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Enalapril maleate

CAS：76095-16-4
MW:492.525
MF：C24H32N2O9

Enalapril maleate, with the chemical formula C20H28N2O5 and CAS registry number 76095-16-4, is a compound used primarily as an antihypertensive medication. It belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors. Enalapril maleate works by inhibiting the action of ACE, an enzyme involved in the production of a hormone called angiotensin II, which constricts blood vessels and increases blood pressure. By blocking the effects of angiotensin II, enalapril maleate helps to relax and widen blood vessels, reducing blood pressure and improving blood flow. This medication is commonly prescribed for the treatment of high blood pressure, heart failure, and certain kidney conditions. Enalapril maleate is typically taken orally in tablet form and may be used alone or in combination with other medications. It is important to follow the prescribed dosage and consult a healthcare professional for personalized advice and guidance.

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Names and ldentifier
Properties
Use and Manufacturing
Safety and Handling
Msds
Other Information
Computational chemical data
Related Questions
Realated Product Infomation

1. Names and Identifiers

1.1 Name: Enalapril maleate

1.2 Synonyms: (2S)-1-[(2S)-2-{[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino}propanoyl]pyrrolidin-2-carbonsäure--(2Z)-but-2-endisäure(1:1); (2S)-1-[(2S)-2-{[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino}propanoyl]pyrrolidine-2-carboxylic acid (2Z)-but-2-enedioate; (S)-1-((S)-2-((S)-1-ETHOXY-1-OXO-4-PHENYLBUTAN-2-YLAMINO)PROPANOYL)PYRROLIDINE-2-CARBOXYLIC ACID MALEATE; 1-(n-(1-(ethoxycarbonyl)-3-phenylpropyl)-l-alanyl)-l-prolin(s)-l-prolin(z)-2-bu; 1-[n-[1-(ethoxycarbonyl)-3-phenylpropyl]-l-alanyl]-l-prolin(s)-l-prolin(z)-2-but; Acapril; Acetensil; acide (2S)-1-[(2S)-2-{[(1S)-1-(éthoxycarbonyl)-3-phénylpropyl]amino}propanoyl]pyrrolidine-2-carboxylique - acide (2Z)-but-2-ènedioïque (1:1); EINECS 278-375-7; Enalapril; Enalapril maleate BP2000/USP25; Enalapril maleate salt; Enalapril Maleate　USP24,25,EP2000; ENALAPRIL MALLATE; L-proline, N-(1S)-1-(ethoxycarbonyl)-3-phenylpropyl-L-alanyl-, (2Z)-2-butenedioate (1:1); L-Proline, N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]alanyl-, (2E)-2-butenedioate (1:1); L-Proline, N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-, (2Z)-2-butenedioate (1:1); MFCD00133304; MK 421 {Maleate}; MK 421 maleate; mk421maleate; n-((s)-1-ethoxycarbonyl-3-phenylpropyl)-l-alanyl-l-proline maleate; N-(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl-L-alanyl-L-proline (2Z)-but-2-enedioate; N-[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline (2Z)-2-butenedioate; N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline (2Z)-but-2-enedioate; N-[(2S)-1-Ethoxy-1-oxo-4-phenyl-2-butanyl]alanyl-L-proline (2E)-2-butenedioate (1:1); N-[(2S)-1-Ethoxy-1-oxo-4-phenyl-2-butanyl]-L-alanyl-L-proline (2Z)-2-butenedioate (1:1); N-[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]-L-alanyl-L-proline (2Z)-but-2-enedioate (1:1); Renivace; Renivace (TN); VASOTEC;

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1.3 CAS No.: 76095-16-4

1.4 CID: 5388961

1.5 EINECS: 278-375-7

1.6 Molecular Formula: C24H32N2O9

1.7 Inchi: InChI=1S/C20H28N2O5.C4H4O4/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25;5-3(6)1-2-4(7)8/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25);1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-,16-,17-;/m0./s1

1.8 InChkey: OYFJQPXVCSSHAI-QFPUQLAESA-N

1.9 Canonical Smiles: CCOC(=O)C(CCC1=CC=CC=C1)NC(C)C(=O)N2CCCC2C(=O)O.C(=CC(=O)O)C(=O)O

1.10 Isomers Smiles: CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)O.C(=C\C(=O)O)\C(=O)O

2. Properties

2.1 Solubility: methanol: ≥50?mg/mL, clear, colorless to yellow

2.2 Λmax: 208nm(MeOH)(lit.)

