89796-99-6

Basic information

• Product Name: Aceclofenac
• Synonyms: ACECLOFENAC;ACECLOFENAC-D2;Airtal;Falcol;Gerbin;Glycolic Acid [o-(2,6-Dichloroanilino)phenyl]acetate Ester;PR-82/3;Preservex
• CAS NO: 89796-99-6
• Molecular Formula: C₁₆H₁₃Cl₂NO₄
• Molecular Weight: 354.18
• EINECS: 205-783-4
• Product Categories: Active Pharmaceutical Ingredients;Intermediates & Fine Chemicals;Pharmaceuticals;Lipid signaling;Aromatics;Free Base API;API;AIRTAL
• Mol File: 89796-99-6.mol
• Article Data: 9

Chemical Properties

• Melting Point: 149-153°C
• Boiling Point: 486 °C at 760 mmHg
• Flash Point: 247.7 °C
• Appearance: off-white to light tan/
• Density: 1.455 g/cm³
• Vapor Pressure: 2.93E-10mmHg at 25°C
• Refractive Index: 1.639
• Storage Temp.: -20°C Freezer
• Solubility: Soluble in DMSO
• PKA: 2.60±0.10(Predicted)
• Water Solubility: 32mg/L(32 oC)
• Merck: 14,22
• CAS DataBase Reference: Aceclofenac(CAS DataBase Reference)
• NIST Chemistry Reference: Aceclofenac(89796-99-6)
• EPA Substance Registry System: Aceclofenac(89796-99-6)

Safety Data

• Hazard Codes: T,N
• Statements: 25-36-50/53
• Safety Statements: 26-45-60-61
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• RTECS: CY1577900
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 89796-99-6(Hazardous Substances Data)

Usage

Description

Aceclofenac is a non-steroidal anti-inflammatory drug (NSAIDs) that is commonly prescribed for people with painful rheumatic conditions such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. The drug should not be given to children, breastfeeding mothers, and people with porphyria. Pregnant women should not also be given aceclofenac as they risk developing patent ductus arteriosus in the neonate.

Mechanism of Action

Aceclofenac acts by inhibiting the effect of natural substances known as cyclooxygenase (COX) enzymes. Notably, these enzymes are responsible for making other chemicals in the body, namely prostaglandins. The prostaglandins are normally produced at sites of damages or injury cause inflammation and pain. By blocking the influence of COX enzymes, production of prostaglandins is minimized, meaning that the swelling and pain is eased.

Precautions

Before taking aceclofenac, it is essential to tell the doctor if one has ever had an allergic reaction to any other NSAID, for instance, diclofenac, aspirin, indomethacin, and naproxen; whether one has allergic disorders such as asthma. It is important to alert the doctor if an individual has a heart condition or problem with circulation or blood vessels. Moreover, inform the physician if one has connective tissue disorder, for instance, lupus erythematosus. One should not take the drug if he/she has high blood pressure or has blood-clotting problems.

Description

Aceclofenac is a nonsteroidal antiinflammatory agent with analgesic and antipyretic properties. It is reported to be useful in the treatment of osteoarthritis, rheumatoid arthritis and pain associated with minor surgical procedures. Compared to ketoprofen in the treatment of rheumatoid arthritis, aceclofenac is substantially faster acting.

Chemical Properties

White Crystalline Solid

Originator

Prodes (Prodesfarma) (Spain)

Uses

Labeled Aceclofenac, intended for use as an internal standard for the quantification of Aceclofenac by GC- or LC-mass spectrometry.

Uses

Aceclofenac is a non-steroidal, anti-inflammatory drug (NSAID) with potent inhibitory activity in several models of inflammation. It is used for the treatment of osteoarthritis and rheumatoid arthritis. It is a Biopharmaceutics classification system class II (BCS class I) drug which has an intermediate half-life of 3-4h and undergoes substantial first pass metabolism. aceclofenac is available either in oral form (tablet) or in topical form (gel).

Definition

ChEBI: Aceclofenac is a monocarboxylic acid that is the carboxymethyl ester of diclofenac. A non-steroidal anti-inflammatory drug related to diclofenac, it is used in the management of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. It has a role as an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, a non-steroidal anti-inflammatory drug and a non-narcotic analgesic. It is a monocarboxylic acid, a carboxylic ester, a secondary amino compound, an amino acid and a dichlorobenzene. It derives from a diclofenac.

