Amlodipine 2-phthalimide

Amlodipine 2-phthalimide	Last updated: 14/09/2025
(Not known by any other names)

GENERAL INFORMATION

Description

A veterinary and human drug used to slow the heart beat and relax blood vessel walls

Examples of veterinary uses

Typically used to treat secondary hypertension caused by hyperthyroidism, diabetes, kidney disease or cardiomyopathy.

Examples of species treated

Cats; Dogs

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Not approved

Chemical structure

Isomerism

Amlodipine 2-phthalimide is a synthetic derivative of amlodipine, modified by attaching a phthalimide group to the amlodipine scaffold, typically at the 2-position of the dihydropyridine ring. This compound retains the chiral centre found in amlodipine, meaning it exhibits enantiomeric isomerism: the molecule exists as two forms, (R)- and (S)-amlodipine 2-phthalimide. The (S)-enantiomer is generally more pharmacologically active. The addition of the phthalimide group may also introduce conformational isomerism, as the bulky aromatic ring can influence the spatial orientation of the molecule, potentially affecting its binding affinity and metabolic stability.

Chemical formula

C₂₉H₂₉ClN₂O₇

Canonical SMILES

CCOC(=O)C1=C(NC(=C(C1C2=CC=CC=C2Cl)C(=O)OCC)COCCN3C(=O)C4=CC=CC=C4C3=O)C

Isomeric SMILES

International Chemical Identifier key (InChIKey)

NTVITRUDLZBADK-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C29H29ClN2O7/c1-4-38-28(35)23-17(3)31-22(25(29(36)39-5-2)24(23)20-12-8-9-13-21(20)30)16-37-15-14-32-26(33)18-10-6-7-11-19(18)27(32)34/h6-13,24,31H,4-5,14-16H2,1-3H3

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Medicinal drug: Vasodilator agent

Substance groups

Dihydropyridine

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Amlodipine slows the rate at which calcium moves into the heart and blood vessel walls. Calcium channel blocker.

Molecular targets

[Voltage-dependent L-type calcium channel subunit alpha-1C, Inhibitor], [Voltage-dependent calcium channel subunit alpha-2/delta-1, Inhibitor], [Voltage-dependent L-type calcium channel subunit beta-2 , Inhibitor], [Voltage-dependent L-type calcium channel subunit alpha-1D, Inhibitor]

CAS RN

140171-49-9

EC number

CIPAC number

US EPA chemical code

PubChem CID

11157139

Therapeutic Class

Lipid modifying agent: HMG CoA reductase inhibitors, other combinations

ATCvet Code

QC10BX11

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

553.0

PIN (Preferred Identification Name)

IUPAC name

diethyl 4-(2-chlorophenyl)-2-[2-(1,3-dioxoisoindol-2-yl)ethoxymethyl]-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

CAS name

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Related substances & organisms

amlodipine

amlodipine besilate

Commercial

Property

Value

Availability status

Mainly used for research

Introduction & key dates

1986, first approved USA

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

Simson Pharma Limited

Example products using this active

Not available commercially

Formulation and application details

Typically supplied as a crystalline powder for research

Commercial production

Amlodipine 2-phthalimide is synthesised as a protected intermediate in the production of amlodipine. The process begins with the condensation of a substituted benzaldehyde (typically 2-chlorobenzaldehyde), a beta-ketoester, and ethyl 3-amino-4-(2-phthalimidoethoxy)crotonate via a Hantzsch-type reaction to form the 1,4-dihydropyridine ring system. The phthalimide group serves as a protecting moiety for the amino functionality, preventing unwanted side reactions during ring formation. After the reaction is complete, the product is purified, often by crystallization or solvent extraction, to yield amlodipine 2-phthalimide as a stable solid.

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)

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

Melting point (°C)

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

Log P

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 metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

Mouse as besylate variant

High

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 dw soil)

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

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)

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

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)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

Mouse as besylate variant

High

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

Heptic metabolism. Renal excretion accounts for approx. 60% administered. The remainder is eliminated in bile and faeces.

Health issues

Specific human health issues (hazard-based)

Carcinogen

Genotoxic

Endocrine disruptor

No data found

; ; ; ;

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 swelling of ankles or feet
May cause difficult or laboured breathing
Possible liver & heart toxicant

Handling issues

Property

Value and interpretation

General

Will release toxic gases if heated to decomposition
Slightly flammable. May combust at high temperatures

CLP classification 2013

Health: H301, H318, H373
Environment: H400, H410

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

amlodipine 2-phthalimide

French

German

Danish

Italian

Spanish

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	14/09/2025
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