Enalapril maleate (Ref: MK 421)

Enalapril maleate (Ref: MK 421)	Last updated: 16/09/2025
(Also known as: Renitek)

GENERAL INFORMATION

Description

A veterinary prodrug which is an angiotensin-converting enzyme (ACE) inhibitor

Examples of veterinary uses

Used to treat hypertension, symptomatic heart failure, and asymptomatic left ventricular dysfunction

Examples of species treated

Cats; Dogs

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved - usually available as a prescription only medicine to be authorised by a veterinarian (POM-V)

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Enalapril maleate exhibits stereoisomerism due to the presence of three chiral centres in its molecular structure, which allows for multiple diastereomeric forms such as SSS-, SSR-, and SRS-enalapril isomers. These stereoisomers can arise during synthesis or degradation, and their proportions may shift under stress conditions like heat or pH changes. Additionally, enalapril shows cis-trans isomerism around its amide bond, influenced by solvent polarity and ionisation states.

Chemical formula

C₂₄H₃₂N₂O₉

Canonical SMILES

CCOC(=O)C(CCC1=CC=CC=C1)NC(C)C(=O)N2CCCC2C(=O)O.C(=CC(=O)O)C(=O)O

Isomeric 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

International Chemical Identifier key (InChIKey)

OYFJQPXVCSSHAI-QFPUQLAESA-N

International Chemical Identifier (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

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
enalapril	Parent
enalapril maleate	-

General status

Veterinary substance type

Medicinal drug: hypertension agent

Substance groups

Peptide

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Undergoes biotransformation to the active enalaprilat. An angiotensin-converting-enzyme (ACE) inhibitor; Blocks the angiotensin-converting enzyme.

Molecular targets

[Angiotensin-converting enzyme, Inhibitor]

CAS RN

76095-16-4

Alternative/old CAS RN

75847-73-3

EC number

278-375-7

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Agents acting on the renin-angiotensin system: ACE inhibitors, plain; Antihypertensive drug

ATCvet Code

QC09AA02

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

492.52

PIN (Preferred Identification Name)

(S)-1-(N-(1-(Ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline

IUPAC name

(S)-1-((S)-2-(1-((S)-ethoxycarbonyl)-3-phenyl-propylamino)-propionyl)-pyrrolidine-2-carboxylic acid

CAS name

1-(N-((S)-1-Carboxy-3-phenylpropyl)-L-alanyl)-L-proline 1'-ethyl ester

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

White to off-white crystalline powder

Commercial

Property

Value

Availability status

Current

Introduction & key dates

Early 1980s, developed; 1990s, vet use introduction; 2013, listed UK

Example manufacturers & suppliers of products using this active now or historically

Ceva Animal Health Ltd

Example products using this active

Prilenal Tablets

Formulation and application details

Usually supplied in tablet form for oral administration

Commercial production

Enalapril maleate is synthesised through a multi-step process that begins with the formation of the enalapril base, typically via the condensation of L-alanine derivatives with ethoxycarbonyl compounds, followed by cyclisation to form the proline-containing ester core. This intermediate undergoes further functionalisation to introduce the ethyl ester side chain, which is crucial for oral bioavailability. Once the enalapril base is formed, it is reacted with maleic acid to produce the maleate salt, enhancing stability and solubility.

Impact on climate of production and use

Published GHG data is not available for most pharmaceuticals. However, according to industry, global averages suggest producing 1 kg of a typical active pharmaceutical ingredient can range from 10 to 100 kg CO₂e for small molecule drugs and potentially up to 1000 kg CO₂e for complex biologicals such as vaccines, depending on the drug type, its formulation, complexity of synthesis, solvent recovery, and energy sources used.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

Solubility - In water at 20 °C (mg l⁻¹)

16400

at 25 °C

High

Solubility - In organic solvents at 20 °C (mg l⁻¹)

80.0

Ethanol

200

Methanol

Melting point (°C)

143

Boiling point (°C)

165.3

Degradation point (°C)

Flashpoint (°C)

416.7

Octanol-water partition coefficient at pH 7, 20 °C

1.17 X 10⁰⁰

Calculated

Log P

0.07

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

2.97

pKa(2)=5.35

Vapour pressure at 20 °C (mPa)

Henry's law constant at 25 °C (Pa m³ mol⁻¹)

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

Maximum UV-vis absorption L mol⁻¹ cm⁻¹

Surface tension (mN m⁻¹)

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

DT₅₀ (lab at 20 °C)

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Note

Aqueous hydrolysis DT₅₀ (days) at 20 °C and pH 7

Value

Note

Water-sediment DT₅₀ (days)

Water phase only DT₅₀ (days)

Sediment phase only DT₅₀ (days)

Air degradation

As this parameter is not normally measured directly, a surrogate measure is used: ‘Photochemical oxidative DT₅₀’. Where data is available, this can be found in the Fate Indices section below.

