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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:51:59 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
Data?1582753297
Synonyms
ValueSource
Cilazapril anhydrousChEBI
CilazaprilumChEBI
DynormChEBI
InhibaceChEBI
Ro 34-2848ChEBI
VascaceChEBI
VascaseChEBI
Monohydrate, cilazaprilHMDB
Cilazapril monohydrateHMDB
Cilazapril, (s*)-isomerHMDB
Hydrate, cilazaprilHMDB
Anhydrous, cilazaprilHMDB
Cilazapril hydrateHMDB
Cilazapril monohydrobromideHMDB
Cilazapril, anhydrousHMDB
Monohydrobromide, cilazaprilHMDB
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
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
  • 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
Physiological effectNot Available
Disposition
Process
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.06 g/LNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular 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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+193.66931661259
DarkChem[M-H]-191.14431661259
DeepCCS[M+H]+199.66130932474
DeepCCS[M-H]-197.26630932474
DeepCCS[M-2H]-230.14730932474
DeepCCS[M+Na]+205.67730932474
AllCCS[M+H]+200.032859911
AllCCS[M+H-H2O]+197.732859911
AllCCS[M+NH4]+202.132859911
AllCCS[M+Na]+202.832859911
AllCCS[M-H]-196.232859911
AllCCS[M+Na-2H]-197.032859911
AllCCS[M+HCOO]-198.032859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
CilazaprilCCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O4294.6Standard polar33892256
CilazaprilCCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O3052.8Standard non polar33892256
CilazaprilCCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O3264.7Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Cilazapril,1TMS,isomer #1CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@@H](C(=O)O[Si](C)(C)C)N2C1=O3218.5Semi standard non polar33892256
Cilazapril,1TMS,isomer #2CCOC(=O)[C@H](CCC1=CC=CC=C1)N([C@H]1CCCN2CCC[C@@H](C(=O)O)N2C1=O)[Si](C)(C)C3246.6Semi standard non polar33892256
Cilazapril,2TMS,isomer #1CCOC(=O)[C@H](CCC1=CC=CC=C1)N([C@H]1CCCN2CCC[C@@H](C(=O)O[Si](C)(C)C)N2C1=O)[Si](C)(C)C3208.7Semi standard non polar33892256
Cilazapril,2TMS,isomer #1CCOC(=O)[C@H](CCC1=CC=CC=C1)N([C@H]1CCCN2CCC[C@@H](C(=O)O[Si](C)(C)C)N2C1=O)[Si](C)(C)C3099.1Standard non polar33892256
Cilazapril,2TMS,isomer #1CCOC(=O)[C@H](CCC1=CC=CC=C1)N([C@H]1CCCN2CCC[C@@H](C(=O)O[Si](C)(C)C)N2C1=O)[Si](C)(C)C4502.7Standard polar33892256
Cilazapril,1TBDMS,isomer #1CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@@H](C(=O)O[Si](C)(C)C(C)(C)C)N2C1=O3439.7Semi standard non polar33892256
Cilazapril,1TBDMS,isomer #2CCOC(=O)[C@H](CCC1=CC=CC=C1)N([C@H]1CCCN2CCC[C@@H](C(=O)O)N2C1=O)[Si](C)(C)C(C)(C)C3463.7Semi standard non polar33892256
Cilazapril,2TBDMS,isomer #1CCOC(=O)[C@H](CCC1=CC=CC=C1)N([C@H]1CCCN2CCC[C@@H](C(=O)O[Si](C)(C)C(C)(C)C)N2C1=O)[Si](C)(C)C(C)(C)C3648.4Semi standard non polar33892256
Cilazapril,2TBDMS,isomer #1CCOC(=O)[C@H](CCC1=CC=CC=C1)N([C@H]1CCCN2CCC[C@@H](C(=O)O[Si](C)(C)C(C)(C)C)N2C1=O)[Si](C)(C)C(C)(C)C3482.3Standard non polar33892256
Cilazapril,2TBDMS,isomer #1CCOC(=O)[C@H](CCC1=CC=CC=C1)N([C@H]1CCCN2CCC[C@@H](C(=O)O[Si](C)(C)C(C)(C)C)N2C1=O)[Si](C)(C)C(C)(C)C4557.7Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Cilazapril GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-3119000000-cf816839d9e62aaeb51d2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Cilazapril GC-MS (1 TMS) - 70eV, Positivesplash10-014i-3100900000-8a98b7cfd4306c863f3b2017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Cilazapril GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Cilazapril GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 10V, Positive-QTOFsplash10-014i-0114900000-46b169656e56da84df002016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 20V, Positive-QTOFsplash10-00r6-3339300000-597e65efc2ccd4259fc62016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 40V, Positive-QTOFsplash10-0006-7930000000-01cd40a3307d1d9136e12016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 10V, Negative-QTOFsplash10-0100-2609400000-2b63f9aade5f2408e90c2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 20V, Negative-QTOFsplash10-00fs-2029000000-ef46b50c866af838f6d52016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 40V, Negative-QTOFsplash10-000i-9413000000-bf81f08b26484eff95d02016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 10V, Positive-QTOFsplash10-014i-0001900000-2155fa52bd310940aaa12021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 20V, Positive-QTOFsplash10-00kf-0129300000-d64d5ab791860881b4052021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 40V, Positive-QTOFsplash10-0560-5901000000-8c919145e29e13e6d8042021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 10V, Negative-QTOFsplash10-014i-0001900000-13fb2fadf7c261ea1f972021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 20V, Negative-QTOFsplash10-014l-3289700000-05092f6b096b7ae757aa2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cilazapril 40V, Negative-QTOFsplash10-0019-2982000000-4f5dadbd2ce238e96eef2021-10-11Wishart LabView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Predicted 1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01340 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01340 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01340
Phenol Explorer Compound IDNot Available
FooDB 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
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
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 ]