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Showing drug card for Cilazapril (DB01340)

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Version 2.5
Creation Date 2007-06-30 18:09:29
Update Date 2009-06-23 18:08:22
Primary Accession Number DB01340
Secondary Accession Number Not Available
Name Cilazapril
Drug Type
  • Approved
  • Small Molecule
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]
Synonyms Not Available
Brand Names Not Available
Brand Mixtures Not Available
Chemical IUPAC Name (1S,9S)-9-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-10-oxo-1,2,3,4,6,7,8,9-octahydropyridazino[1,2-a]diazepine-1-carboxylic acid hydrate
Chemical Formula C22H33N3O6
Chemical Structure Structure
CAS Registry Number 92077-78-6
InChI Identifier InChI=1/C22H31N3O5.H2O/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);1H2/t17-,18-,19-;/m0./s1/f/h27H;
InChI Key JQRZBPFGBRIWSN-OHVQNRRIDW
KEGG Drug Not Available
KEGG Compound Not Available
PubChem Compound 56329 Link Image
PubChem Substance 193657 Link Image
ChEBI ID Not Available
PharmGKB ID PA10315 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 01911465 Link Image
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Cilazapril Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 435.5139
Monoisotopic Molecular Weight 435.2369
State Solid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility Not Available Calculated using ALOGPS
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP Not Available Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS Not Available Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES O.CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=O
Canonical SMILES O.CCOC(=O)C(CCC1=CC=CC=C1)NC1CCCN2CCCC(N2C1=O)C(O)=O
Drug Category
  • Angiotensin-converting Enzyme Inhibitors
  • Antihypertensive Agents
ATC Codes
AHFS Codes
  • 24:32.04
Indication Not Available
Pharmacology Not Available
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
Toxicity Not Available
Protein Binding Not Available
Biotransformation Not Available
Half Life Not Available
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Not Available
Interactions Not Available
Drug Interactions
Drug Interaction
Amiloride Increased risk of hyperkaliemia
Drospirenone Increased risk of hyperkaliemia
Lithium The ACE inhibitor increases serum levels of lithium
Potassium Increased risk of hyperkaliemia
Spironolactone Increased risk of hyperkaliemia
Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
Triamterene Increased risk of hyperkaliemia
Food Interactions
  • Food decreases cilazapril absorption with no significant clinical impact.
  • Take without regard to meals.
Pathways
Name SMPDB Link KEGG Link
Cilazapril Pathway SMP00147 Link Image
General References
  1. Wikipedia Link Image
Organisms Affected Not Available
Targets
  1. Angiotensinogen
Drug Target 1 [top]
Target 1 ID 1694
Target 1 Name Angiotensinogen
Target 1 Synonyms
  1. Angiotensinogen precursor
  2. Serpin A8
Target 1 Gene Name AGT
Target 1 Protein Sequence >Angiotensinogen precursor 
MRKRAPQSEMAPAGVSLRATILCLLAWAGLAAGDRVYIHPFHLVIHNESTCEQLAKANAG
