1-(2,6-Dichlorophenyl)-2-indolinone CAS 15307-86-5

Introduction：Basic information about 1-(2,6-Dichlorophenyl)-2-indolinone CAS 15307-86-5, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

1-(2,6-Dichlorophenyl)-2-indolinone Basic information

• Product Name: 1-(2,6-Dichlorophenyl)-2-indolinone
• Synonyms: Diciofenac;1-(2,6-DICHLOROPHENYL)-1,3-DIHYDRO-INDOLE-2-ONE;(N-1-(2,6-DICHLOROPHENYL) -2-INDOLIN-2-ONE;2-[[2,6-Dichlorophenyl] amino] benzeneacetic acid;1-(2,6-DICHLOROPHENYL)-2-INDOLINONE /MEQUITAZINE;1-(2,6-DICHLOROPHENYL)-2-INDOLINONE/INDOLINONE;DICLOFENAC ACID/[2-(2,6-DICHLORO-PHENYLAMINO)-PHENY]-ACETIC ACID;(o-(2,6-dichloroanilino)phenyl)-acetic acid
• CAS: 15307-86-5
• MF: C14H11Cl2NO2
• MW: 296.15
• EINECS: 239-348-5
• Product Categories: Indoles and derivatives;pharmacetical;15307-86-5
• Mol File: 15307-86-5.mol

1-(2,6-Dichlorophenyl)-2-indolinone Chemical Properties

• Melting point: 156-158°
• Boiling point: 412.0±45.0 °C(Predicted)
• density: 1.431±0.06 g/cm3(Predicted)
• storage temp.: Sealed in dry,Room Temperature
• solubility: soluble in Methanol
• pka: pKa 4 (Uncertain)
• form: powder to crystal
• color: White to Almost white
• Water Solubility: 1.278mg/L(30 ºC)
• Merck: 14,3081
• InChI: InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)
• InChIKey: DCOPUUMXTXDBNB-UHFFFAOYSA-N
• SMILES: C1(CC(O)=O)=CC=CC=C1NC1=C(Cl)C=CC=C1Cl
• CAS DataBase Reference: 15307-86-5(CAS DataBase Reference)
• NIST Chemistry Reference: Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-(15307-86-5)
• EPA Substance Registry System: Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]- (15307-86-5)

Safety Information

• RIDADR: 3249
• WGK Germany: WGK 3
• RTECS: AG6310000
• HS Code: 2922.49.2600
• HazardClass: 6.1(b)
• PackingGroup: III
• Storage Class: 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects
• Hazard Classifications: Acute Tox. 3 Oral Aquatic Chronic 2 Repr. 2 STOT RE 1 Oral
• Hazardous Substances Data: 15307-86-5(Hazardous Substances Data)

1-(2,6-Dichlorophenyl)-2-indolinone Usage And Synthesis

Application in Particular Diseases

In Osteoarthritis:
Topical diclofenac in a dimethyl sulfoxide carrier (Pennsaid) is a safe and effective treatment for Osteoarthritis pain. It is thought to act primarily by local inhibition of COX-2 enzymes.

Originator

Voltaren,Fujisawa,Japan,1974

Uses

Diclofenac possesses all of the properties unique to the series of propionic acid drugs, yetin terms of anti-inflammatory and analgesic strength it exceeds that of aspirin, analgin, andibuprofen. It is used in acute rheumatism, rheumatoid arthritis, osteoarthritis, ankylosingspondylitis, arthrosis, back pain, neuralgia, and myalgia. It rarely causes side effects. Themost common synonym is voltaren.

Uses

prostaglandin synthetic inhibitor

Indications

Diclofenac (Voltaren, Cataflam) is approved for usein rheumatoid arthritis, osteoarthritis, ankylosingspondylitis, dysmenorrhea, and topically for the treatment treatmentof ocular inflammation and actinic keratosis.Diclofenac exhibits approximately equal selectivity forCOX-1 and COX-2. The most common adverse reactionsare GI disturbances and headache.A reversible elevationof serum transaminases occurs in 15% of patients.

Definition

ChEBI: Diclofenac is a monocarboxylic acid consisting of phenylacetic acid having a (2,6-dichlorophenyl)amino group at the 2-position. It has a role as a non-narcotic analgesic, an antipyretic, an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, a xenobiotic, an environmental contaminant, a drug allergen and a non-steroidal anti-inflammatory drug. It is a secondary amino compound, an amino acid, a dichlorobenzene, an aromatic amine and a monocarboxylic acid. It is functionally related to a phenylacetic acid and a diphenylamine. It is a conjugate acid of a diclofenac(1-).