2.3 AnalyticLaboratory Methods: Analyte: enalapril maleate;; matrix: chemical purity; procedure: liquid chromatography with detection at 215 nm and comparison to standards

2.4 Appearance: White to Off-White Crystalline Powder

2.5 Storage: -20°C Freezer

2.6 Chemical Properties: White to Off-White Crystalline Powder

2.7 Color/Form: Powder

2.8 PH: pH (1% water) 2.6

2.9 pKa: pKa1 3.0; pKa2 (25°) 5.4

2.10 Water Solubility: methanol: ≥50?mg/mL, clear, colorless to yellow

2.11 Spectral Properties: Specific optical rotation: -42.2 deg at 25 deg C/D (concentration by volume = 1 g in 100 ml methanol)

2.12 Stability: Commercially available enalaprilat; injection should be stored at a temperature less than 30 deg C. Following dilution of enalaprilat; injection in 5% dextrose, 0.9% sodium chloride;, 5% dextrose and 0.9% sodium chloride;, 5% dextrose in lactated Ringer's, or Isolyte;(R) E, solutions of the drug are stable for 24 hrs at room temperature. /Enalaprilat;/

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2.13 StorageTemp: 2-8°C

3. Use and Manufacturing

3.1 Definition: ChEBI: The maleic acid salt of enalapril. It contains one molecule of maleic acid for each molecule of enalapril. Following oral administration, the ethyl ester group of enalapril is hydrolysed to afford the corresponding carboxylic acid, enalaprilat, an angiotenin-converting enzyme (ACE) inhibitor. Enalapril is thus a prodrug for enalaprilat (which, unlike enalapril, is not absorbed by mouth), and its maleate is used in the treatment of hypertension and heart failure, for reduction of proteinuria and renal diseas in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients.

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3.2 Description

Enalapril maleate, with the chemical formula C20H28N2O5.C4H4O4, has the CAS number 76095-16-4. It appears as a white to off-white, crystalline powder with a slight characteristic odor. The basic structure of enalapril maleate consists of a carboxyl group, an ethyl ester group, and a tetrahydrofuran ring. This compound is soluble in water and ethanol. Enalapril maleate is a medication used to treat high blood pressure and heart failure. It works by inhibiting the enzyme that converts angiotensin I to angiotensin II, thereby reducing blood pressure and improving cardiac function. Enalapril maleate is generally well-tolerated, but may cause side effects such as dizziness, cough, and low blood pressure. It is important to follow the prescribed dosage and consult a healthcare professional for proper use and monitoring.

Applicable Fields

Hypertension: Enalapril maleate is primarily used for the treatment of hypertension, or high blood pressure. Its mechanism of action involves inhibiting the enzyme responsible for the production of angiotensin II, a hormone that constricts blood vessels. By reducing the levels of angiotensin II, enalapril maleate helps relax and widen the blood vessels, thereby lowering blood pressure.

Heart Failure: Enalapril maleate is also indicated for the treatment of heart failure. In heart failure, the heart is unable to pump blood effectively, leading to symptoms such as shortness of breath and fatigue. Enalapril maleate helps improve cardiac function by reducing the workload on the heart and improving blood flow.

Storage

Conditions: Store in a cool and dry place.

