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Identification
Name Cilazapril
Accession Number DB01340
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Inhibace
Brand names Not Available
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • Angiotensin-converting Enzyme Inhibitors
CAS number 92077-78-6
Weight Average: 417.4986
Monoisotopic: 417.226371117
Chemical Formula C22H31N3O5
InChI Key InChIKey=HHHKFGXWKKUNCY-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication Cilazapril is an ACE inhibtor class drug used in the treatment of hypertension and heart failure.
Pharmacodynamics Cilazapril 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 action Cilazapril 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms Not Available
Pathways
Pathway Name SMPDB ID
Smp00147 Cilazapril Pathway SMP00147
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Inhibace 5 mg Tablet 0.94 USD tablet
Inhibace 2.5 mg Tablet 0.81 USD tablet
Inhibace 1 mg Tablet 0.7 USD tablet
Apo-Cilazapril 5 mg Tablet 0.52 USD tablet
Co Cilazapril 5 mg Tablet 0.52 USD tablet
Mylan-Cilazapril 5 mg Tablet 0.52 USD tablet
Novo-Cilazapril 5 mg Tablet 0.52 USD tablet
Pms-Cilazapril 5 mg Tablet 0.52 USD tablet
Apo-Cilazapril 2.5 mg Tablet 0.45 USD tablet
Co Cilazapril 2.5 mg Tablet 0.45 USD tablet
Mylan-Cilazapril 2.5 mg Tablet 0.45 USD tablet
Novo-Cilazapril 2.5 mg Tablet 0.45 USD tablet
Pms-Cilazapril 2.5 mg Tablet 0.45 USD tablet
Apo-Cilazapril 1 mg Tablet 0.39 USD tablet
Mylan-Cilazapril 1 mg Tablet 0.39 USD tablet
Novo-Cilazapril 1 mg Tablet 0.39 USD tablet
Pms-Cilazapril 1 mg Tablet 0.39 USD tablet
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 1.06e+00 g/l ALOGPS
logP -0.20 ALOGPS
logP -0.08 ChemAxon Molconvert
logS -2.59 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 99.18 ChemAxon Molconvert
rotatable bond count 9 ChemAxon Molconvert
refractivity 110.56 ChemAxon Molconvert
polarizability 44.73 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
Therapeutic Targets Database DAP000912 Link_out
PharmGKB PA10315 Link_out
Drug Product Database 1911465 Link_out
Wikipedia http://en.wikipedia.org/wiki/Cilazapril Link_out
ATC Codes
  • C09AA08
AHFS Codes
  • 24:32.04
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Food decreases cilazapril absorption with no significant clinical impact.
  • Take without regard to meals.
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. 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

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. 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

3. 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 30, 2007 12:09 / Updated on November 23, 2010 08:06

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.