KPKDPTFIPAPIQAKTSPVDEKALQDQLVLVAAKLDTEDKLRAAMVGMLANFLGFRIYGM
HSELWGVVHGATVLSPTAVFGTLASLYLGALDHTADRLQAILGVPWKDKNCTSRLDAHKV
LSALQAVQGLLVAQGRADSQAQLLLSTVVGVFTAPGLHLKQPFVQGLALYTPVVLPRSLD
FTELDVAAEKIDRFMQAVTGWKTGCSLMGASVDSTLAFNTYVHFQGKMKGFSLLAEPQEF
WVDNSTSVSVPMLSGMGTFQHWSDIQDNFSVTQVPFTESACLLLIQPHYASDLDKVEGLT
FQQNSLNWMKKLSPRTIHLTMPQLVLQGSYDLQDLLAQAELPAILHTELNLQKLSNDRIR
VGEVLNSIFFELEADEREPTESTQQLNKPEVLEVTLNRPFLFAVYDQSATALHFLGRVAN
PLSTA
Target 1 Number of Residues 493
Target 1 Molecular Weight 53155
Target 1 Theoretical pI 6.27
Target 1 GO Classification
Function
enzyme regulator activity
enzyme inhibitor activity
protease inhibitor activity
endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
Process
Not Available
Component
Not Available
Target 1 General Function Involved in serine-type endopeptidase inhibitor activity
Target 1 Specific Function Angiotensin-3 stimulates aldosterone release
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-33
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 178640 Link Image
Target 1 UniProtKB/Swiss-Prot ID P01019 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ANGT_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Secreted protein
Target 1 Gene Sequence >1458 bp 
ATGCGGAAGCGAGCACCCCAGTCTGAGATGGCTCCTGCCGGTGTGAGCCTGAGGGCCACC
ATCCTCTGCCTCCTGGCCTGGGCTGGCCTGGCTGCAGGTGACCGGGTGTACATACACCCC
TTCCACCTCGTCATCCACAATGAGAGTACCTGTGAGCAGCTGGCAAAGGCCAATGCCGGG
AAGCCCAAAGACCCCACCTTCATACCTGCTCCAATTCAGGCCAAGACATCCCCTGTGGAT
GAAAAGGCCCTACAGGACCAGCTGGTGCTAGTCGCTGCAAAACTTGACACCGAAGACAAG
TTGAGGGCCGCAATGGTCGGGATGCTGGCCAACTTCTTGGGCTTCCGTATATATGGCATG
CACAGTGAGCTATGGGGCGTGGTCCATGGGGCCACCGTCCTCTCCCCAACGGCTGTCTTT
GGCACCCTGGCCTCTCTCTATCTGGGAGCCTTGGACCACACAGCTGACAGGCTACAGGCA
ATCCTGGGTGTTCCTTGGAAGGACAAGAACTGCACCTCCCGGCTGGATGCGCACAAGGTC
CTGTCTGCCCTGCAGGCTGTACAGGGCCTGCTAGTGGCCCAGGGCAGGGCTGATAGCCAG
GCCCAGCTGCTGCTGTCCACGGTGGTGGGCGTGTTCACAGCCCCAGGCCTGCACCTGAAG
CAGCCGTTTGTGCAGGGCCTGGCTCTCTATACCCCTGTGGTCCTCCCACGCTCTCTGGAC
TTCACAGAACTGGATGTTGCTGCTGAGAAGATTGACAGGTTCATGCAGGCTGTGACAGGA
TGGAAGACTGGCTGCTCCCTGATGGGAGCCAGTGTGGACAGCACCCTGGCTTTCAACACC
TACGTCCACTTCCAAGGGAAGATGAAGGGCTTCTCCCTGCTGGCCGAGCCCCAGGAGTTC
TGGGTGGACAACAGCACCTCAGTGTCTGTTCCCATGCTCTCTGGCATGGGCACCTTCCAG
CACTGGAGTGACATCCAGGACAACTTCTCGGTGACTCAAGTGCCCTTCACTGAGAGCGCC
TGCCTGCTGCTGATCCAGCCTCACTATGCCTCTGACCTGGACAAGGTGGAGGGTCTCACT
TTCCAGCAAAACTCCCTCAACTGGATGAAGAAACTGTCTCCCCGGACCATCCACCTGACC
ATGCCCCAACTGGTGCTGCAAGGATCTTATGACCTGCAGGACCTGCTCGCCCAGGCTGAG
CTGCCCGCCATTCTGCACACCGAGCTGAACCTGCAAAAATTGAGCAATGACCGCATCAGG
GTGGGGGAGGTGCTGAACAGCATTTTTTTTGAGCTTGAAGCGGATGAGAGAGAGCCCACA
GAGTCTACCCAACAGCTTAACAAGCCTGAGGTCTTGGAGGTGACCCTGAACCGCCCATTC
CTGTTTGCTGTGTATGATCAAAGCGCCACTGCCCTGCACTTCCTGGGCCGCGTGGCCAAC
CCGCTGAGCACAGCATGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID AGT Link Image
Target 1 GenAtlas ID AGT Link Image
Target 1 HGNC ID HGNC:333 Link Image
Target 1 Chromosome Location 1
Target 1 Locus 1q42-q43
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Goodfriend TL, Peach MJ: Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system. Circ Res. 1975 Jun;36(6 Suppl 1):38-48. [PubMed Link Image]
