SPIRAPRILAT

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 Search

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
Sources: https://www.drugs.com/international/spirapril.html
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Angiotensin-converting enzyme 97 Target ID: CHEMBL1808 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2544729	Inhibitor 8297		67.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.drugs.com/international/spirapril.html	Primary		Approved 8429	RENORMAX Approved Use Unknown Launch Date 1994
Metabolic syndrome 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18154140	Primary		Not Provided 504	RENORMAX Approved Use Unknown Launch Date 1994

C_max

Value	Dose	Co-administered	Analyte	Population
81.6 μg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/7601014/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/7601014/	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

Value	Dose	Co-administered	Analyte	Population
846.75 μg × h/L REVIEW https://pubmed.ncbi.nlm.nih.gov/7601014/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/7601014/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.85 h REVIEW https://pubmed.ncbi.nlm.nih.gov/7601014/	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/7601014/	unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: https://pubmed.ncbi.nlm.nih.gov/7601014/	Other AEs: Cough, Dizziness... Other AEs: Cough (3.8%) Dizziness (5.3%) Fatigue (6%) Headache (9%) Oedema (3%) Sources: https://pubmed.ncbi.nlm.nih.gov/7601014/

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/7601014/	unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: https://pubmed.ncbi.nlm.nih.gov/7601014/
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: https://pubmed.ncbi.nlm.nih.gov/7601014/	unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: https://pubmed.ncbi.nlm.nih.gov/7601014/
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: https://pubmed.ncbi.nlm.nih.gov/7601014/	unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: https://pubmed.ncbi.nlm.nih.gov/7601014/
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: https://pubmed.ncbi.nlm.nih.gov/7601014/	unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: https://pubmed.ncbi.nlm.nih.gov/7601014/
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: https://pubmed.ncbi.nlm.nih.gov/7601014/	unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: https://pubmed.ncbi.nlm.nih.gov/7601014/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:141522	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:141522
ZINC	ZINC000004217460	http://zinc15.docking.org/substances/ZINC000004217460

PubMed

Title	Date	PubMed
Effect of long-term treatment with an angiotensin-converting enzyme inhibitor on the renin-angiotensin system in spontaneously hypertensive rats.	1991 Oct	1764812
Renal effects of angiotensin II in normotensive subjects on short-term cilazapril treatment.	1992	1382161
Alpha-adrenergic and angiotensin II pressor sensitivity in hypertensive patients treated with an angiotensin-converting enzyme inhibitor.	1992	1382157
Spirapril. A preliminary review of its pharmacology and therapeutic efficacy in the treatment of hypertension.	1995 May	7601014
Efficacy and safety of spirapril, a new ace-inhibitor, in elderly hypertensive patients.	1996	8737752
Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists.	1997 Sep	9300315
ACE-inhibitor therapy with spirapril increases nocturnal hypotensive episodes in elderly hypertensive patients.	2001 Dec	11773991
A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension.	2001 May	11393383
[ACE inhibitor. Effective blood pressure control around the clock].	2001 Sep 6	11584537
[Effect of angiotensin converting enzyme inhibitor spirapril on dimensions of experimental myocardial infarction, development of ischemic tachyarrhythmias, and ischemic adaptation of the heart].	2002	12494232
Effects of antihypertensive therapy on hemorheological profiles in female hypertensive patients with initially low or high whole blood viscosity.	2002	12082261
Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update.	2002	11929321
[Influence of ACE inhibitor spirapril on left ventricular hypertrophy].	2002 Dec 5	12613273
[Blood pressure control must be effective until the next tablet. Infarct is most frequent in the morning].	2002 Jan 24	11862799
[Hypertensive patient with diabetes. "Blood pressure cosmetics" are not enough here].	2002 Jun 13	12138889
[Open trial using ACE inhibitor. Left ventricular hypertrophy diminishes].	2002 Nov 28	12532545
Antiproteinuric versus antihypertensive effects of high-dose ACE inhibitor therapy.	2002 Sep	12200795
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	12872612
Simultaneous determination of spirapril and spiraprilat in plasma by capillary gas chromatography-mass spectrometry.	2003	12854357
[Blood pressure lowering by the ACE-inhibitor spirapril. "24-hour efficacy of real once daily application of spirapril (HERAS Study)"].	2003 Oct 2	14603605
[Blood pressure lowering by the ACE-inhibitor spirapril. "24-hour efficacy of real once daily application of spirapril (HERAS study)"].	2003 Oct 9	15490771
Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey.	2005 Jun 8	15943871
Thermodynamics of non-stoichiometric pharmaceutical hydrates.	2005 Oct 13	16139971
Central angiotensin II controls alcohol consumption via its AT1 receptor.	2005 Sep	16126915
[Rational approach to selection of antihypertensive therapy in persons with metabolic syndrome: efficacy of monotherapy with spirapril and its combination with retard form of nifedipine].	2006	17047619
[Clinical application of spirapril in patients with arterial hypertension combined with chronic obstructive pulmonary disease].	2006	17047595
[Quadropril (spirapril) in the treatment of isolated systolic hypertension in patients with type 2 diabetes mellitus].	2006	16883265
[Advantages of long-term controlled stepwise therapy of arterial hypertension with the use of angiotensin converting enzyme inhibitor spirapril].	2006	16710253
[Comparative efficacy and safety of contemporary Angiotensin converting enzyme inhibitors moexipril and spirapril in women with postmenopausal metabolic syndrome].	2006	16474309
[Effect of spirapril on remodeling of the heart in patients with mild and moderate arterial hypertension].	2007	18260839
[A comparative analysis of normodipin and spirapril effects on intravascular activity of platelets in patients with metabolic syndrome].	2007	18154140
Plasticity and impact of the central renin-angiotensin system during development of ethanol dependence.	2007 Oct	17823780
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	18366658
Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited.	2008 Nov	18713951
Identification and determination of antihypertonics from the group of angiotensin-convertase inhibitors by densitometric method in comparition with HPLC method.	2010 Mar-Apr	20369790
Administration-time-dependent effects of spirapril on ambulatory blood pressure in uncomplicated essential hypertension.	2010 May	20524801

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 GMT 2023` Edited by `admin` on `Fri Dec 15 15:50:14 GMT 2023`
Record UNII	QS56V5Y7EC
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SPIRAPRILAT

Official Name

English

SCH-33861

Code

English

spiraprilat [INN]

Common Name

English

SPIRAPRIL DIACID

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