Page last updated: 2024-11-07

spiraprilat

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

SCH 33861: RN given refers to (8S-(7(R*(R*)),8R*))-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

spiraprilat : An azaspiro compound that is spirapril in which the ethyl ester group has been hydrolysed to the corresponding carboxylic acid group. It is the active metabolite of the angiotensin-converting enzyme (ACE) inhibitor spirapril. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID3033702
CHEMBL ID579
CHEBI ID141522
SCHEMBL ID296504
MeSH IDM0206629

Synonyms (40)

Synonym
83602-05-5
D03775
spiraprilat (usan/inn)
spiraprilat
sch-33861
sch 33861
spirapril diacid
CHEMBL579 ,
spiraprilate
(8s)-7-((s)-n-((s)-1-carboxy-3-phenylpropyl)alanyl)-1,4-dithia-7-azaspiro(4.4)nonane-8-carboxylic acid
spiraprilatum
(8s)-7-[(2s)-2-{[(1s)-1-carboxy-3-phenylpropyl]amino}propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
7-[n-(1(s)-carboxy-3-phenylpropyl)-s-alanyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(s)-carboxylic acid
CHEBI:141522
7-[2-(1-carboxy-3-phenyl-propylamino)-propionyl]-1,4-dithia-7-aza-spiro[4.4]nonane-8-carboxylic acid (spiraprilat)
bdbm50017122
7-[2-(1-carboxy-3-phenyl-propylamino)-propionyl]-1,4-dithia-7-aza-spiro[4.4]nonane-8-carboxylic acid
unii-qs56v5y7ec
spiraprilic acid
qs56v5y7ec ,
spiraprilate [inn-french]
spiraprilat [usan:inn:ban]
spiraprilatum [inn-latin]
1,4-dithia-7-azaspiro(4.4)nonane-8-carboxylic acid, 7-(2-((1-carboxy-3-phenylpropyl)amino)-1-oxopropyl)-, (8s-(7(r*(r*)),8r*))-
1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylicacid, 7-[(2s)-2-[[(1s)-1-carboxy-3-phenylpropyl]amino]-1-oxopropyl]-, (8s)-
(7s)-8-[(2s)-2-[[(2s)-1-hydroxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-1,4-dithia-8-azaspiro[4.4]nonane-7-carboxylic acid
gtpl6576
SCHEMBL296504
spiraprilat [inn]
(2s)-3-((2s)-2-(((1s)-1-carboxy-3-phenyl-propyl)amino)propanoyl)-6,9-dithia-3-azaspiro(4.4)nonane-2-carboxylic acid
(8s)-7-((2s)-2-(((1s)-1-carboxy-3-phenylpropyl)amino)propanoyl)-1,4-dithia-7-azaspiro(4.4)nonane-8-carboxylic acid
spiraprilat [usan]
spirapril hydrochloride monohydrate impurity b [ep impurity]
spirapril diacid [mi]
DTXSID30232453
HY-121460
(8s)-7-[(2s)-2-[[(1s)-1-carboxy-3-phenylpropyl]amino]propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
Q7577792
CS-0082130
AKOS040746367

Research Excerpts

Pharmacokinetics

The elimination half-life of spiraprilat was not different. There was no evidence of accumulation in any of the groups. The pharmacokinetic parameters derived after single and multiple doses.

ExcerptReferenceRelevance
" However, there was no evidence of accumulation of spiraprilat in any of the groups as determined by the pharmacokinetic parameters derived after single and multiple doses."( Pharmacokinetics of spirapril in renal impairment.
Elliott, HL; Grass, P; Guitard, C; Meredith, PA, 1994
)
0.29
" Regression analysis of pharmacokinetic parameters C(max)ss (the maximum steady-state drug concentration in plasma during a dosing interval), Cl/f (total plasma clearance) and k (elimination rate constant) of spirapril on creatinine clearance (Clcr) showed that the pharmacokinetics of spirapril were not significantly influenced by the degree of renal impairment."( Pharmacokinetics of spirapril and spiraprilat in patients with chronic renal failure.
Grass, P; Haufe, CC; Jansa, U; Sierakowski, B; Stein, G; Weidinger, G, 1994
)
0.29
" After intravenous infusion, the disposition of spirapril is monophasic with a terminal half-life of 20-50 minutes."( Spirapril: pharmacokinetic properties and drug interactions.
Gerbeau, C; Grass, P; Kutz, K, 1994
)
0.29
"00 h-1 in control subjects) while the elimination half-life of spiraprilat was not different."( Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease.
Grass, P; Krähenbühl, S; Kutz, K; Reichen, J; Surve, A, 1993
)
0.29

Bioavailability

The bioavailability of orally administered spirapril was 50% whereas the bioavailability. of spirapilat was virtually zero. The metabolite responsible for the pharmacological action of Spirapril is significantly reduced in patients.

