TRANDOLAPRIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H34N2O5
Molecular Weight	430.5372
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@H](N(C(=O)[C@H](C)N[C@@H](CCC3=CC=CC=C3)C(=O)OCC)[C@@]1([H])CCCC2)C(O)=O

InChI

InChIKey=VXFJYXUZANRPDJ-WTNASJBWSA-N

InChI=1S/C24H34N2O5/c1-3-31-24(30)19(14-13-17-9-5-4-6-10-17)25-16(2)22(27)26-20-12-8-7-11-18(20)15-21(26)23(28)29/h4-6,9-10,16,18-21,25H,3,7-8,11-15H2,1-2H3,(H,28,29)/t16-,18+,19-,20-,21-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C24H34N2O5
Molecular Weight	430.5372
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB00519
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020528s024lbl.pdf

Trandolapril is a non-sulhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to its biologically active diacid form, trandolaprilat, in the liver. Trandolaprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Trandolapril may be used to treat mild to moderate hypertension, to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction, as an adjunct treatment for congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy. Trandolapril is marketed by Abbott Laboratories under the brand name Mavik.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Angiotensin-converting enzyme 97 Target ID: CHEMBL1808 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020528s024lbl.pdf \| http://www.drugbank.ca/drugs/DB00519	Inhibitor 8297		15.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020528s024lbl.pdf	Primary		Approved 8429	MAVIK Approved Use Hypertension MAVIK is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medication such as hydrochlorothiazide. Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction MAVIK is indicated in stable patients who have evidence of left-ventricular systolic dysfunction (identified by wall motion abnormalities) or who are symptomatic from congestive heart failure within the first few days after sustaining acute myocardial infarction. Launch Date 1996
Heart failure post myocardial infarction 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020528s024lbl.pdf	Primary		Approved 8429	MAVIK Approved Use Hypertension MAVIK is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medication such as hydrochlorothiazide. Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction MAVIK is indicated in stable patients who have evidence of left-ventricular systolic dysfunction (identified by wall motion abnormalities) or who are symptomatic from congestive heart failure within the first few days after sustaining acute myocardial infarction. Launch Date 1996

C_max

Value	Dose	Analyte	Population
9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.99 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.3 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.2 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
101 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
19.1 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.8 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.2 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
115 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	unhealthy, 55 n = 151 Health Status: unhealthy Condition: hypertension Age Group: 55 Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	Disc. AE: Diarrhea, Dizziness... AEs leading to discontinuation/dose reduction: Diarrhea Dizziness Elevated liver enzymes Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/

AEs

AE	Significance	Dose	Population
Diarrhea	Disc. AE	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	unhealthy, 55 n = 151 Health Status: unhealthy Condition: hypertension Age Group: 55 Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/
Dizziness	Disc. AE	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	unhealthy, 55 n = 151 Health Status: unhealthy Condition: hypertension Age Group: 55 Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/
Elevated liver enzymes	Disc. AE	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	unhealthy, 55 n = 151 Health Status: unhealthy Condition: hypertension Age Group: 55 Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CES1 22 CES2 28

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CES2 28	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24141856/	no	TRANDOLAPRIL 3
CES1 22	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24141856/	yes [Km 1721 uM]	TRANDOLAPRIL 3