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3.3 General Description: Enalapril maleate, 1-[N[(S)-1-carboxy-3-phenylpropyl]-L-alanyl]-L-proline 1 -ethyl estermaleate (Vasotec), is a long-acting ACE inhibitor. It requiresactivation by hydrolysis of its ethyl ester to form thediacid enalaprilat. Enalapril is devoid of the side effects ofrash and loss of taste seen with captopril. These side effectsare similar to those of the mercapto-containing drugpenicillamine. The absence of the thiol group in enalaprilmaleate may free it from these side effects. The half-life is11 hours.

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3.4 GHS Classification: Signal: Danger
GHS Hazard Statements
Aggregated GHS information provided by 136 companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria by 2 of 136 companies. For more detailed information, please visit ECHA C&L website

Of the 20 notification(s) provided by 134 of 136 companies with hazard statement code(s):

H302 (27.61%): Harmful if swallowed [Warning Acute toxicity, oral]
H318 (47.76%): Causes serious eye damage [Danger Serious eye damage/eye irritation]
H319 (32.84%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H360 (31.34%): May damage fertility or the unborn child [Danger Reproductive toxicity]
H361 (37.31%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]
H362 (16.42%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]
H373 (26.87%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

Precautionary Statement Codes
P201, P202, P260, P263, P264, P270, P280, P281, P301+P312, P305+P351+P338, P308+P313, P310, P314, P330, P337+P313, P405, and P501

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3.5 Usage: sunscreen

4. Safety and Handling

4.1 Exposure Standards and Regulations: The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl enalapril maleate and enalprilat, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /Enalapril maleate and enalaprilat/
Enalapril tablets. ... Indications for use. Treatment of mild, moderate, and severe (modified New York Heart Association Class II, III, IV) heart failure in dogs. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian.
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392). [

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4.2 DisposalMethods: SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

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4.3 Formulations/Preparations: Oral Tablets: 5 mg with Hydrochlorothiazide 12.5 mg, Vaseretic, Biovail; 10 mg with Hydrochlorothiazide 25 mg, Vaseretic, Biovail. /Enalapril Maleate Combinations/
Parenteral Injection, for IV use only equivalent to 1.25 mg of anhydrous enalaprilat per ml: Vasotec I.V. (with benzyl alcohol 0.9%), Biovail; Enalaprilat Injection, Abbott, Baxter, Bedford, Faulding. /Enalaprilat/
Oral Tablets, 2.5, Vasotec (scored), Biovail; 5 mg, Vasotec (scored), Biovail; 10 mg, Vasotec, Biovail; 20 mg, Vasotec, Biovail. /Enalapril maleate/
Enalapril maleate (Vasotec)
Enalaprilat (Vasotec injection). /Enalaprilat/
Enalapril maleate and hydrochlorothiazide tablets: 5 mg of enalapril maleate and 12.5 mg of hydrochlorothiazide, 10 mg of enalapril maleate and 25 mg of hydrochlorothiazide.
Enalapril maleate and diltiazem malate extended-release tablets (Withdrawn from US market in December 1999).
Enalapril maleate and felodipine tablets: 5 mg enalapril and 2.5 mg felodipine extended release; 5 mg enalapril and 5 mg felodipine extended release.
Amprace, Bitensil, Cardiovet, Enacard, Enaloc, Enapren, Glioten, Hipoartel, Innovace, Lotrial, Naprilene, Olivin, Pres, Renitec, Reniten, Renivace, Vasotec, Xanef
Vasotec IV /Enalaprilat/

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4.4 Safety: Moderately toxic by ingestion, subcutaneous, and intravenous routes. Human systemic effects by ingestion: blood pressure depression, dermatitis, cough. An experimental teratogen. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx.