ExcerptReferenceRelevance
" The bioavailability of orally administered spirapril was 50% whereas the bioavailability of orally administered spiraprilat was virtually zero."( Spirapril: pharmacokinetic properties and drug interactions.
Gerbeau, C; Grass, P; Kutz, K, 1994
)
0.29
" In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 micrograms."( Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease.
Grass, P; Krähenbühl, S; Kutz, K; Reichen, J; Surve, A, 1993
)
0.29

Dosage Studied

ExcerptRelevanceReference
" Regression analysis of pharmacokinetic parameters C(max)ss (the maximum steady-state drug concentration in plasma during a dosing interval), Cl/f (total plasma clearance) and k (elimination rate constant) of spirapril on creatinine clearance (Clcr) showed that the pharmacokinetics of spirapril were not significantly influenced by the degree of renal impairment."( Pharmacokinetics of spirapril and spiraprilat in patients with chronic renal failure.
Grass, P; Haufe, CC; Jansa, U; Sierakowski, B; Stein, G; Weidinger, G, 1994
)
0.29
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
antihypertensive agentAny drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitorAn EC 3.4.15.* (peptidyl-dipeptidase) inhibitor that interferes with the action of peptidyl-dipeptidase A (EC 3.4.15.1).
drug metabolitenull
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (7)

ClassDescription
azaspiro compoundAn azaspiro compound is a spiro compound in which at least one of the cyclic components is a nitrogen heterocyle.
dicarboxylic acidAny carboxylic acid containing two carboxy groups.
dipeptideAny molecule that contains two amino-acid residues connected by peptide linkages.
dithioketalA dithioacetal of formula R2C(SR')2, R =/= H, R' =/= H.
pyrrolidinecarboxylic acid
secondary amino compoundA compound formally derived from ammonia by replacing two hydrogen atoms by organyl groups.
tertiary carboxamideA carboxamide resulting from the formal condensation of a carboxylic acid with a secondary amine; formula RC(=O)NHR(1)R(2).
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (2)

PathwayProteinsCompounds
Spirapril Action Pathway34
Spirapril Metabolism Pathway12

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Angiotensin-converting enzyme Homo sapiens (human)IC50 (µMol)0.00080.00010.533610.0000AID38853
Angiotensin-converting enzymeRattus norvegicus (Norway rat)IC50 (µMol)0.00150.00090.33223.0300AID37962; AID38880
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (56)

