentHealthy Volunteers2
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Disorders1
3CompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
4CompletedTreatmentCoronary Artery Disease / High Blood Pressure (Hypertension)1
4CompletedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4CompletedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension) / Proteinuria1
4CompletedTreatmentHeart Failure, Unspecified / Ventricular Dysfunction, Left1
4CompletedTreatmentHigh Blood Pressure (Hypertension)3
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Induction of intra-operative hypotension1
4Unknown StatusTreatmentAortic Valve Stenosis1

Pharmacoeconomics

Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Aurobindo pharma ltd
  • Cipla ltd
  • Corepharma llc
  • Dr reddys laboratories ltd
  • Epic pharma llc
  • Invagen pharmaceuticals inc
  • Lupin ltd
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
Packagers
  • Abbott Laboratories Ltd.
  • Arrow Pharm Malta Ltd.
  • Aurobindo Pharma Ltd.
  • BASF Corp.
  • Cipla Ltd.
  • Cobalt Pharmaceuticals Inc.
  • Corepharma LLC
  • DAVA Pharmaceuticals
  • Doctor Reddys Laboratories Ltd.
  • Glenmark Generics Ltd.
  • Greenstone LLC
  • InvaGen Pharmaceuticals Inc.
  • Lupin Pharmaceuticals Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
  • Sandoz
  • Teva Pharmaceutical Industries Ltd.
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral0.5 mg
CapsuleOral1 mg
CapsuleOral2 mg
CapsuleOral4 mg
Tablet, extended releaseOral
Tablet, film coated, extended releaseOral
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral4 mg/1
Prices
Unit descriptionCostUnit
Tarka 1-240 mg Controlled Release Tabs3.46USD tab
Tarka 4-240 mg Controlled Release Tabs3.4USD tab
Tarka 1-240 mg tablet sa3.33USD tablet
Tarka 2-180 mg tablet sa3.33USD tablet
Tarka 2-240 mg Controlled Release Tabs3.33USD tab
Tarka 2-240 mg tablet sa3.33USD tablet
Tarka 4-240 mg tablet sa3.33USD tablet
Tarka 2-180 mg Controlled Release Tabs3.29USD tab
Mavik 2 mg tablet1.61USD tablet
Mavik 4 mg tablet1.61USD tablet
Mavik 1 mg tablet1.47USD tablet
Trandolapril 1 mg tablet1.24USD tablet
Trandolapril 2 mg tablet1.23USD tablet
Trandolapril 4 mg tablet1.23USD tablet
Mavik 4 mg Capsule1.03USD capsule
Mavik 2 mg Capsule0.83USD capsule
Mavik 1 mg Capsule0.72USD capsule
Mavik 0.5 mg Capsule0.42USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5744496No1998-04-282015-04-28Us
CA2023089No2003-01-142010-08-10Canada
CA1341206No2001-03-202018-03-20Canada

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)119-123 °CNot Available
logP3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0207 mg/mLALOGPS
logP1.31ALOGPS
logP1.95ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)3.8ChemAxon
pKa (Strongest Basic)5.21ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area95.94 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity115.79 m3·mol-1ChemAxon
Polarizability46.79 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9303
Blood Brain Barrier-0.8908
Caco-2 permeable-0.8501
P-glycoprotein substrateSubstrate0.7744
P-glycoprotein inhibitor IInhibitor0.5527
P-glycoprotein inhibitor IIInhibitor0.7759
Renal organic cation transporterNon-inhibitor0.8336
CYP450 2C9 substrateNon-substrate0.8227
CYP450 2D6 substrateNon-substrate0.8935
CYP450 3A4 substrateSubstrate0.5515
CYP450 1A2 substrateNon-inhibitor0.915
CYP450 2C9 inhibitorNon-inhibitor0.785
CYP450 2D6 inhibitorNon-inhibitor0.9018
CYP450 2C19 inhibitorNon-inhibitor0.796
CYP450 3A4 inhibitorNon-inhibitor0.5339
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6906
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9188
BiodegradationNot ready biodegradable0.9587
Rat acute toxicity2.2048 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9811
hERG inhibition (predictor II)Non-inhibitor0.5531
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound 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.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Alpha amino acid esters / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Indoles and derivatives / Pyrrolidine carboxylic acids / N-acylpyrrolidines / Aralkylamines / Fatty acid esters / Benzene and substituted derivatives / Dicarboxylic acids and derivatives
show 10 more
Substituents
Alpha-dipeptide / Alpha-amino acid ester / N-acyl-l-alpha-amino acid / N-acyl-alpha-amino acid / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Alpha-amino acid or derivatives / Indole or derivatives / N-acylpyrrolidine / Pyrrolidine carboxylic acid
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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...
Gene Name
ACE
Uniprot ID
P12821
Uniprot Name
Angiotensin-converting enzyme
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. [PubMed:11752352]
  2. Piepho RW: Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1;57 Suppl 1:S3-7. [PubMed:11030016]
  3. 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:11929321]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Zhu HJ, Appel DI, Johnson JA, Chavin KD, Markowitz JS: Role of carboxylesterase 1 and impact of natural genetic variants on the hydrolysis of trandolapril. Biochem Pharmacol. 2009 Apr 1;77(7):1266-72. doi: 10.1016/j.bcp.2008.12.017. Epub 2009 Jan 6. [PubMed:19185566]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
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.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
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. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19. [PubMed:18713951]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Peptide:proton symporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name
SLC15A2
Uniprot ID
Q16348
Uniprot Name
Solute carrier family 15 member 2
Molecular Weight
81782.77 Da
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. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19. [PubMed:18713951]

Drug created on June 13, 2005 07:24 / Updated on December 18, 2018 09:08