Brand name

Airtal; Gerbin

Therapeutic Function

Analgesic, Antiinflammatory

Biochem/physiol Actions

Non-steroidal, anti-inflammatory drug (NSAID), with selectivity for COX-2 over COX-1.

Clinical Use

NSAID and analgesic

Drug interactions

Potentially hazardous interactions with other drugs ACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect; increased risk of nephrotoxicity and hyperkalaemia. Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac (increased risk of side effects and haemorrhage). Antibacterials: possible increased risk of convulsions with quinolones. Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparins, dabigatran and edoxaban - avoid long term use with edoxaban. Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine. Antidiabetic agents: effects of sulphonylureas enhanced. Antiepileptics: possibly increased phenytoin concentration. Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir. Ciclosporin: may potentiate nephrotoxicity Cytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinib. Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect, hyperkalaemia with potassium-sparing diuretics. Lithium: excretion decreased. Pentoxifylline: increased risk of bleeding. Tacrolimus: increased risk of nephrotoxicity.

Metabolism

About two-thirds of a dose is excreted in the urine, mainly as hydroxymetabolites, the principal one being 4-hydroxyaceclofenac. A small amount is converted to diclofenac.

InChI:InChI=1/C16H13Cl2NO4/c17-11-5-3-6-12(18)16(11)19-13-7-2-1-4-10(13)8-15(22)23-9-14(20)21/h1-7,19H,8-9H2,(H,20,21)

Synthetic route

2-((2,6-dichlorophenyl)amino)phenylacetoxyacetic acid tert-butyl ester (139272-68-7) → aceclofenac (89796-99-6)

Conditions	Yield
With hydrogenchloride; acetic anhydride; acetic acid In water at 60℃; for 3h; Temperature;	98.5%
With formic acid In acetone at 65℃; for 0.166667h; Reagent/catalyst; Solvent; Temperature; Microwave irradiation;	96.3%
With aluminum (III) chloride; acetic anhydride; acetic acid at 60 - 65℃; for 2.5h; Reagent/catalyst; Temperature; Large scale;	83%
With trifluoroacetic acid In dichloromethane at 20℃; for 7h;	57%
With formic acid at 40℃;

tert-butyl-[2-(2,6-dichloroanilino) phenyl] acetoxy acetate → aceclofenac (89796-99-6)

Conditions	Yield
With formic acid In toluene at 0 - 35℃; for 2h; Product distribution / selectivity;	95%
With formic acid; trifluoroacetic acid In toluene at 25 - 40℃; for 2.5 - 5.5h; Product distribution / selectivity;
With formic acid In toluene at 0 - 50℃; for 2 - 4.5h; Product distribution / selectivity;

aceclofenac benzyl ester (100499-89-6) → aceclofenac (89796-99-6)

Conditions	Yield
With hydrogen; palladium on activated charcoal

diclofenac sodium (15307-79-6) → aceclofenac (89796-99-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylformamide 2: H2 / Pd/C View Scheme
Multi-step reaction with 2 steps 1: potassium iodide / acetonitrile / 0.25 h / 30 °C / Microwave irradiation 2: formic acid / acetone / 0.17 h / 65 °C / Microwave irradiation View Scheme
Multi-step reaction with 2 steps 1: potassium iodide / ethanol / 3 h / 61 - 65 °C / Large scale 2: acetic acid; acetic anhydride; aluminum (III) chloride / 2.5 h / 60 - 65 °C / Large scale View Scheme

C35H29Cl2NO10 → aceclofenac (89796-99-6)

Conditions	Yield
With simulated intestinalfluid In methanol at 37℃; pH=7.4; Reagent/catalyst; pH-value; Solvent;

1,10-Phenanthroline (66-71-7) + zirconyl nitrate + water (7732-18-5) + aceclofenac (89796-99-6) → C28H22Cl2N3O6Zr(1+)*NO3(1-)*9H2O

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	89.35%

aceclofenac (89796-99-6) → C16H13Cl2NO5 + C14H11Cl2NO3 + 2-[(2,6-dichlorophenyl)amino]phenylacetic acid methyl ester (15307-78-5)

