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Spirapril

July 24, 2017
Common Name

Spirapril Description

Spirapril is an ACE inhibitor antihypertensive drug used to treat hypertension. Like many ACE inhibitors, this is a prodrug which is converted to the active metabolite spiraprilat following oral administration. ACE inhibitors are used primarily in treatment of hypertension and congestive heart failure. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source QuadroprilMeSH RenpressMeSH Spirapril hydrochlorideMeSH RenormaxMeSH

Chemical Formlia

C22H30N2O5S2 Average Molecliar Weight

466.614 Monoisotopic Molecliar Weight

466.15961346 IUPAC Name

(8S)-7-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid Traditional Name

spirapril CAS Registry Number

83647-97-6 SMILES

CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2(C[C@H]1C(O)=O)SCCS2

InChI Identifier

InChI=1S/C22H30N2O5S2/c1-3-29-21(28)17(10-9-16-7-5-4-6-8-16)23-15(2)19(25)24-14-22(30-11-12-31-22)13-18(24)20(26)27/h4-8,15,17-18,23H,3,9-14H2,1-2H3,(H,26,27)/t15-,17-,18-/m0/s1

InChI Key

HRWCVUIFMSZDJS-SZMVWBNQSA-N Chemical Taxonomy Description

This compound 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. Kingdom

Organic compounds Super Class

Organic acids and derivatives Class

Carboxylic acids and derivatives Sub Class

Amino acids, peptides, and analogues Direct Parent

Dipeptides Alternative Parents

  • N-acyl-L-alpha-amino acids
  • Alpha amino acid esters
  • Alpha amino acid amides
  • Pyrrolidine carboxylic acids
  • N-acylpyrrolidines
  • Fatty acid esters
  • Dithioketals
  • Aralkylamines
  • Dicarboxylic acids and derivatives
  • Benzene and substituted derivatives
  • Tertiary carboxylic acid amides
  • 1,3-dithiolanes
  • Amino acids
  • Carboxylic acid esters
  • Dialkylthioethers
  • Dialkylamines
  • Azacyclic compounds
  • Carboxylic acids
  • Organic oxides
  • Hydrocarbon derivatives
  • Organopnictogen compounds
  • Carbonyl compounds

    • Substituents

  • Alpha-dipeptide
  • Alpha-amino acid ester
  • N-acyl-alpha-amino acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-l-alpha-amino acid
  • Alpha-amino acid amide
  • Alpha-amino acid or derivatives
  • N-acylpyrrolidine
  • Pyrrolidine carboxylic acid
  • Pyrrolidine carboxylic acid or derivatives
  • Fatty acid ester
  • Aralkylamine
  • Dithioketal
  • Monocyclic benzene moiety
  • Fatty acyl
  • Dicarboxylic acid or derivatives
  • Benzenoid
  • Pyrrolidine
  • Dithiolane
  • Tertiary carboxylic acid amide
  • Thioacetal
  • 1,3-dithiolane
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Amino acid
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid
  • Secondary aliphatic amine
  • Dialkylthioether
  • Thioether
  • Secondary amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Organopnictogen compound
  • Amine
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Angiotensin-converting Enzyme Inhibitors
  • Antihypertensive Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility2.93e-02 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.029 mg/mLALOGPS logP1.79ALOGPS logP1.6ChemAxon logS-4.2ALOGPS pKa (Strongest Acidic)3.62ChemAxon pKa (Strongest Basic)5.2ChemAxon Physiological Charge-1ChemAxon Hydrogen Acceptor Count5ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area95.94 Å2ChemAxon Rotatable Bond Count10ChemAxon Refractivity121.94 m3·mol-1ChemAxon Polarizability48.74 Å3ChemAxon Number of Rings3ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Extracellliar
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link Spirapril Metabolism PathwaySMP00598Not Available Spirapril PathwaySMP00156Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01348

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01348

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01348 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    4470933 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Spirapril NuGOwiki Link

    HMDB15438 Metagene Link

    HMDB15438 METLIN ID

    Not Available PubChem Compound

    5311447 PDB ID

    Not Available ChEBI ID

    101967

    Product: Lercanidipine

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. 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 ]
    2. 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 ]
    3. Noble S, Sorkin EM: Spirapril. A preliminary review of its pharmacology and therapeutic efficacy in the treatment of hypertension. Drugs. 1995 May;49(5):750-66. [PubMed:7601014 ]
    4. Shohat J, Wittenberg C, Erman A, Rosenfeld J, Boner G: Acute and chronic effects of spirapril, alone or in combination with isradipine on kidney function and blood pressure in patients with reduced kidney function and hypertension. Scand J Urol Nephrol. 1999 Feb;33(1):57-62. [PubMed:10100366 ]

    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. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. [PubMed:11929321 ]
    2. Maul B, Krause W, Pankow K, Becker M, Gembardt F, Alenina N, Walther T, Bader M, Siems WE: Central angiotensin II controls alcohol consumption via its AT1 receptor. FASEB J. 2005 Sep;19(11):1474-81. [PubMed:16126915 ]
    3. Hermida RC, Ayala DE, Fontao MJ, Mojon A, Alonso I, Fernandez JR: Administration-time-dependent effects of spirapril on ambulatory blood pressure in uncomplicated essential hypertension. Chronobiol Int. 2010 May;27(3):560-74. doi: 10.3109/07420528.2010.485411. [PubMed:20524801 ]
    4. Arend U, Albrecht S, Meisel E, Schmidt J: [Influence of ACE inhibitor spirapril on left ventricular hypertrophy]. Fortschr Med Orig. 2002 Dec 5;120(4):147-50. [PubMed:12613273 ]
    5. 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 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 ]

    PMID: 25055869

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