4.5 Specification

The Enalapril maleate with the cas number 76095-16-4, is also called (Z)-but-2-enedioic acid; (2S)-1-[(2S)-2-[[(2R)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]pyrrolidine-2-carboxylic acid. It's system Name are (1) (S)-1-(N-(1-(Ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline maleate (1:1) ; (2) L-Proline, 1-(N-(1-(ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-, (S)-, (Z)-2-butenedioate (1:1) ; (3) L-Proline, N-((1S)-1-(ethoxycarbonyl)-3-phenylpropyl)-L-alanyl-, (2Z)-2-butenedioate (1:1). It belongs to the following product categories: (1)All Inhibitors; (2)Inhibitors; (3)Intermediates & Fine Chemicals; (4)Pharmaceuticals; (5)Enalapril and so on.

Physical properties about Enalapril maleate are: (1)ACD/LogP: 2.42 ; (2)# of Rule of 5 Violations: 1 ; (3)#H bond acceptors: 11 ; (4)#H bond donors: 4 ; (5)#Freely Rotating Bonds: 12 ; (6)Polar Surface Area: 170.54??² ; (7)Flash Point: 416.7 °C ; (8)Enthalpy of Vaporization: 116.92 kJ/mol ; (9)Boiling Point: 765.3 °C at 760 mmHg ; (10)Vapour Pressure: 1.25E-24 mmHg at 25°C

Uses of Enalapril maleate: This drug is used to treat high blood pressure (hypertension) in adults and children. It belongs to a group of medications called ACE inhibitors which can relax blood vessels, causing them to widen, lowering high blood pressure helps prevent strokes, heart attacks and kidney problems. This medication is also used with other drugs (e.g., "water pills"/diuretics, digoxin) to treat congestive heart failure. Besides, this medication may also be used to help protect the kidneys from damage due to diabetes.

When you are using this chemical, please be cautious about it as the following: It is quite irritating to eyes, respiratory system and skin. When you are using this chemical, you should better wear suitable protective clothing and gloves to avoid contact with skin and eyes. In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.

You can still convert the following datas into molecular structure :
(1).SMILES: O=C(O)[C@@H]2CCCN2C(=O)[C@H](C)NC(CCc1ccccc1)C(=O)OCC.OC(=O)/C=C\C(O)=O
(2).InChI:InChI=1/C20H28N2O5.C4H4O4/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25;5-3(6)1-2-4(7)8/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25);1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-,16?,17-;/m0./s1

Toxic information of Enalapril maleate can be showed as follows:

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
man	TDLo	oral	71ug/kg (0.071mg/kg)	VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION	British Medical Journal. Vol. 291, Pg. 1309, 1985.
man	TDLo	oral	143ug/kg (0.143mg/kg)	SKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE"	British Medical Journal. Vol. 294, Pg. 91, 1987.
man	TDLo	oral	357ug/kg/3D-I (0.357mg/kg)	LUNGS, THORAX, OR RESPIRATION: ACUTE PULMONARY EDEMA	American Journal of Emergency Medicine. Vol. 8, Pg. 124, 1990.
mouse	LD50	intravenous	859mg/kg (859mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION BEHAVIORAL: ATAXIA	Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 13, Pg. 413, 1985.
mouse	LD50	oral	3507mg/kg (3507mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION BEHAVIORAL: ATAXIA	Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 13, Pg. 413, 1985.
mouse	LD50	subcutaneous	1160mg/kg (1160mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD BEHAVIORAL: ATAXIA LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 13, Pg. 413, 1985.
rat	LD50	intravenous	849mg/kg (849mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION BEHAVIORAL: ATAXIA	Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 13, Pg. 413, 1985.
rat	LD50	oral	2973mg/kg (2973mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION BEHAVIORAL: ATAXIA	Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 13, Pg. 413, 1985.
rat	LD50	subcutaneous	1418mg/kg (1418mg/kg)	BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD BEHAVIORAL: ATAXIA LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 13, Pg. 413, 1985.
women	TDLo	oral	400ug/kg/2D-I (0.4mg/kg)	SKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE"	British Medical Journal. Vol. 294, Pg. 91, 1987.
women	TDLo	oral	2800ug/kg/4W- (2.8mg/kg)	KIDNEY, URETER, AND BLADDER: RENAL FUNCTION TESTS DEPRESSED KIDNEY, URETER, AND BLADDER: OTHER CHANGES IN URINE COMPOSITION	British Medical Journal. Vol. 291, Pg. 450, 1985.
women	TDLo	oral	4mg/kg/10D-I (4mg/kg)	LIVER: "HEPATITIS (HEPATOCELLULAR NECROSIS), ZONAL" LIVER: LIVER FUNCTION TESTS IMPAIRED	Annals of Pharmacotherpy. Vol. 27, Pg. 1405, 1993.
women	TDLo	oral	5600ug/kg/4W- (5.6mg/kg)	SENSE ORGANS AND SPECIAL SENSES: OTHER CHANGES: OLFACTION	Lancet. Vol. 2, Pg. 1395, 1986.
women	TDLo	oral	39500ug/kg/56 (39.5mg/kg)	LUNGS, THORAX, OR RESPIRATION: ACUTE PULMONARY EDEMA LUNGS, THORAX, OR RESPIRATION: DYSPNEA LUNGS, THORAX, OR RESPIRATION: CYANOSIS	Journal of Family Practice. Vol. 34, Pg. 201, 1992.

