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Identification
NameCilazapril
Accession NumberDB01340
Typesmall molecule
Groupsapproved
Description

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]

Structure
Thumb
Synonyms
SynonymLanguageCode
InhibaceNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number92077-78-6
WeightAverage: 417.4986
Monoisotopic: 417.226371117
Chemical FormulaC22H31N3O5
InChI KeyHHHKFGXWKKUNCY-FHWLQOOXSA-N
InChI
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
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
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acid Esters
Alternative parentsPhenylpropylamines; Fatty Acid Esters; Diazinanes; Pyridazines and Derivatives; Dicarboxylic Acids and Derivatives; Carboxylic Acid Esters; Carboxylic Acid Hydrazides; Enolates; Ethers; Dialkylamines; Polyamines; Carboxylic Acid Amides; Carboxylic Acids; Hydrazines and Derivatives
Substituentsphenylpropylamine; fatty acid ester; 1,2-diazinane; dicarboxylic acid derivative; benzene; pyridazine; carboxylic acid ester; carboxamide group; carboxylic acid hydrazide; secondary aliphatic amine; polyamine; secondary amine; enolate; ether; carboxylic acid; hydrazine derivative; organonitrogen compound; amine
Classification descriptionThis compound belongs to the alpha amino acid esters. These are ester derivatives of alpha amino acids.
Pharmacology
IndicationCilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure.
PharmacodynamicsCilazapril inhibits the production angiotensin II. By doing so, it decreases sodium and water reabsorption (via aldosterone) and it decreases vasoconstriction. The combined effect of this is a decrease in vascular resistance, and therefore, blood pressure.
Mechanism of actionCilazapril is a pyridazine ACE inhibitor. It 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
SubstrateEnzymesProduct
Cilazapril
Not Available
CilazaprilatDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
Pathways
PathwayCategorySMPDB ID
Cilazapril Action PathwayDrug actionSMP00147
Cilazapril Metabolism PathwayDrug metabolismSMP00592
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9157
Blood Brain Barrier - 0.9402
Caco-2 permeable - 0.7698
P-glycoprotein substrate Substrate 0.8727
P-glycoprotein inhibitor I Inhibitor 0.7775
P-glycoprotein inhibitor II Non-inhibitor 0.8788
Renal organic cation transporter Non-inhibitor 0.8318
CYP450 2C9 substrate Non-substrate 0.7876
CYP450 2D6 substrate Non-substrate 0.8283
CYP450 3A4 substrate Substrate 0.5396
CYP450 1A2 substrate Non-inhibitor 0.882
CYP450 2C9 substrate Non-inhibitor 0.7804
CYP450 2D6 substrate Non-inhibitor 0.7503
CYP450 2C19 substrate Non-inhibitor 0.816
CYP450 3A4 substrate Non-inhibitor 0.8201
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8376
Ames test Non AMES toxic 0.6023
Carcinogenicity Non-carcinogens 0.9028
Biodegradation Not ready biodegradable 0.9942
Rat acute toxicity 2.3700 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9311
hERG inhibition (predictor II) Inhibitor 0.6303
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Inhibace 5 mg Tablet0.94USDtablet
Inhibace 2.5 mg Tablet0.81USDtablet
Inhibace 1 mg Tablet0.7USDtablet
Apo-Cilazapril 5 mg Tablet0.52USDtablet
Co Cilazapril 5 mg Tablet0.52USDtablet
Mylan-Cilazapril 5 mg Tablet0.52USDtablet
Novo-Cilazapril 5 mg Tablet0.52USDtablet
Pms-Cilazapril 5 mg Tablet0.52USDtablet
Apo-Cilazapril 2.5 mg Tablet0.45USDtablet
Co Cilazapril 2.5 mg Tablet0.45USDtablet
Mylan-Cilazapril 2.5 mg Tablet0.45USDtablet
Novo-Cilazapril 2.5 mg Tablet0.45USDtablet
Pms-Cilazapril 2.5 mg Tablet0.45USDtablet
Apo-Cilazapril 1 mg Tablet0.39USDtablet
Mylan-Cilazapril 1 mg Tablet0.39USDtablet
Novo-Cilazapril 1 mg Tablet0.39USDtablet
Pms-Cilazapril 1 mg Tablet0.39USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility1.06e+00 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 area99.18ChemAxon
rotatable bond count9ChemAxon
refractivity110.56ChemAxon
polarizability44.73ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Yatendra Kumar, Mohan Prasad, Kaptan Singh, Kintali Ramana, Surendra Dhingra, “Enantiomerically pure cilazapril, process for preparation.” U.S. Patent US20060293517, issued December 28, 2006.

US20060293517
General ReferenceNot Available
External Links
ResourceLink
Therapeutic Targets DatabaseDAP000912
PharmGKBPA164748302
Drug Product Database1911465
WikipediaCilazapril
ATC CodesC09AA08
AHFS Codes
  • 24:32.04
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmilorideIncreased risk of hyperkalemia
DrospirenoneIncreased risk of hyperkalemia
LithiumThe ACE inhibitor increases serum levels of lithium
PotassiumIncreased risk of hyperkalemia
SpironolactoneIncreased risk of hyperkalemia
TizanidineTizanidine increases the risk of hypotension with the ACE inhibitor
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TriamtereneIncreased risk of hyperkalemia
Food Interactions
  • Food decreases cilazapril absorption with no significant clinical impact.
  • Take without regard to meals.

Targets

1. Angiotensin-converting enzyme

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Angiotensin-converting enzyme P12821 Details

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
  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
  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
  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
  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
  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. Epub 2008 Apr 18. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

2. Solute carrier family 15 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 15 member 1 P46059 Details

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

3. Solute carrier family 15 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 15 member 2 Q16348 Details

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

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Drug created on June 30, 2007 12:09 / Updated on September 16, 2013 17:14