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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2017-10-23 19:06:31 UTC
HMDB IDHMDB0015433
Secondary Accession Numbers
  • HMDB15433
Metabolite Identification
Common NameCilazapril
DescriptionCilazapril is only found in individuals that have used or taken this drug. It is one of the angiotensin-converting enzyme inhibitors (ACE inhibitors) used for hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. [PubChem]Cilazapri, as a pyridazine ACE inhibitor, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. As angiotensin II is a vasoconstrictor and a negative feedback mediator for renin activity, lower angiotensin II levels results in a decrease in blood pressure, an increase in renin activity, and stimulation of baroreceptor reflex mechanisms. Kininase II, an enzyme which degrades the vasodilator bradykinin, is identical to ACE and may also be inhibited.
Structure
Thumb
Synonyms
ValueSource
InhibaceKegg
Cilazapril anhydrousMeSH
Monohydrate, cilazaprilMeSH
Cilazapril monohydrateMeSH
Cilazapril, (s*)-isomerMeSH
Hydrate, cilazaprilMeSH
Anhydrous, cilazaprilMeSH
Cilazapril hydrateMeSH
Cilazapril monohydrobromideMeSH
Cilazapril, anhydrousMeSH
Monohydrobromide, cilazaprilMeSH
Chemical FormulaC22H31N3O5
Average Molecular Weight417.4986
Monoisotopic Molecular Weight417.226371117
IUPAC Name(1S,9S)-9-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}-10-oxo-octahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid
Traditional Nameinhibace
CAS Registry Number92077-78-6
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O
InChI Identifier
InChI=1S/C22H31N3O5/c1-2-30-22(29)18(13-12-16-8-4-3-5-9-16)23-17-10-6-14-24-15-7-11-19(21(27)28)25(24)20(17)26/h3-5,8-9,17-19,23H,2,6-7,10-15H2,1H3,(H,27,28)/t17-,18-,19-/m0/s1
InChI KeyHHHKFGXWKKUNCY-FHWLQOOXSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboxylic acids and derivatives
Direct ParentDipeptides
Alternative Parents
Substituents
  • Alpha-dipeptide
  • Alpha-amino acid ester
  • Alpha-amino acid or derivatives
  • 1,2-diazepane
  • Fatty acid ester
  • Diazepane
  • Aralkylamine
  • Dicarboxylic acid or derivatives
  • 1,2-diazinane
  • Pyridazine
  • Benzenoid
  • Fatty acyl
  • Monocyclic benzene moiety
  • Carboxylic acid hydrazide
  • Amino acid
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid
  • Secondary aliphatic amine
  • Secondary amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Amine
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Industrial application:

  Pharmaceutical industry:

    Cardiovascular drug:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.06 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.06 g/LALOGPS
logP-0.2ALOGPS
logP-0.0079ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)3.41ChemAxon
pKa (Strongest Basic)5.35ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.18 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity110.56 m³·mol⁻¹ChemAxon
Polarizability44.73 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-3119000000-cf816839d9e62aaeb51dView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-014i-3100900000-8a98b7cfd4306c863f3bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0114900000-46b169656e56da84df00View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00r6-3339300000-597e65efc2ccd4259fc6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-7930000000-01cd40a3307d1d9136e1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0100-2609400000-2b63f9aade5f2408e90cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00fs-2029000000-ef46b50c866af838f6d5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000i-9413000000-bf81f08b26484eff95d0View in MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Cilazapril Metabolism PathwayPw000568Pw000568 greyscalePw000568 simpleNot Available
Cilazapril PathwayPw000225Pw000225 greyscalePw000225 simpleNot Available
Displaying all 2 entries
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01340 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01340 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01340
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID50831
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCilazapril
METLIN IDNot Available
PubChem Compound56330
PDB IDNot Available
ChEBI ID553655
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in metallopeptidase activity
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:
149713.7
References
  1. Yoshiyama M, Takeuchi K, Omura T, Kim S, Yamagishi H, Toda I, Teragaki M, Akioka K, Iwao H, Yoshikawa J: Effects of candesartan and cilazapril on rats with myocardial infarction assessed by echocardiography. Hypertension. 1999 Apr;33(4):961-8. [PubMed:10205231 ]
  2. Kihara M, Mitsui MK, Mitsui Y, Okuda K, Nakasaka Y, Takahashi M, Schmelzer JD: Altered vasoreactivity to angiotensin II in experimental diabetic neuropathy: role of nitric oxide. Muscle Nerve. 1999 Jul;22(7):920-5. [PubMed:10398211 ]
  3. Mervaala E, Dehmel B, Gross V, Lippoldt A, Bohlender J, Milia AF, Ganten D, Luft FC: Angiotensin-converting enzyme inhibition and AT1 receptor blockade modify the pressure-natriuresis relationship by additive mechanisms in rats with human renin and angiotensinogen genes. J Am Soc Nephrol. 1999 Aug;10(8):1669-80. [PubMed:10446934 ]
  4. Rosendorff C, Patton J, Radford HM, Kalliatakis B: Alpha-adrenergic and angiotensin II pressor sensitivity in hypertensive patients treated with an angiotensin-converting enzyme inhibitor. J Cardiovasc Pharmacol. 1992;19 Suppl 6:S105-9. [PubMed:1382157 ]
  5. Hannedouche T, Ikeni A, Marques LP, Natov S, Dechaux M, Schmitt F, Lacour B, Grunfeld JP: Renal effects of angiotensin II in normotensive subjects on short-term cilazapril treatment. J Cardiovasc Pharmacol. 1992;19 Suppl 6:S25-7. [PubMed:1382161 ]
  6. Tylicki L, Rutkowski P, Renke M, Larczynski W, Aleksandrowicz E, Lysiak-Szydlowska W, Rutkowski B: Triple pharmacological blockade of the renin-angiotensin-aldosterone system in nondiabetic CKD: an open-label crossover randomized controlled trial. Am J Kidney Dis. 2008 Sep;52(3):486-93. doi: 10.1053/j.ajkd.2008.02.297. Epub 2008 Apr 18. [PubMed:18423812 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [PubMed:11895100 ]
General function:
Involved in 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
Molecular weight:
78805.3
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 ]
General function:
Involved in transporter 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
Molecular weight:
81782.8
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 ]