34645-84-6

Usage

Uses

Used in Pharmaceutical Industry:
Fenclofenac is used as an anti-inflammatory agent for the treatment of various conditions characterized by inflammation, pain, and swelling. It is particularly effective for conditions like rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis, where it helps alleviate symptoms and improve the quality of life for patients.
Used in Veterinary Medicine:
Fenclofenac is also utilized in veterinary medicine for managing inflammation and pain in animals. It is commonly prescribed for conditions like soft tissue and orthopedic injuries, as well as for post-operative pain management in pets.
Used as a Protein-Pump Inhibitor:
In addition to its anti-inflammatory effects, fenclofenac functions as a protein-pump inhibitor. This mechanism of action contributes to its ability to reduce inflammation by inhibiting the activity of certain proteins involved in the inflammatory process.
Brand Names:
Fenclofenac is available under various brand names, including Feclan, Gidalon, Monosan, and Rx 67408nac, which are used to distinguish the drug in different markets and for specific formulations.

Originator

Flenac,Reckitt and Colman

Manufacturing Process

1-[2-(2,5-Dichloro-phenoxy)-phenyl]-ethanone was prepared from a mixture of 2,4-dichlorphenol, 2-chloroacetophenone and copper catalyst (prepared according to R.Q. Brewster and T. Groening Organic Syntheses, John Wiley and Sons, Inc., New York, 1943, Coll. Vol.11, p.446). 1 mol of the above phenoxy compound was mixed with 3 mol of sulfur and 3.5 mol of morpholine and heated under gentle reflux for 72 hours. The mixture was evaporated, water was added and extracted with ether. The aueous layer was then acidified with concentrated hydrochloric acid and the product was extracted into ether, the ether extract was dried and evaporated. The solid residue was recrystallized from CCl4 to give [2-(2,4-dichlorophenoxy)-phenyl]acetic acid, Yield 37%; MP: 134°-136°C.

Therapeutic Function

Antiinflammatory

World Health Organization (WHO)

Fenclofenac, a nonsteroidal anti-inflammatory agent, was introduced in 1978 for the treatment of rheumatic disorders. By 1984 its use in the United Kingdom was associated with serious adverse effects, predominantly skin rashes, some of which were fatal. This led to the UK Committee on Safety of Medicine's refusal to renew the product licence and to the subsequent withdrawal of the drug by the manufacturer in all countries in which it was marketed.

Synthesis

Fenclofenac, o-[2,4-dichlorophenoxy)phenyl]acetic acid (3.2.45), is synthesized from 2,4-dichlorophenol and 2-chloroacetophenone, the reaction of which in the presence of sodium hydroxide and powdered copper forms the corresponding 2-acetyl-2′,4′-dichloro-diphenyl ester (3.2.43). The resulting product is reacted with sulfur and morpholine according to Willgerodt method, giving thioamide (3.2.44), which is further hydrolyzed to the desired fenclofenac [109,110].

InChI:InChI=1/C14H10Cl2O3/c15-10-5-6-13(11(16)8-10)19-12-4-2-1-3-9(12)7-14(17)18/h1-6,8H,7H2,(H,17,18)

Upstream product

• 2444-36-2 2'-chloro-benzeneacetic acid 
• 120-83-2 2,4-dichlorophenol 
• 86309-06-0 2-(2,4-dichlorophenoxy)benzaldehyde 
• 3757-76-4 sodium 2,4-dichlorophenolate 
• 70-34-8 2,4-Dinitrofluorobenzene 
• 33838-32-3 potassium 2-formylphenolate 
• 86308-86-3 2-(2,4-dichlorophenoxy)benzoic acid 
• 22446-37-3 methyl (2-hydroxyphenyl)acetate 
• 2142-68-9 1-(2-chlorophenyl)ethanone 
• 86309-00-4 methyl <2-(2,4-diaminophenoxy)phenyl>acetate 
• 86308-85-2 2-[2-(2,4-Dichloro-phenoxy)-phenyl]-acetamide 
• 120-82-1 1,2,4-Trichlorobenzene 
• 118-91-2 ortho-chlorobenzoic acid 
• 6630-33-7 ortho-bromobenzaldehyde 