Processvia Protein(s)Taxonomy
response to hypoxiaAngiotensin-converting enzyme Homo sapiens (human)
kidney developmentAngiotensin-converting enzyme Homo sapiens (human)
blood vessel remodelingAngiotensin-converting enzyme Homo sapiens (human)
angiotensin maturationAngiotensin-converting enzyme Homo sapiens (human)
regulation of renal output by angiotensinAngiotensin-converting enzyme Homo sapiens (human)
neutrophil mediated immunityAngiotensin-converting enzyme Homo sapiens (human)
antigen processing and presentation of peptide antigen via MHC class IAngiotensin-converting enzyme Homo sapiens (human)
regulation of systemic arterial blood pressure by renin-angiotensinAngiotensin-converting enzyme Homo sapiens (human)
proteolysisAngiotensin-converting enzyme Homo sapiens (human)
spermatogenesisAngiotensin-converting enzyme Homo sapiens (human)
female pregnancyAngiotensin-converting enzyme Homo sapiens (human)
regulation of blood pressureAngiotensin-converting enzyme Homo sapiens (human)
male gonad developmentAngiotensin-converting enzyme Homo sapiens (human)
response to xenobiotic stimulusAngiotensin-converting enzyme Homo sapiens (human)
embryo development ending in birth or egg hatchingAngiotensin-converting enzyme Homo sapiens (human)
post-transcriptional regulation of gene expressionAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of gene expressionAngiotensin-converting enzyme Homo sapiens (human)
substance P catabolic processAngiotensin-converting enzyme Homo sapiens (human)
bradykinin catabolic processAngiotensin-converting enzyme Homo sapiens (human)
regulation of smooth muscle cell migrationAngiotensin-converting enzyme Homo sapiens (human)
regulation of vasoconstrictionAngiotensin-converting enzyme Homo sapiens (human)
animal organ regenerationAngiotensin-converting enzyme Homo sapiens (human)
response to nutrient levelsAngiotensin-converting enzyme Homo sapiens (human)
response to lipopolysaccharideAngiotensin-converting enzyme Homo sapiens (human)
mononuclear cell proliferationAngiotensin-converting enzyme Homo sapiens (human)
response to laminar fluid shear stressAngiotensin-converting enzyme Homo sapiens (human)
angiotensin-activated signaling pathwayAngiotensin-converting enzyme Homo sapiens (human)
vasoconstrictionAngiotensin-converting enzyme Homo sapiens (human)
hormone metabolic processAngiotensin-converting enzyme Homo sapiens (human)
hormone catabolic processAngiotensin-converting enzyme Homo sapiens (human)
eating behaviorAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of apoptotic processAngiotensin-converting enzyme Homo sapiens (human)
peptide catabolic processAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of vasoconstrictionAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of glucose importAngiotensin-converting enzyme Homo sapiens (human)
regulation of synaptic plasticityAngiotensin-converting enzyme Homo sapiens (human)
lung alveolus developmentAngiotensin-converting enzyme Homo sapiens (human)
amyloid-beta metabolic processAngiotensin-converting enzyme Homo sapiens (human)
arachidonic acid secretionAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of neurogenesisAngiotensin-converting enzyme Homo sapiens (human)
heart contractionAngiotensin-converting enzyme Homo sapiens (human)
regulation of angiotensin metabolic processAngiotensin-converting enzyme Homo sapiens (human)
hematopoietic stem cell differentiationAngiotensin-converting enzyme Homo sapiens (human)
angiogenesis involved in coronary vascular morphogenesisAngiotensin-converting enzyme Homo sapiens (human)
cellular response to glucose stimulusAngiotensin-converting enzyme Homo sapiens (human)
response to dexamethasoneAngiotensin-converting enzyme Homo sapiens (human)
cell proliferation in bone marrowAngiotensin-converting enzyme Homo sapiens (human)
regulation of heart rate by cardiac conductionAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of calcium ion importAngiotensin-converting enzyme Homo sapiens (human)
response to thyroid hormoneAngiotensin-converting enzyme Homo sapiens (human)
blood vessel diameter maintenanceAngiotensin-converting enzyme Homo sapiens (human)
regulation of hematopoietic stem cell proliferationAngiotensin-converting enzyme Homo sapiens (human)
negative regulation of gap junction assemblyAngiotensin-converting enzyme Homo sapiens (human)
cellular response to aldosteroneAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of peptidyl-cysteine S-nitrosylationAngiotensin-converting enzyme Homo sapiens (human)
positive regulation of systemic arterial blood pressureAngiotensin-converting enzyme Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (16)

Processvia Protein(s)Taxonomy
endopeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
carboxypeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
metalloendopeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
calmodulin bindingAngiotensin-converting enzyme Homo sapiens (human)
peptidase activityAngiotensin-converting enzyme Homo sapiens (human)
metallopeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
exopeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
tripeptidyl-peptidase activityAngiotensin-converting enzyme Homo sapiens (human)
peptidyl-dipeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
zinc ion bindingAngiotensin-converting enzyme Homo sapiens (human)
chloride ion bindingAngiotensin-converting enzyme Homo sapiens (human)
mitogen-activated protein kinase kinase bindingAngiotensin-converting enzyme Homo sapiens (human)
bradykinin receptor bindingAngiotensin-converting enzyme Homo sapiens (human)
mitogen-activated protein kinase bindingAngiotensin-converting enzyme Homo sapiens (human)
metallodipeptidase activityAngiotensin-converting enzyme Homo sapiens (human)
heterocyclic compound bindingAngiotensin-converting enzyme Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (10)

Processvia Protein(s)Taxonomy
extracellular spaceAngiotensin-converting enzyme Homo sapiens (human)
extracellular regionAngiotensin-converting enzyme Homo sapiens (human)
extracellular spaceAngiotensin-converting enzyme Homo sapiens (human)
lysosomeAngiotensin-converting enzyme Homo sapiens (human)
endosomeAngiotensin-converting enzyme Homo sapiens (human)
plasma membraneAngiotensin-converting enzyme Homo sapiens (human)
external side of plasma membraneAngiotensin-converting enzyme Homo sapiens (human)
basal plasma membraneAngiotensin-converting enzyme Homo sapiens (human)
brush border membraneAngiotensin-converting enzyme Homo sapiens (human)
extracellular exosomeAngiotensin-converting enzyme Homo sapiens (human)
sperm midpieceAngiotensin-converting enzyme Homo sapiens (human)
plasma membraneAngiotensin-converting enzyme Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (16)

