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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H26N2O5S2
Molecular Weight 438.5638
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SPIRAPRILAT

SMILES

C[C@@]([H])(C(=O)N1CC2(C[C@@]1([H])C(=O)O)SCCS2)N[C@@]([H])(CCc3ccccc3)C(=O)O

InChI

InChIKey=FMMDBLMCSDRUPA-BPUTZDHNSA-N
InChI=1S/C20H26N2O5S2/c1-13(21-15(18(24)25)8-7-14-5-3-2-4-6-14)17(23)22-12-20(28-9-10-29-20)11-16(22)19(26)27/h2-6,13,15-16,21H,7-12H2,1H3,(H,24,25)(H,26,27)/t13-,15-,16-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01348 | https://www.ncbi.nlm.nih.gov/pubmed/18154140 | https://www.ncbi.nlm.nih.gov/pubmed/15490771 | https://www.ncbi.nlm.nih.gov/pubmed/15752941

Spirapril (Renormax) is an ACE inhibitor antihypertensive drug used to treat hypertension. 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
67.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RENORMAX

Approved Use

Unknown

Launch Date

7.8865918E11
Primary
RENORMAX

Approved Use

Unknown

Launch Date

7.8865918E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
81.6 μg/L
6 mg 1 times / day multiple, oral
dose: 6 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SPIRAPRILAT plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
37.85 μg/L
6 mg 1 times / day multiple, oral
dose: 6 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SPIRAPRILAT plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
846.75 μg × h/L
6 mg 1 times / day multiple, oral
dose: 6 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SPIRAPRILAT plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
152.5 μg × h/L
6 mg 1 times / day multiple, oral
dose: 6 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SPIRAPRILAT plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.85 h
6 mg 1 times / day multiple, oral
dose: 6 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SPIRAPRILAT plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
24 mg 1 times / day steady, oral (max)
Recommended
Dose: 24 mg, 1 times / day
Route: oral
Route: steady
Dose: 24 mg, 1 times / day
Sources:
unhealthy, adult
n = 133
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 133
Sources:
Other AEs: Cough, Dizziness...
Other AEs:
Cough (3.8%)
Dizziness (5.3%)
Fatigue (6%)
Headache (9%)
Oedema (3%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Oedema 3%
24 mg 1 times / day steady, oral (max)
Recommended
Dose: 24 mg, 1 times / day
Route: oral
Route: steady
Dose: 24 mg, 1 times / day
Sources:
unhealthy, adult
n = 133
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 133
Sources:
Cough 3.8%
24 mg 1 times / day steady, oral (max)
Recommended
Dose: 24 mg, 1 times / day
Route: oral
Route: steady
Dose: 24 mg, 1 times / day
Sources:
unhealthy, adult
n = 133
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 133
Sources:
Dizziness 5.3%
24 mg 1 times / day steady, oral (max)
Recommended
Dose: 24 mg, 1 times / day
Route: oral
Route: steady
Dose: 24 mg, 1 times / day
Sources:
unhealthy, adult
n = 133
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 133
Sources:
Fatigue 6%
24 mg 1 times / day steady, oral (max)
Recommended
Dose: 24 mg, 1 times / day
Route: oral
Route: steady
Dose: 24 mg, 1 times / day
Sources:
unhealthy, adult
n = 133
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 133
Sources:
Headache 9%
24 mg 1 times / day steady, oral (max)
Recommended
Dose: 24 mg, 1 times / day
Route: oral
Route: steady
Dose: 24 mg, 1 times / day
Sources:
unhealthy, adult
n = 133
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: M+F
Population Size: 133
Sources:
PubMed