Manufacturing Process

Four grams of N-chloroacetyl-N-phenyl-2,6-dichloroaniline and 4 grams ofaluminum chloride are well mixed together and heated for 2 hours at 160°C.The melt is cooled and poured onto about 50 grams of ice while it is stillwarm. The oil which separates is dissolved in 50 ml of chloroform, thechloroform solution is washed with 10 ml of water, dried over sodium sulfateand concentrated under 11 torr. The residue is distilled. The 1-(2,6-dichlorophenyl)-2-indolinone melts at 126°-127°C.
A solution of 186 grams of 1-(2,6-dichlorophenyl)-2-indolinone in 660 ml ofethanol and 660 ml of 2 N sodium hydroxide solution is refluxed for 4 hours.The solution is then cooled and left to stand for 4 hours at 0°-5°C. Thecrystals which form are filtered off and recrystallized from water. The sodiumsalt of 2-(2,6-dichloroanilino)-phenylacetic acid melts at 283°-285°C. Theyield is 97% of theoretical, according to US Patent 3,558,690.

Therapeutic Function

Antiinflammatory

Biological Functions

Diclofenac (Voltaren) is a phenylacetic acid derivativethat is a potent inhibitor of COX and that has analgesic,antiinflammatory, and antipyretic effects. Its use is accompaniedby side effects similar to those of otherNSAIDs. Indications for the drug include rheumatoidarthritis, osteoarthritis, and ophthalmic inflammation(use of an ophthalmic preparation).

Biological Activity

Diclofenac is an orally available, potent and selective nonsteroidal anti-inflammatory drug (NSAID). Diclofenac is used to tre at pain and inflammatory diseases. It inhibits both cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2).

Mechanism of action

Diclofenac is unique among the NSAIDs in that it possesses three possible mechanismsof action: 1) inhibition of the arachidonic acid cyclooxygenase system (3 to 1,000 times more potent than otherNSAIDs on a molar basis), resulting in a decreased production of prostaglandins and thromboxanes; 2)inhibition of the lipoxygenase pathway, resulting in decreased production of leukotrienes, particularly thepro-inflammatory LKB4; and 3) inhibition of arachidonic acid release and stimulation of its reuptake, resulting in areduction of arachidonic acid availability.

Pharmacokinetics

Diclofenac is rapidly and completely (～100%) absorbed on oral administration, with peak plasma levels beingreached within 1.5 to 2.5 hours. The free acid (pKa = 4.0) is highly bound to serum proteins (99.5%), primarilyalbumin. Only 50 to 60% of an oral dose is bioavailable because of extensive hepatic metabolism.

Clinical Use

Diclofenac is synthesized from N-phenyl-2,6-dichloroaniline. It is available in 120 different countries and,perhaps, is the most widely used NSAID in the world. It was introduced in the United States in 1989 but was firstmarketed in Japan in 1974. It ranks among the top prescription drugs in the United States. Diclofenac possessesstructural characteristics of both arylalkanoic acid and the anthranilic acid classes of anti-inflammatory drugs, and itdisplays anti-inflammatory, analgetic, and antipyretic properties.

Synthesis

Diclofenac, 2-[(2,6-dichlorophenyl)-amino]-phenylacetic acid (3.2.42), issynthesized from 2-chlorobenzoic acid and 2,6-dichloroaniline. The reaction of these inthe presence of sodium hydroxide and copper gives N-(2,6-dichlorophenyl)anthranylicacid (3.2.38), the carboxylic group of which undergoes reduction by lithium aluminumhydride. The resulting 2-[(2,6-dicholorphenyl)-amino]-benzyl alcohol (3.2.39) undergoesfurther chlorination by thionyl chloride into 2-[(2,6-dichlorophenyl)-amino]-benzylchloride (3.2.40) and further, upon reaction with sodium cyanide converts into 2-[(2,6-dicholorophenyl)-amino]benzyl cyanide (3.2.41). Hydrolysis of the nitrile groupleads to diclofenac (3.2.42) [107,108].

Metabolism

Four majormetabolites resulting from aromatic hydroxylation have been identified. The major metabolite via CYP3A4 is the4′-hydroxy derivative and accounts for 20 to 30% of the dose excreted, whereas the 5-hydroxy, 3′-hydroxy, and4′,5-dihydroxy metabolites via CYP2C9 account for 10 to 20% of the excreted dose. The remaining drug is excretedin the form of sulfate conjugates. Although the major metabolite is much less active than the parent compound, it mayexhibit significant biological activity, because it accounts for 30 to 40% of all of the metabolic products.

1-(2,6-Dichlorophenyl)-2-indolinone Preparation Products And Raw materials

• Raw materials: Sodium hydroxide-->2,6-Dichloroaniline-->Aluminum chloride
• Preparation Products: DICLOFENAC METHYL ESTER