Spirapril

Identification

Name

Spirapril

Accession Number

DB01348

Description

Spirapril is an ACE inhibitor antihypertensive drug used to treat hypertension. Spirapril is converted to the active spiraprilat after administration. ACE inhibitors are used primarily in treatment of hypertension and congestive heart failure.

Type

Small Molecule

Groups

Approved

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Spirapril (DB01348)

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Weight

Average: 466.614
Monoisotopic: 466.15961346

Chemical Formula

C₂₂H₃₀N₂O₅S₂

Synonyms

• Espirapril
• Spirapril
• Spiraprilum

External IDs

• Sch 33844

Pharmacology

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Indication

Spirapril is an ACE inhibitor class drug used to treat hypertension.

Contraindications & Blackbox Warnings

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Pharmacodynamics

Spirapril is an angiotensin-converting enzyme (ACE) inhibitor. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. By blocking ACE, spirapril decreases angiotensin II which is a vasoconstrictor and inducer of aldosterone. So by inhibiting the enzymes, aldosterone secreation is decreased (so less sodium is reabsorbed) and there is a decrease in vasoconstriction. Combined, this leades to a decrease in blood pressure.

Mechanism of action

Spiraprilat, the active metabolite of spirapril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Spiraprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.

Target	Actions	Organism
AAngiotensin-converting enzyme	inhibitor	Humans

Absorption

Bioavailability is 50% following oral administration.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic. Converted to spiraprilat following oral administration.

Hover over products below to view reaction partners

• Spirapril
  • Spiraprilat

Route of elimination

Not Available

Half-life

30 to 35 hours

Clearance

Not Available

Adverse Effects

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Toxicity

Not Available

Affected organisms

• Humans and other mammals

Pathways

Pathway	Category
Spirapril Action Pathway	Drug action
Spirapril Metabolism Pathway	Drug metabolism

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Acebutolol	The risk or severity of hyperkalemia can be increased when Acebutolol is combined with Spirapril.
Aceclofenac	The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Spirapril.
Acemetacin	The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Spirapril.
Acetylsalicylic acid	The therapeutic efficacy of Spirapril can be decreased when used in combination with Acetylsalicylic acid.
Agrostis gigantea pollen	The risk or severity of adverse effects can be increased when Spirapril is combined with Agrostis gigantea pollen.
Agrostis stolonifera pollen	The risk or severity of adverse effects can be increased when Spirapril is combined with Agrostis stolonifera pollen.
Alclofenac	The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Alclofenac is combined with Spirapril.
Aldesleukin	Aldesleukin may increase the hypotensive activities of Spirapril.
Alfentanil	Alfentanil may decrease the antihypertensive activities of Spirapril.
Alfuzosin	Alfuzosin may increase the hypotensive activities of Spirapril.

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Food Interactions

• Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice).
• Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
• Limit salt intake. Salt may attenuate the antihypertensive effect.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Spirapril hydrochloride	OCC25LM897	94841-17-5	CLDOLNORSLLQDI-OOAIBONUSA-N

International/Other Brands

Renormax

Categories

ATC Codes

C09AA11 — Spirapril

• C09AA — ACE inhibitors, plain
• C09A — ACE INHIBITORS, PLAIN
• C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
• C — CARDIOVASCULAR SYSTEM

Drug Categories

• Agents Acting on the Renin-Angiotensin System
• Agents causing angioedema
• Agents causing hyperkalemia
• Amino Acids, Peptides, and Proteins
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Cardiovascular Agents
• Dipeptides
• Enzyme Inhibitors
• Oligopeptides
• Peptides
• Protease Inhibitors

Chemical TaxonomyProvided by Classyfire

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

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Substituents

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

show 33 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Chemical Identifiers

UNII

96U2K78I3V

CAS number

83647-97-6

InChI Key

HRWCVUIFMSZDJS-SZMVWBNQSA-N

InChI

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

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

SMILES

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

References

General References

1. 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]
2. 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]
3. 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]
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]

External Links

Human Metabolome Database

HMDB0015438

KEGG Drug

D08529

PubChem Compound

5311447

PubChem Substance

46506126

ChemSpider

4470933

BindingDB

50017124

RxNav

36908

ChEBI

135756

ChEMBL

CHEMBL431

ZINC

ZINC000004217459

Therapeutic Targets Database

DAP000911

PharmGKB

PA164776913

Wikipedia

Spirapril

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	High Blood Pressure (Hypertension)	1
4	Recruiting	Treatment	Cardiovascular Disease (CVD) / Type 2 Diabetes Mellitus	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0293 mg/mL	ALOGPS
logP	1.79	ALOGPS
logP	1.6	ChemAxon
logS	-4.2	ALOGPS
pKa (Strongest Acidic)	3.62	ChemAxon
pKa (Strongest Basic)	5.2	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	95.94 Å2	ChemAxon
Rotatable Bond Count	10	ChemAxon
Refractivity	121.94 m3·mol-1	ChemAxon
Polarizability	48.74 Å3	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	-	0.5287
Blood Brain Barrier	-	0.9614
Caco-2 permeable	-	0.83
P-glycoprotein substrate	Substrate	0.8223
P-glycoprotein inhibitor I	Non-inhibitor	0.6938
P-glycoprotein inhibitor II	Non-inhibitor	0.7426
Renal organic cation transporter	Non-inhibitor	0.8836
CYP450 2C9 substrate	Non-substrate	0.833
CYP450 2D6 substrate	Non-substrate	0.8553
CYP450 3A4 substrate	Non-substrate	0.5658
CYP450 1A2 substrate	Non-inhibitor	0.8439
CYP450 2C9 inhibitor	Non-inhibitor	0.7259
CYP450 2D6 inhibitor	Non-inhibitor	0.8813
CYP450 2C19 inhibitor	Non-inhibitor	0.5956
CYP450 3A4 inhibitor	Inhibitor	0.5073
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.6331
Ames test	Non AMES toxic	0.8764
Carcinogenicity	Non-carcinogens	0.908
Biodegradation	Not ready biodegradable	0.9115
Rat acute toxicity	2.2396 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9961
hERG inhibition (predictor II)	Non-inhibitor	0.5579

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

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Details1. Angiotensin-converting enzyme

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Zinc ion binding

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...

Gene Name

ACE

Uniprot ID

P12821

Uniprot Name

Angiotensin-converting enzyme

Molecular Weight

149713.675 Da

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]

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Drug created on June 30, 2007 18:15 / Updated on June 12, 2020 16:51