Conditions	Yield
In methanol at 20℃; for 6h; UV-irradiation;	A 7% B 5% C 88%

1,10-Phenanthroline (66-71-7) + copper(II) acetate monohydrate (6046-93-1) + aceclofenac (89796-99-6) → C28H24Cl2CuN3O6(1+)*C2H3O2(1-)*6H2O

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	80.04%

1,10-Phenanthroline (66-71-7) + nickel(II) acetate tetrahydrate (6018-89-9) + aceclofenac (89796-99-6) → C28H24Cl2N3NiO6(1+)*C2H3O2(1-)*3H2O

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	78.08%

1,10-Phenanthroline (66-71-7) + lanthanide(III)chloride heptahydrate + aceclofenac (89796-99-6) → C28H24Cl2LaN3O6(2+)*9H2O*2Cl(1-)

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	76.11%

4-acetaminophenol (103-90-2) + aceclofenac (89796-99-6) → C24H20Cl2N2O5 (1452834-52-4)

Conditions	Yield
With trichlorophosphate In pyridine at 5℃; for 4h;	73%

1,10-Phenanthroline (66-71-7) + zinc(II) acetate dihydrate (5970-45-6) + aceclofenac (89796-99-6) → C28H24Cl2N3O6Zn(1+)*C2H3O2(1-)*3H2O

Conditions	Yield
With potassium hydroxide In acetone for 8h; Reflux;	72.53%

ethanol (64-17-5) + aceclofenac (89796-99-6) → 2-(2-[(2',6'-dichlorophenyl)amino]phenyl)acetoxyacetate

Conditions	Yield
With sulfuric acid for 6h; Reflux;	65%

methanol (67-56-1) + aceclofenac (89796-99-6) → C17H15Cl2NO4 (139272-66-5)

Conditions	Yield
With tert.-butylnitrite at 40℃; for 48h;	63%
With sulfuric acid Reflux;

aceclofenac (89796-99-6) + 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (4064-06-6) → 1,2,3,4-di-O-isopropylidene-D-α-galactopyranose-6-yl 2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)acetic acid

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 4h;	62%

{(1R,2R)-cyclohexane-1,2-diamine}dichloridoplatinum(II) (38780-40-4, 52691-24-4, 61848-70-2, 61848-66-6, 61848-62-2) + aceclofenac (89796-99-6) → C22H26Cl3N3O4Pt

Conditions	Yield
With sodium carbonate; silver nitrate In N,N-dimethyl-formamide at 20℃; for 24h; Darkness;	50%

potassium ethyl methylmalonate (103362-70-5) + aceclofenac (89796-99-6) → ethyl 4-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)-2-methyl-3-oxobutanoate

Conditions	Yield
Stage #1: aceclofenac With 1,1'-carbonyldiimidazole Inert atmosphere; Stage #2: potassium ethyl methylmalonate With magnesium chloride Inert atmosphere;	43%

trans-2-pentenal (1576-87-0) + tert-butylisonitrile (119072-55-8, 7188-38-7) + tert-butyl N-tosyloxycarbamate (105838-14-0) + aceclofenac (89796-99-6) → tert-butyl (2S,3R)-2-{2-(tert-butylamino)-1-[2-(2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetoxy)acetoxy]-2-oxoethyl}-3-ethylaziridine-1-carboxylate

Conditions	Yield
Stage #1: trans-2-pentenal; tert-butyl N-tosyloxycarbamate With (S)-α,α-bis(4-hexylphenylthio)-2-pyrrolidinemethanol trimethylsilylether; sodium carbonate In ethanol; water at 20℃; for 0.666667h; Green chemistry; Stage #2: tert-butylisonitrile; aceclofenac In ethanol; water at 20℃; for 24h; Passerini Condensation; Green chemistry; diastereoselective reaction;	33%

2-nitroxyethylammonium nitrate (4665-58-1) + aceclofenac (89796-99-6) → (N-(2-(nitrooxy)ethyl)carbamoyl)methyl 2-(2-((2,6-dichlorophenyl)-amino)phenyl)acetate (183195-09-7)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride	13%

aceclofenac (89796-99-6) → [2-(2,6-dichloroanilino)phenyl]acetic acid (15307-86-5)

Conditions	Yield
With sodium hydroxide for 3h; Heating;

aceclofenac (89796-99-6) → 4'-hydroxy aceclofenac

Conditions	Yield
With NADPH-generating system In acetonitrile at 37℃; for 3h; pH=7.4; aq. phosphate buffer;

aceclofenac (89796-99-6) + β-cyclodextrine → aceclofenac-β-cyclodextrin (1:1) inclusion complex