  2. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, et al.: Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992 Oct 2;71(1):169-80. [PubMed Link Image]
  3. Fukamizu A, Takahashi S, Seo MS, Tada M, Tanimoto K, Uehara S, Murakami K: Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter. J Biol Chem. 1990 May 5;265(13):7576-82. [PubMed Link Image]
  4. Kunapuli SP, Kumar A: Molecular cloning of human angiotensinogen cDNA and evidence for the presence of its mRNA in rat heart. Circ Res. 1987 May;60(5):786-90. [PubMed Link Image]
  5. Gaillard I, Clauser E, Corvol P: Structure of human angiotensinogen gene. DNA. 1989 Mar;8(2):87-99. [PubMed Link Image]
  6. Kunapuli SP, Benedict CR, Kumar A: Tissue specific hormonal regulation of the rat angiotensinogen gene expression. Arch Biochem Biophys. 1987 May 1;254(2):642-6. [PubMed Link Image]
  7. Campbell DJ, Bouhnik J, Coezy E, Menard J, Corvol P: Processing of rat and human angiotensinogen precursors by microsomal membranes. Mol Cell Endocrinol. 1985 Nov;43(1):31-40. [PubMed Link Image]
  8. Arakawa K, Minohara A, Yamada J, Nakamura M: Enzymatic degradation and electrophoresis of human angiotensin I. Biochim Biophys Acta. 1968 Sep 10;168(1):106-12. [PubMed Link Image]
  9. Kageyama R, Ohkubo H, Nakanishi S: Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. Biochemistry. 1984 Jul 31;23(16):3603-9. [PubMed Link Image]
  10. Tewksbury DA, Dart RA, Travis J: The amino terminal amino acid sequence of human angiotensinogen. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1311-5. [PubMed Link Image]
  11. 7539791 Oxvig C, Haaning J, Kristensen L, Wagner JM, Rubin I, Stigbrand T, Gleich GJ, Sottrup-Jensen L: Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma. J Biol Chem. 1995 Jun 9;270(23):13645-51.
  12. 7607642 Hixson JE, Powers PK: Detection and characterization of new mutations in the human angiotensinogen gene (AGT). Hum Genet. 1995 Jul;96(1):110-2.
  13. 7744780 Inoue I, Rohrwasser A, Helin C, Jeunemaitre X, Crain P, Bohlender J, Lifton RP, Corvol P, Ward K, Lalouel JM: A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system. J Biol Chem. 1995 May 12;270(19):11430-6.
  14. 8513325 Ward K, Hata A, Jeunemaitre X, Helin C, Nelson L, Namikawa C, Farrington PF, Ogasawara M, Suzumori K, Tomoda S, et al.: A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet. 1993 May;4(1):59-61.
  15. 8621667 Gimenez-Roqueplo AP, Leconte I, Cohen P, Simon D, Guyene TT, Celerier J, Pau B, Corvol P, Clauser E, Jeunemaitre X: The natural mutation Y248C of human angiotensinogen leads to abnormal glycosylation and altered immunological recognition of the protein. J Biol Chem. 1996 Apr 19;271(16):9838-44.
  16. 9492317 Carpenter KA, Wilkes BC, Schiller PW: The octapeptide angiotensin II adopts a well-defined structure in a phospholipid environment. Eur J Biochem. 1998 Jan 15;251(1-2):448-53.
Target 1 Drug 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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]

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.