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4.6 Toxicity

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TW3666000

CAS REGISTRY NUMBER :: 76095-16-4

LAST UPDATED :: 199709

DATA ITEMS CITED :: 28

MOLECULAR FORMULA :: C20-H28-N2-O5.C4-H4-O4

MOLECULAR WEIGHT :: 492.58

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 4 mg/kg/10D-I

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), zonal Liver - liver function tests impaired

REFERENCE :: APHRER Annals of Pharmacotherpy. (Harvey Whitney Books Co., POB 42696, Cincinnati, OH 45242) V. 26- 1992- Volume(issue)/page/year: 27,1405,1993

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 400 ug/kg/2D-I

TOXIC EFFECTS :: Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 294,91,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 357 ug/kg/3D-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema

REFERENCE :: AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 8,124,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 39500 ug/kg/56W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis

REFERENCE :: JFAPDE Journal of Family Practice. (Appleton and Lange, East Norwalk, CT) V.1- 1974- Volume(issue)/page/year: 34,201,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 143 ug/kg

TOXIC EFFECTS :: Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 294,91,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 2800 ug/kg/4W-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - renal function tests depressed Kidney, Ureter, Bladder - other changes in urine composition

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 291,450,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 71 ug/kg

TOXIC EFFECTS :: Vascular - BP lowering not characterized in autonomic section

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 291,1309,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 5600 ug/kg/4W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified

REFERENCE :: LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 2,1395,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2973 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,413,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1418 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,413,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 849 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,413,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3507 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,413,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1160 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,413,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 859 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,413,1985 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 900 mg/kg/30D-C

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - weight loss or decreased weight gain Nutritional and Gross Metabolic - changes in potassium

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,425,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 8190 mg/kg/13W-C

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes in urine composition Blood - leukopenia Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,425,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 600 mg/kg/4W-C

TOXIC EFFECTS :: Blood - normocytic anemia Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - death

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,467,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 8190 mg/kg/13W-C

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Related to Chronic Data - death

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,467,1985 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6800 ug/kg

SEX/DURATION :: female 32-34 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

REFERENCE :: AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 108,215,1988

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 95200 ug/kg

SEX/DURATION :: female 1-34 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 162,187,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 95200 ug/kg

SEX/DURATION :: female 1-34 week(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Effects on Newborn - Apgar score (human only)

REFERENCE :: AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 162,187,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 100 mg/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970- Volume(issue)/page/year: 77,347,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 144 mg/kg

SEX/DURATION :: female 6-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,519,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 100 mg/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - urogenital system

REFERENCE :: RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970- Volume(issue)/page/year: 77,347,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2520 mg/kg

SEX/DURATION :: female 15-22 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 14,43,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 280 mg/kg

SEX/DURATION :: female 15-22 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral Reproductive - Effects on Newborn - delayed effects

