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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H26N2O5S2
Molecular Weight 438.561
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SPIRAPRILAT

SMILES

C[C@H](N[C@@H](CCC1=CC=CC=C1)C(O)=O)C(=O)N2CC3(C[C@H]2C(O)=O)SCCS3

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

Molecular Formula C20H26N2O5S2
Molecular Weight 438.561
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Alpha-adrenergic and angiotensin II pressor sensitivity in hypertensive patients treated with an angiotensin-converting enzyme inhibitor.
1992
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
[Blood pressure control must be effective until the next tablet. Infarct is most frequent in the morning].
2002 Jan 24
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
[Effect of spirapril on remodeling of the heart in patients with mild and moderate arterial hypertension].
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
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
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:50:14 UTC 2023
Edited
by admin
on Fri Dec 15 15:50:14 UTC 2023
Record UNII
QS56V5Y7EC
Record Status Validated (UNII)
Record Version
  • Download
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
(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
SPIRAPRIL HYDROCHLORIDE MONOHYDRATE IMPURITY B [EP IMPURITY]
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 Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
Code System Code Type Description
SMS_ID
100000083804
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
EPA CompTox
DTXSID30232453
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
INN
6357
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
IUPHAR
6576
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
MESH
C076884
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
USAN
AA-32
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
CAS
83602-05-5
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
ChEMBL
CHEMBL579
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
NCI_THESAURUS
C152419
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
WIKIPEDIA
Spiraprilat
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
PUBCHEM
3033702
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
MERCK INDEX
m10150
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY Merck Index
FDA UNII
QS56V5Y7EC
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
EVMPD
SUB10621MIG
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
CHEBI
141522
Created by admin on Fri Dec 15 15:50:14 UTC 2023 , Edited by admin on Fri Dec 15 15:50:14 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY