Benazepril hydrochloride (Ref: CGS 14824A)

Benazepril hydrochloride (Ref: CGS 14824A)	Last updated: 12/09/2025
(Also known as: benazepril HCl )

GENERAL INFORMATION

Description

A phenylpropylamine medicinal prodrug which is a second generation ACE inhibitor

Examples of veterinary uses

Used to treat congestive heart failure, high blood pressure and chronic renal failure

Examples of species treated

Dogs; Cats

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

Benazepril hydrochloride exhibits optical isomerism due to the presence of two stereogenic centres in its molecular structure. This gives rise to four possible stereoisomers: two pairs of enantiomers: (S,S) and (R,R), and two diastereomers: (S,R) and (R,S). The clinically used form is the (S,S)-enantiomer, which has been shown to possess the desired pharmacological activity as an ACE inhibitor for treating hypertension. The other isomers, particularly the (R,R) enantiomer and the diastereomeric forms, are considered impurities and are typically removed during synthesis and purification to ensure optical purity. Studies have shown that under stress conditions, the (S,S) form remains stereochemically stable and does not convert into other isomers, although degradation may occur.

Chemical formula

C₂₄H₂₉N₂O₅Cl

Canonical SMILES

CCOC(=O)C(CCC1=CC=CC=C1)NC2CCC3=CC=CC=C3N(C2=O)CC(=O)O.Cl

Isomeric SMILES

CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]2CCC3=CC=CC=C3N(C2=O)CC(=O)O.Cl

International Chemical Identifier key (InChIKey)

VPSRQEHTHIMDQM-FKLPMGAJSA-N

International Chemical Identifier (InChI)

InChI=1S/C24H28N2O5.ClH/c1-2-31-24(30)20(14-12-17-8-4-3-5-9-17)25-19-15-13-18-10-6-7-11-21(18)26(23(19)29)16-22(27)28;/h3-11,19-20,25H,2,12-16H2,1H3,(H,27,28);1H/t19-,20-;/m0./s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Medicinal drug, Hypertensive agent, Prodrug

Substance groups

Phenylpropylamine

Minimum active substance purity

>99%

Known relevant impurities

Substance origin

Synthetic

Mode of action

A second generation ACE (angiotensin-converting enzyme) inhibitor which prevents the catalytic conversion of angiotensin I to angiotensin II and in turn causes vasodilation and an increase in capillary blood volume

Molecular targets

[Angiotensin-converting enzyme, Antagonist]

CAS RN

86541-74-4

EC number

CIPAC number

US EPA chemical code

PubChem CID

5362123

Therapeutic Class

Alimentary tract & metabolism: Agents acting on the renin-angiotensin system; ACE inhibitor

ATCvet Code

QC09AA07

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

460.96

PIN (Preferred Identification Name)

IUPAC name

2-[(3S)-3-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid;hydrochloride

CAS name

S-(R*,R*))-1H-1-benzazepine-1-acetic acid,3-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-2,3,4,5-tetrahydro-2-oxo-monohydrochloride

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Off-white crystalline solid

Related substances & organisms

benazepril

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1981, patented; 1990, first medical use

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

Ecuphar NV
Elanco Europe Ltd
Industrial Veterinaria S.A.

Example products using this active

Benazecare Flavour Tablets
Fortekor Tablets
Arixil Vet Tablets

Formulation and application details

Usually supplied in tablet form for oral administration

Commercial production

Benazepril hydrochloride is synthesised through a multi-step chemical process involving key intermediates and stereoselective reactions. The production begins with the reaction of 3-bromo-2,3,4,5-tetrahydro-1H-benzazepine-2-ketone-1-tert-butyl acetate with (S)-homophenylalanine, forming a benazepril intermediate via dynamic kinetic resolution, which ensures high stereochemical purity. This intermediate then undergoes esterification, followed by the introduction of hydrogen chloride gas to convert it into the hydrochloride salt.

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)

34000

High

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

Melting point (°C)

189

Boiling point (°C)

691

Degradation point (°C)

Flashpoint (°C)

372

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

6.76 X 10^-01

Calculated

Log P

-0.17

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

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

benazeprilat
Note: Pharmacologically active

Human (Liver)

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 5000

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)

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

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

> 100

Danio rerio

Low

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

> 1000

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)

> 5000

Rat

Low

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

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

Metabolised in the liver to the active substance Benazeprilat. Equally excreted by both liver and kidney. Also excreted in breast milk and unmetabolized in faeces.

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

No data found

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 diarrhoea, hypotension; disturbances in heart rhythm

Handling issues

Property

Value and interpretation

General

Incompatible with oxidising agents
Emits toxic fumes in a fire

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

benazepril hydrochloride

French

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Italian

Spanish

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Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	12/09/2025
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