PubMed

TitleDatePubMed
Effect of long-term treatment with an angiotensin-converting enzyme inhibitor on the renin-angiotensin system in spontaneously hypertensive rats.
1991 Oct
Renal effects of angiotensin II in normotensive subjects on short-term cilazapril treatment.
1992
Alpha-adrenergic and angiotensin II pressor sensitivity in hypertensive patients treated with an angiotensin-converting enzyme inhibitor.
1992
Spirapril. A preliminary review of its pharmacology and therapeutic efficacy in the treatment of hypertension.
1995 May
Efficacy and safety of spirapril, a new ace-inhibitor, in elderly hypertensive patients.
1996
Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists.
1997 Sep
ACE-inhibitor therapy with spirapril increases nocturnal hypotensive episodes in elderly hypertensive patients.
2001 Dec
Effects of antihypertensive therapy on hemorheological profiles in female hypertensive patients with initially low or high whole blood viscosity.
2002
Antiproteinuric versus antihypertensive effects of high-dose ACE inhibitor therapy.
2002 Sep
Drug interaction of spirapril hydrochloride monohydrate and hydrochlorothiazide. A clinical study to compare the pharmacokinetics after administration of spirapril hydrochloride monohydrate tablets, hydrochlorothiazide tablets and fixed combination bi-layer tablets.
2003
Simultaneous determination of spirapril and spiraprilat in plasma by capillary gas chromatography-mass spectrometry.
2003
Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey.
2005 Jun 8
Thermodynamics of non-stoichiometric pharmaceutical hydrates.
2005 Oct 13
[Effect of spirapril on remodeling of the heart in patients with mild and moderate arterial hypertension].
2007
[A comparative analysis of normodipin and spirapril effects on intravascular activity of platelets in patients with metabolic syndrome].
2007
The Lipid lowering and Onset of Renal Disease (LORD) Trial: a randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease.
2008 Mar 18
Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited.
2008 Nov
Identification and determination of antihypertonics from the group of angiotensin-convertase inhibitors by densitometric method in comparition with HPLC method.
2010 Mar-Apr
Administration-time-dependent effects of spirapril on ambulatory blood pressure in uncomplicated essential hypertension.
2010 May
Patents

Sample Use Guides

The daily dose is 6 mg, the frequency of application is 1 time / day. After 4-6 weeks, in the absence of a satisfactory therapeutic effect, the dose can be increased.
Route of Administration: Oral
Pooled human liver microsomes were obtained from Pfizer Global Supply and the tested compounds were acquired from Pfizer Global Material Management. Each incubation contained tested compounds (Spirapril) (1 mkM), microsomes (0.25 lM protein), NADPH regenerating system (1 mM NADP+, 5 mM isocitric acid and 1 unit/ mL isocitric dehydrogenase), MgCl2 (1 mM) and potassium phosphate buffer (100 mM at pH 7.4). This mixture was incubated at 37 _C for 0, 5, 10, 20, 30 and 60 min before quenching with acetonitrile. Control incubations were prepared using the same procedure without adding the catalytic cofactor NADPH. Individual samples were then analyzed in a ‘trap-and-elute’ mode using LC/MS
Name Type Language
SPIRAPRILAT
INN   USAN  
INN   USAN  
Official Name English
SCH-33861
Code English
SPIRAPRILAT [INN]
Common Name English
SPIRAPRIL DIACID
MI  
Common Name English
SPIRAPRILAT [USAN]
Common Name English
SPIRAPRIL HYDROCHLORIDE MONOHYDRATE IMPURITY B [EP]
Common Name English
(8S)-7-((2S)-2-(((1S)-1-CARBOXY-3-PHENYLPROPYL)AMINO)PROPANOYL)-1,4-DITHIA-7-AZASPIRO(4.4)NONANE-8-CARBOXYLIC ACID
Systematic Name English
SPIRAPRIL DIACID [MI]
Common Name English
(2S)-3-((2S)-2-(((1S)-1-CARBOXY-3-PHENYL-PROPYL)AMINO)PROPANOYL)-6,9-DITHIA-3-AZASPIRO(4.4)NONANE-2-CARBOXYLIC ACID
Systematic Name English
SCH 33861
Code English
Classification Tree Code System Code
NCI_THESAURUS C247
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
Code System Code Type Description
EPA CompTox
83602-05-5
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
INN
6357
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
IUPHAR
6576
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
MESH
C076884
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
CAS
83602-05-5
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
ChEMBL
CHEMBL579
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
NCI_THESAURUS
C152419
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
PUBCHEM
3033702
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
MERCK INDEX
M10150
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY Merck Index
FDA UNII
QS56V5Y7EC
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY
EVMPD
SUB10621MIG
Created by admin on Sat Jun 26 13:24:45 UTC 2021 , Edited by admin on Sat Jun 26 13:24:45 UTC 2021
PRIMARY