Downstream Products

• 82298-65-5 2-[2-(2,4-Dichloro-phenoxy)-phenyl]-N-[2-(4-isobutyl-piperidin-1-yl)-propyl]-acetamide 
• 86308-91-0 <2-(2,4-dichlorophenoxy)phenyl>acetohydroxamic acid 
• 86308-89-6 3-<2-(2,4-dichlorophenoxy)phenyl>propionic acid 
• 82298-68-8 C₁₇H₁₄Cl₂O₅ 
• 70458-41-2 <2-(2,4-dichlorophenoxy)phenyl>acetyl chloride 
• 86308-88-5 2-<2-(2,4-dichlorophenoxy)phenyl>ethanol 

Relevant academic research and scientific papers

High molecular weight prodrug derivatives of antiinflammatory drugs

Compounds of the formula 1, PS - O - A - (CH2)n- B - D (1), wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyet-hyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan,A is a carbonyl group or absent,n is zero or a positive integer from 1 to 14,B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and, D is (i) a group of the formula:, R1 - CO - (11), wherein R1-CO- represents the acyl residue of a carboxylic acid drug (R1-COOH) used in the treatment of inflammatory disorders; or (ii) a group of the formula:, R2 - O - (12), wherein R2-O- refers to the C-21 alkoxide residue of a known antiinflammatory steroid (R2-OH) or an alkoxide residue of any other drug or medicament containing a hydroxy functional group used in the treatment of inflammatory disorders; with the proviso that when A is absent, n is 0, and B is absent, then R1-CO- is different from the acyl residue of acetylsalicylic acid;, and non-toxic pharmaceutically acceptable acid addition salts thereof;, and non-toxic pharmaceutically acceptable cation salts thereof. Such compounds are biolabile prodrugs providing controlled release and prolonged duration of action of the parent active antiinflamma-tory agents locally at the administration site after intra-articular, intra-muscular, subcutaneous or extra-dural application while at the same time being highly stable in aqueous solution in the pH range 3--5. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time.

Process for the preparation of 2-(2,4-dichlorophenoxy)-phenylacetic acid

Process for the preparation of 2-(2,4-dichlorophenoxy)phenylacetic acid in which the potassium salts of 2-chlorophenylacetic acid and 2,4-dichlorophenol are reacted in aromatic hydrocarbon solvents at elevated temperatures in the presence of a copper chloride catalyst, followed thereafter by acidification.

Substituted (2-Phenoxyphenyl)acetic Acids with Antiinflammatory Activity. 1

The synthesis and antiinflammatory activity of a series of substituted (2-phenoxyphenyl)acetic acids are described.Initial screening in the adjuvant arthritis test showed that halogen substitution in the phenoxy ring enhanced activity considerably.Ulcerogenic potential, as measured by the minimum ulcerogenic dose (MUD), was low in almost all the acids tested. acetic acid possessed the most favorable combination of potency with low toxicity, including ulcerogenicity, and this compound is now in therapeutic use.

Esters and amides containing the 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetyl moiety

Compounds of the formula STR1 wherein each X, which may be identical or different from the other X, is oxygen or imino; R1 is hydrogen, fluorine, chlorine or bromine; R2 and R3, which may be identical or different from each other, are each hydrogen; unsubstituted or mono-substituted alkyl of 1 to 6 carbon atoms, where the substituent is phenyl or dialkylamino with 1 to 3 carbon atoms in each alkyl moiety; pyridyl; or cycloalkyl of 5 to 7 carbon atoms; R2 and R3, together with each other and the nitrogen atoms to which they are attached, are pyrrolidino, piperidino, hexamethyleneimino, morpholino, N-aryl-piperazino or N-(alkyl of 1 to 3 carbon atoms)-piperazino; A is cycloalkylene of 5 to 7 carbon atoms; unsubstituted or substituted alkylene of 2 to 10 carbon atoms, where the substituents are one to two alkyls of 1 to 3 carbon atoms each, one to two carbalkoxys of 2 to 4 carbon atoms each, one to two phenyls, one to four hydroxyls, one halomethyl, one hydroxymethyl, one alkanoyloxy of 1 to 18 carbon atoms, one alkanoyloxymethyl of 1 to 18 carbon atoms in the alkanoyl moiety or one STR2 where R1, R2 and R3 have the meanings previously defined; or alkylene of 2 to 10 carbon atoms interrupted by oxygen, sulfur, sulfoxide, sulfonyl, phenyl, cyclohexyl, pyridyl, piperazino or unsubstituted or substituted imino, where the substituent on the imino group is alkyl of 1 to 6 carbon atoms, phenyl or phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety; B is the acyl residue of an antiphlogistic carboxylic acid; and their non-toxic, pharmacologically acceptable acid addition salts. The compounds as well as their salts are useful as anti-inflammatories.