Assay IDTitleYearJournalArticle
AID38853Compound tested in vitro for inhibition of Angiotensin I converting enzyme1989Journal of medicinal chemistry, Jul, Volume: 32, Issue:7
Angiotensin converting enzyme inhibitors: spirapril and related compounds.
AID25867Ratio of biliary and urinary excretion of angiotensin converting enzyme inhibitors in male rat after intravenous dosing.1991Journal of medicinal chemistry, Jan, Volume: 34, Issue:1
Design, synthesis, and physicochemical properties of a novel, conformationally restricted 2,3-dihydro-1,3,4-thiadiazole-containing angiotensin converting enzyme inhibitor which is preferentially eliminated by the biliary route in rats.
AID26526Compound was tested for its maximum lipophilicity.1991Journal of medicinal chemistry, Jan, Volume: 34, Issue:1
Design, synthesis, and physicochemical properties of a novel, conformationally restricted 2,3-dihydro-1,3,4-thiadiazole-containing angiotensin converting enzyme inhibitor which is preferentially eliminated by the biliary route in rats.
AID38880Compound tested in vivo for inhibition of Angiotensin I converting enzyme in rat1989Journal of medicinal chemistry, Jul, Volume: 32, Issue:7
Angiotensin converting enzyme inhibitors: spirapril and related compounds.
AID182328% Inhibition of angiotensin-I induced pressor response in normotensive rats after peroral dosing of 15 umol/kg1988Journal of medicinal chemistry, Jun, Volume: 31, Issue:6
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.
AID25873The acid dissociation constant, pKa was determined. a'' represents value of C-terminus carboxylic acid.1991Journal of medicinal chemistry, Jan, Volume: 34, Issue:1
Design, synthesis, and physicochemical properties of a novel, conformationally restricted 2,3-dihydro-1,3,4-thiadiazole-containing angiotensin converting enzyme inhibitor which is preferentially eliminated by the biliary route in rats.
AID182319% Inhibition of angiotensin-I induced pressor response in normotensive rats after intravenous dosing of 0.015 umol/kg1988Journal of medicinal chemistry, Jun, Volume: 31, Issue:6
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.
AID182321% Inhibition of angiotensin-I induced pressor response in normotensive rats after intravenous dosing of 0.15 umol/kg1988Journal of medicinal chemistry, Jun, Volume: 31, Issue:6
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.
AID182330% Inhibition of angiotensin-I induced pressor response in normotensive rats after peroral dosing of 5 umol/kg1988Journal of medicinal chemistry, Jun, Volume: 31, Issue:6
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.
AID39628Compound was tested for inhibitory activity against Angiotensin I converting enzyme when administered intraperitoneally to anesthetized dogs1989Journal of medicinal chemistry, Jul, Volume: 32, Issue:7
Angiotensin converting enzyme inhibitors: spirapril and related compounds.
AID26306Logarithm of the ratio of anionic to unionized species at pH 7.41991Journal of medicinal chemistry, Jan, Volume: 34, Issue:1
Design, synthesis, and physicochemical properties of a novel, conformationally restricted 2,3-dihydro-1,3,4-thiadiazole-containing angiotensin converting enzyme inhibitor which is preferentially eliminated by the biliary route in rats.
AID182327% Inhibition of angiotensin-I induced pressor response in normotensive rats after peroral dosing of 1.5 umol/kg1988Journal of medicinal chemistry, Jun, Volume: 31, Issue:6
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.
AID182320% Inhibition of angiotensin-I induced pressor response in normotensive rats after intravenous dosing of 0.05 umol/kg1988Journal of medicinal chemistry, Jun, Volume: 31, Issue:6
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.
AID38465Compound tested in vivo for inhibition of angiotensin converting enzyme in rat1989Journal of medicinal chemistry, Jul, Volume: 32, Issue:7
Angiotensin converting enzyme inhibitors: spirapril and related compounds.
AID37962In vitro inhibitory activity against angiotensin I converting enzyme of rats.1988Journal of medicinal chemistry, Jun, Volume: 31, Issue:6
Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.
AID1345457Human Angiotensin-converting enzyme (M2: Angiotensin-converting (ACE and ACE2))1989Journal of medicinal chemistry, Jul, Volume: 32, Issue:7
Angiotensin converting enzyme inhibitors: spirapril and related compounds.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (20)

TimeframeStudies, This Drug (%)All Drugs %
pre-19906 (30.00)18.7374
1990's13 (65.00)18.2507
2000's1 (5.00)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials7 (35.00%)5.53%
Reviews1 (5.00%)6.00%
Case Studies1 (5.00%)4.05%
Observational0 (0.00%)0.25%
Other11 (55.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]