Conditions	Yield
In methanol; water for 0.75h;

formaldehyd (50-00-0) + 3,6-dinitro-9H-carbazole (3244-54-0) + aceclofenac (89796-99-6) → C29H20Cl2N4O8 (1246212-64-5)

Conditions	Yield
In methanol Mannich reaction; Cooling with ice; Reflux;

3,6-dinitro-9H-carbazole (3244-54-0) + benzaldehyde (100-52-7) + aceclofenac (89796-99-6) → C35H24Cl2N4O8 (1246212-56-5)

Conditions	Yield
In methanol Mannich reaction; Cooling with ice; Reflux;

3,6-dinitro-9H-carbazole (3244-54-0) + aceclofenac (89796-99-6) + acetaldehyde (75-07-0) → C30H22Cl2N4O8 (1246212-52-1)

Conditions	Yield
In methanol Mannich reaction; Cooling with ice; Reflux;

3,6-dinitro-9H-carbazole (3244-54-0) + aceclofenac (89796-99-6) + 4-dimethylamino-benzaldehyde (100-10-7) → C37H29Cl2N5O8 (1246212-60-1)

Conditions	Yield
In methanol Mannich reaction; Cooling with ice; Reflux;

aceclofenac (89796-99-6) → 2-chloro-2-oxoethyl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate (1227857-41-1)

Conditions	Yield
With thionyl chloride In benzene
With thionyl chloride at 20℃; for 18h; Temperature;
With thionyl chloride In tetrahydrofuran for 1.5h; Microwave irradiation;

aceclofenac (89796-99-6) → 2-[(2,6-dichlorophenyl)amino]-N1-(phenyl)-N4-phenylacetoxyacetamidobenzenesulfonamide (1262333-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / benzene 2: N,N-dimethyl-formamide / 24 h / 10 - 130 °C View Scheme

Upstream product

• 5437-45-6 Benzyl 2-bromoacetate 

Downstream Products

• 89797-00-2 IODIXANOL RELATED COMPOUND D (50 MG) (5-[ACETYL(2-HYDROXY-3-METHYLPROPYL)AMINO]-N,N'-BIS(2,3-DIHYDROXYPROPYL)2,4,6-TRIIODO-1,3-BENZE-NEDICARBOXAMIDE) 
• 89797-01-3 Cuprate(4-), [3-carboxy-1-[4-[[3-[[[(2-carboxy-5-sulfophenyl) azo] phenylmethyl]azo]-2-hydroxy-5-sulfophenyl] amino]-6-[(2-chloro-5-sulfophenyl)amino]-1,3,5-triazin-2-yl]pyridiniumato(7-)]-, trisodium hydrogen 
• 89797-02-4 C.I. Reactive yellow 163 
• 89797-03-5 Pyridinium, 1,1'-[(1-amino-8-hydroxy-3,6-disulfo-2,7-naphthalenediyl)bis[azo(4-sulfo-3,1-phenylene) imino[6-[(4-chloro-3-sulfophenyl)amino]-1,3,5-triazine-4,2-diyl]]]bis[3-carboxy-, dihydroxide, hexasodium salt 
• 89797-56-8 3-imino-5-sulfanylidene-dithiolane-4-carbonitrile 
• 89797-57-9 [1,2,3]thiadiazolo[5,4-d]pyrimidin-5(2H)-one 
• 89797-59-1 tetrazolo[1,5-b]pyridazin-6(5H)-one 
• 89797-62-6 [1,2,5]thiadiazolo[3,4-d]pyrimidine-7(3H)-thione 
• 89797-64-8 1,2,5-Oxadiazole-3-carboxamide,4-cyano-(9CI) 
• 89797-67-1 OXALYL MONOGUANYLHYDRAZIDE 
• 89797-68-2 5-(Ethylthio)-1H-tetrazole 
• 89798-48-1 EINECS 229-788-6 
• 89798-57-2 3-[(dimethylcarbamothioyl)sulfanyl]prop-2-enoic acid 
• 89798-83-4 3-amino-N-(prop-2-en-1-yl)-1H-1,2,4-triazole-1-carbothioamide 

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