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1477	http://www.3bsc.com/index/pro_info.php?id=55193
Alfa Chemistry	AP87679718	https://reagents.alfa-chemistry.com/product/trandolapril-related-compound-e-cas-87679-71-8-17686.html
Alfa Chemistry	83601-86-9	https://www.alfa-chemistry.com/cas_83601-86-9.htm
BLD Pharm	BD154453	http://www.bldpharm.com/products/87679-71-8.html
ChemMol	49422350	http://www.chemmol.com/chemmol/49422350.html
Clearsynth	CS-O-08347	https://www.clearsynth.com/en/CSO08347.html
DC Chemicals	DC32672	http://www.dcchemicals.com//product_show-Trandolaprilat.html
Excenen	EX-A4862	https://www.excenen.com/searchresultlist.php?id=EX-A4862
Glentham Life Sciences	GP7119	http://www.glentham.com/products/product/GP7119/
MuseChem	R044833	https://www.musechem.com/product/R044833.html
OChem	21859	http://www.ocheminc.com/index.php?act=psearch&pid=679T718
Smolecule	S545706	http://www.smolecule.com/products/s545706
THE BioTek	bt-286404	https://www.thebiotek.com/product/inhibitors/bt-286404
eNovation Chemicals	D591705	https://www.enovationchem.com/ProductDetails.asp?ProductID=D591705
iChemical	EBD21706	http://www.ichemical.com/products/87679-71-8.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation.	1999 Jul 3	10406358
Early neurohormonal effects of trandolapril in patients with left ventricular dysfunction and a recent acute myocardial infarction: a double-blind, randomized, placebo-controlled multicentre study.	2001 Jan	11163738
Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in essential hypertensive patients with left ventricular hypertrophy.	2001 Jan-Feb	11277342
What are 'tissue ACE inhibitors,' and should they be used instead of other ACE inhibitors?	2001 Mar	11263844
Characteristics of patients with coronary artery disease and hypertension: a report from INVEST.	2001 Nov	11712775
Beneficial effect of trandolapril on the lifespan of a severe hypertensive model.	2001 Sep	11675951
High-dose verapamil + trandolapril-induced thrombotic microangiopathy.	2002	12611489
[Clinical sequelae of tissue angiotensin converting enzyme inhibition: practicability of use in ischemic heart disease].	2002	12494137
Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension.	2002	12421112
[Treatment of hypertension in diabetics with trandolapril, an angiotensin converting enzyme inhibitor--a multicenter study].	2002 Aug	12425199
Beneficial effects of trandolapril in uninephrectomized spontaneously hypertensive rats: role of cyclooxygenase pathway.	2002 Aug	12420798
Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project.	2002 Aug	12149667
Using ACE inhibitors appropriately.	2002 Aug 1	12182524
Time-effect profile of antihypertensive agents assessed with trough/peak ratio, smoothness index and dose omission: an ambulatory blood pressure monitoring study with trandolapril vs. quinapril.	2002 Dec	12685514
Metabolic effects of combined antihypertensive treatment in patients with essential hypertension.	2002 Dec	12451325
Impact of age and sex on sudden cardiovascular death following myocardial infarction.	2002 Dec	12433881
Subcellular and molecular mechanisms of the effects of cardiac glycosides and angiotensin-converting enzyme inhibitors on contractile function and energy conversion in myocardial myofibrils under normal conditions and during acute cardiac insufficiency.	2002 Jan	12170313
Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression.	2002 Jan 16	11788231
Trandolapril reduces infarction area after middle cerebral artery occlusion in rats.	2002 Jul	12358145
Severe angioedema induced by angiotensin converting enzyme inhibitors: role of precipitating factors.	2002 Jun	12126067
Relative long-term effects of spironolactone in conjunction with an angiotensin-converting enzyme inhibitor on left ventricular mass and diastolic function in patients with essential hypertension.	2002 Nov	12484506
[The effect of angiotensin-converting enzyme inhibitors on the progression of chronic renal failure].	2002 Nov 9	12467154
Angiotensin-converting enzyme inhibition and endothelin antagonism for endothelial dysfunction in heart failure: mono-or combination therapy.	2002 Oct	12352322
The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT): design and baseline characteristics.	2003 Aug	12865039
Combination treatment with an ET(A)-receptor blocker and an ACE inhibitor is not superior to the respective monotherapies in attenuating chronic transplant vasculopathy in different aorta allotransplantation rat models.	2003 Jan	12480961
Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial.	2003 Jan 11	12531578
Trandolapril: a newer angiotensin-converting enzyme inhibitor.	2003 Mar	12852701
Differing anti-proteinuric action of candesartan and losartan in chronic renal disease.	2003 Nov	14714578
Submaximal dose of trandolapril in the COOPERATE trial?	2003 Nov	14531832
Angiotensin-converting enzyme inhibitor trandolapril does not affect C-reactive protein levels in myocardial infarction patients.	2003 Oct 14	14557351
[Induction of heat shock protein 70 in failing heart].	2004 Feb	14745126
ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes.	2004 Feb	14727024
[Preventive therapy with ACE inhibitors for coronary patients].	2004 Feb 29	15077477
Effects of bedtime vs. morning administration of the long-acting lipophilic angiotensin-converting enzyme inhibitor trandolapril on morning blood pressure in hypertensive patients.	2004 Jan	15055251
Significant target organs for hypertension and cardiac hypertrophy by angiotensin-converting enzyme inhibitors.	2004 Mar	15080380
[Effects of angiotensin II receptor blockers, angiotensin converting enzyme inhibitors, 3-hydroxy-3-methyl glutaryl (HMG) CoA reductase inhibitors, amlodipine and epalrestat on cultured basilar artery smooth muscle cell proliferation].	2004 Mar	15049134
Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism.	2004 Mar 1	14984722
[Diagnosis of and therapy for renal hypertension].	2004 Mar 10	15052808
[Therapeutic strategy for patients with stable-stage chronic kidney failure].	2004 Mar 10	15052806
Pharmacological treatment and prevention of heart failure in the diabetic patient.	2004 Winter	15029109

Patents

Sample Use Guides

In Vivo Use Guide

The recommended initial dosage of MAVIK (Trandolapril) for patients not receiving a diuretic is 1 mg once daily in non-black patients and 2 mg in black patients.

Route of Administration: Oral

In Vitro Use Guide

Trandolapril at 10(-7) mol/l, significantly increased 11beta-HSD2 activity after pretreatment for 16 or 24 h of the human epithelial colon cell line SW-620

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:43:47 GMT 2023` Edited by `admin` on `Fri Dec 15 15:43:47 GMT 2023`
Record UNII	1T0N3G9CRC
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRANDOLAPRIL

Official Name

English

TRANDOLAPRIL [USP-RS]

Common Name

English

TRANDOLAPRIL [VANDF]

Common Name

English

TRANDOLAPRIL [JAN]

Common Name

English

1H-INDOLE-2-CARBOXYLIC ACID, OCTAHYDRO N-((2S)-1-ETHOXY-1-OXO-4-PHENYLBUTAN-2-YL)-1-ALANYL (2S,3AR,7AS)

Common Name

English

TRANDOLAPRIL [EP MONOGRAPH]

Common Name

English

TRANDOLAPRIL [USP MONOGRAPH]

Common Name

English

TRANDOLAPRIL [MI]

Common Name

English

(2S,3aR,7aS)-1-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester

Common Name

English

NSC-758939

Code

English

TRANDOLAPRIL [ORANGE BOOK]

Common Name

English

TARKA COMPONENT TRANDOLAPRIL

Common Name

English

TRANDOLAPRIL COMPONENT OF TARKA

Common Name

English

TRANDOLAPRIL [MART.]

Common Name

English

RU 44570

Code

English

MAVIK

Brand Name

English

Trandolapril [WHO-DD]

Common Name

English

trandolapril [INN]

Common Name

English

RU-44570

Code

English

Classification Tree Code System Code

WHO-VATC

QC09AA10