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 14,43,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 39 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 14,461,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 70 mg/kg

SEX/DURATION :: female 14-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 14,461,1990

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5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Serious eye damage, Category 1

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Danger
Hazard statement(s)	H318 Causes serious eye damage
Precautionary statement(s)
Prevention	P280 Wear protective gloves/protective clothing/eye protection/face protection.
Response	P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P310 Immediately call a POISON CENTER/doctor/\u2026
Storage	none
Disposal	none

2.3 Other hazards which do not result in classification

none

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6. Synthesis Route

76095-16-4Total: 10 Synthesis Route

2812-46-6 63 Suppliers

76095-16-4 396 Suppliers

80828-26-8 12 Suppliers

76095-16-4 396 Suppliers

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7. Precursor and Product

precursor:

147-85-3

108428-39-3

80828-38-2

82009-36-7

82717-96-2

2812-46-6

75847-73-3

406213-94-3

80828-26-8

103377-40-8

110-16-7

product:

256510-64-2

76420-72-9

8. Computed Properties

Molecular Weight：492.525g/mol
Molecular Formula：C₂₄H₃₂N₂O₉
Compound Is Canonicalized：True
XLogP3-AA：492.21078060
Monoisotopic Mass：492.21078060
Complexity：638
Rotatable Bond Count：12
Hydrogen Bond Donor Count：4
Hydrogen Bond Acceptor Count：10
Topological Polar Surface Area：171
Heavy Atom Count：：35
Defined Atom Stereocenter Count：3
Undefined Atom Stereocenter Count：0
Defined Bond Stereocenter Count：1
Undefined Bond Stereocenter Count：0
Isotope Atom Count：0
Covalently-Bonded Unit Count：2
CACTVS Substructure Key Fingerprint：AAADcfB7PAAAAAAAAAAAAAAAAAAAAWAAAAAwAAAAAAAAAAABAAAAHgAQCAAADCjhmAYyCIPABgCIAiHSGAACAAAgAAAIiIGIAMgKZDKAkTCXcAAklgCYmYeY2bKOAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==

9.Other Information

Usage: Enalapril maleate salt is used as a long-acting ACE inhibitor and antihypertensive, used to study diabetic angiopathy in diabetic rats and inhibition of ACE in hog plasma (I50=1.2nM). ACE inhibitors disturb the enin-angiotensin- aldosterone system. Additional ACE inhibitors include: Enalapril, Enalaprilat dihydrate, Enalaprilat, and Enalapril-d5 Maleate Salt, among others.

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Merck: 14,3567

Target: Value

Description: Enalapril maleate is the second angiotensin converting enzyme inhibitor to reach the marketplace. Like captopril, the first entry in this area, enalapril is useful in the treatment of hypertension and congestive heart failure. It has a longer effective half-life than captopril, allowing once or twice-daily dosing, and appears to have a somewhat lower incidence of side effects.

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Chemical Properties: White to Off-White Crystalline Powder

Originator: Merck (USA)

Uses: sunscreen

Uses: An antihypertensive. An angiotensin-converting enzyme (ACE) inhibitor.

Definition: ChEBI: The maleic acid salt of enalapril. It contains one molecule of maleic acid for each molecule of enalapril. Following oral administration, the ethyl ester group of enalapril is hydrolysed to afford the corresponding carboxylic acid, enalaprilat, an angioten in-converting enzyme (ACE) inhibitor. Enalapril is thus a prodrug for enalaprilat (which, unlike enalapril, is not absorbed by mouth), and its maleate is used in the treatment of hypertension and heart failure, for reduction of proteinuria and renal diseas in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients.