Decay in stored produce DT₅₀

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d (mL g⁻¹)

K_oc (mL g⁻¹)

Notes and range

Freundlich

K_f (mL g⁻¹)

K_foc (mL g⁻¹)

¹/_n

Notes and range

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

Bio-concentration factor

BCF (l kg⁻¹)

CT₅₀ (days)

Known soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

enalapril

Animals inc. humans

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

2973

Rat

Low

Mammals - Short term dietary NOEL

(mg kg⁻¹)

(ppm diet)

Mammals - Chronic 21d NOAEL (mg kg⁻¹ bw d⁻¹)

Birds - Acute LD₅₀ (mg kg⁻¹)

Birds - Short term dietary (LC₅₀/LD₅₀)

Birds - Chronic 21d NOEL (mg kg⁻¹ bw d⁻¹)

Earthworms - Acute 14 day LC₅₀ (mg kg⁻¹)

Earthworms - Chronic NOEC, reproduction (mg kg⁻¹)

Soil micro-organisms

Collembola

Acute LC₅₀ (mg kg⁻¹)

Chronic NOEC (mg kg⁻¹)

Non-target plants

Vegetative vigour ER₅₀ (g ha⁻¹)

Seedling emergence ER₅₀ (g ha⁻¹)

Honeybees (Apis spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Unknown mode acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Chronic

Notes

Bumblebees (Bombus spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Mason bees (Osmia spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Other bee species (1)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Other bee species (2)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Beneficial insects (Ladybirds)

Beneficial insects (Lacewings)

Beneficial insects (Parasitic wasps)

Beneficial insects (Predatory mites)

Beneficial insects (Ground beetles)

Aquatic ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Temperate Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

> 1000

Pimephales promelas

Low

Temperate Freshwater Fish - Chronic 21 day NOEC (mg l⁻¹)

Tropical Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

Temperate Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

354

Daphnia magna

Low

Temperate Freshwater Aquatic invertebrates - Chronic 21 day NOEC (mg l⁻¹)

Tropical Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

Aquatic crustaceans - Acute 96 hour LC₅₀ (mg l⁻¹)

Sediment dwelling organisms - Acute 96 hour LC₅₀ (mg l⁻¹)

Sediment dwelling organisms - Chronic 28 day NOEC, static, water (mg l⁻¹)

Sediment dwelling organisms - Chronic 28 day NOEC, sediment (mg kg⁻¹)

Aquatic Plants (free-floating, fonds growth, fresh) - 7 day (mg l⁻¹)

Aquatic plants (rooted, growth rate, fresh) - 14 day (mg l⁻¹)

Algae - Acute (growth rate, fresh; mg l⁻¹)

Algae - Chronic (growth rate, fresh; mg l⁻¹)

Mesocosm study data

NOEAEC mg l⁻¹

Marine bivalves

HUMAN HEALTH AND PROTECTION

General

Property

Value

Source; quality score; and other information

Interpretation

Threshold of Toxicological Concern (Cramer Class)

High (class III)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

2973

Rat

Low

Mammals - Dermal LD₅₀ (mg kg⁻¹ body weight)

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Subcutaneous LD₅₀ = 1418 mg kg⁻¹

Rat

Intravenous LD₅₀ = 849 mg kg⁻¹

Rat

ADI - Acceptable Daily Intake (mg kg⁻¹ bw day⁻¹)

ARfD - Acute Reference Dose (mg kg⁻¹ bw day⁻¹)

AAOEL - Acute Acceptable Operator Exposure Level (mg kg⁻¹ bw day⁻¹)

AOEL - Acceptable Operator Exposure Level - Systemic (mg kg⁻¹ bw day⁻¹)

Dermal penetration studies (%)

Dangerous Substances Directive 76/464

Exposure Routes

Public

Occupational

Mammalian dose elimination route and rate

Hepatic metabolism, renal excretion. Some evidence of some loss in maternal milk

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

No data found

Respiratory tract irritant

Skin irritant

Skin sensitiser

No data found

Eye irritant

Phototoxicant

No data found

General human health issues

May cause dizziness, low blood pressure, synope and a dry cough
Possible kidney toxicant

Handling issues

Property

Value and interpretation

General

Will produce toxic gases when heated to decomposition
Reactive with oxidising agents

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

enalapril maleate

French

German

Danish

Italian

Spanish

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	16/09/2025
Contact:	aeru@herts.ac.uk
Please cite as:	Lewis, K.A., Tzilivakis, J., Warner, D. and Green, A. (2016) An international database for pesticide risk assessments and management. Human and Ecological Risk Assessment: An International Journal, 22(4), 1050-1064. DOI: 10.1080/10807039.2015.1133242