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Manufacturing Process: N-[1(S)-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline maleic acid salt
A mixture of 3 g of L-alanyl-L-proline, 5 g of ethyl 2-oxo-4-phenyl-butanoate, 13 g of 3A molecular sieves, and 3.6 g of Raney nickel in 85 ml of ethanol is hydrogenated at 25°C and at 40 psig of hydrogen until uptake of hydrogen ceases. The solids are filtered, washed with 80 ml of ethanol and the filtrates are combined. Assay by high pressure liquid chromatography shows an 87:13 ratio of diastereoisomers in favor of the desired product. Ethanol is removed under vacuum to afford an oil which is dissolved in 60 ml of water and 20 ml of ethyl acetate. The pH of the stirred two-phase mixture is adjusted to 8.6 with 50% NaOH. The layers are separated and the water phase is extracted with 2x20 ml of ethyl acetate. The water phase is adjusted to pH 4.25 with hydrochloric acid, 12 g of NaCl is dissolved in the water, and product is extracted with 5x12 ml of ethyl acetate. The extracts are combined and dried with Na2SO4. The desired product, N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]- L-alanyl-L-proline, is crystallized as its maleate salt by addition of 1.86 g of maleic acid. After stirring for 4 hours, the salt is filtered, washed with ethyl acetate and dried to afford 5.2 g of pure product, melting point 150°-151°C.

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Brand name: RENITEN

Therapeutic Function: Antihypertensive

General Description: Enalapril maleate, 1-[N[(S)-1-carboxy-3-phenylpropyl]-L-alanyl]-L-proline 1 -ethyl estermaleate (Vasotec), is a long-acting ACE inhibitor. It requiresactivation by hydrolysis of its ethyl ester to form thediacid enalaprilat. Enalapril is devoid of the side effects ofrash and loss of taste seen with captopril. These side effectsare similar to those of the mercapto-containing drugpenicillamine. The absence of the thiol group in enalaprilmaleate may free it from these side effects. The half-life is11 hours.

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Biochem/physiol Actions: A long-acting angiotensin-converting enzyme inhibitor.

Veterinary Drugs and Treatments: The principle use of enalapril/enalaprilat in veterinary medicine at present is as a vasodilator in the treatment of heart failure. Recent studies have demonstrated that enalapril, particularly when used in conjunction with furosemide, does improve the quality of life in dogs with heart failure. It is not clear, however, whether it has any significant effect on survival times. It may also be of benefit in treating the effects associated with valvular heart disease (mitral regurgitation) and left to right shunts. It is being explored as adjunctive treatment in chronic renal failure and protein losing nephropathies.
While ACE inhibitors are a mainstay for treating hypertension in humans, they have not been particularly useful in treating hypertension in dogs or cats.

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10. Toltal 354 Suppliers View more

USP standard Enalapril maleate CAS 76095-16-4 supplied by manufacturer

Wuhan Fortuna Chemical Co., Ltd.

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Tel: Update Time:2024/08/08

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Baoji Guokang Healthchem co.,ltd

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Amitychem Corporation

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Wuhan Circle Star Chem-medical Technology Co.,Ltd

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Dayang Chem (Hangzhou) Co., Ltd.

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11. Related Questions

: What is Enalapril maleate and how does it work?Enalapril maleate, chemically known as N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-prolyl-L-alanine 1-butanediamine salt, is a novel antihypertensive drug developed by Merck in the United States in 19..; What are the uses, dosage, side effects, and pharmacokinetics of Enalapril maleate?Enalapril maleate is indicated for the treatment of primary hypertension, renal vascular hypertension, all stages of heart failure, and prevention of symptomatic heart failure. Usage and Dosage Oral a..; How to synthesize and purify Enalapril maleate?Background and overview[1] Enalapril maleate (Enalapril Maleate), also known as Enalapril Maleate, CAS registration number: 76095-16-4, chemical name: N-[(s)-ethoxycarbonyl-3-phenylpropyl]-L-propyl Am..; What are the medicinal values of Enalapril maleate? High blood pressure is a relatively common condition, and it is important to regularly measure it and take appropriate antihypertensive medications. It is also crucial to manage emotions and avoid fl..

12. Realated Product Infomation