Clidanac

Originator

Indanal,Takeda,Japan,1981

Uses

Clidanac can be used as a replacement for retinol for skin treatment, to treat anal fissures, and as a preparation of ester prodrugs of NSAIDs.

Definition

ChEBI: Clidanac is an organic molecular entity.

Manufacturing Process

N-chlorosuccinimide (8.2 g.0.0614 mol) was added to a stirred, cooled (icewater) solution of (±)-5-cyclohexyl-1-indancarboxylic acid (10.0 g, 0.0409 mol) in dimethylformamide (82 ml). The solution was stirred for fifteen minutes at 0°C. thirty minutes at 25°C. nine hours at 50°C, followed by eight hours at 25°C. The solution was diluted with cold water (400 ml) and stirred until the precipitated product turned granular (fifteen minutes). The crude product was collected, washed with cold water, and dried. Crystallization from Skellysolve B with charcoal treatment gave colorless crystals (6.65 g, 58%), MP 149°C to 150°C. The product was recrystallized twice from Skellysolve B to give (±)-6-chloro-5-cyclohexyl-1-indancarboxylic acid as colorless crystals, MP 150.5°C to 152.5°C.

Therapeutic Function

Antiinflammatory, Antipyretic

Synthesis Reference(s)

Journal of Medicinal Chemistry, 15, p. 1297, 1972 DOI: 10.1021/jm00282a024

Trade name

Britai (Bristol Banyu, Japan), Indanal (Takeda, Japan).

Clinical Use

Clidenac is used for the relief of pain and in- flammation related to arthrosis deformans, periarthritis humeroscapularis, cervical syndrome, and lumbago.

Synthesis

Synthesis: formylation of cyclohexylbenzene using dichloromethyl methyl ether and titanium tetrachloride gives 4- cyclohexylbenzaldehyde, which is condensed with diethyl malonate to yield diethyl 4- cyclohexylbenzylidenemalonate. Treatment of the latter with potassium cyanide in ethanol at 70 ?C gives ethyl 3-cyano-3-(4- cyclohexylphenyl)propionate, which is converted to 4-cyclohexylphenylsuccinic anhydride following acid hydrolysis and treatment with refluxing acetic anhydride. An intramolecular Friedel – Crafts acylation (aluminum chloride – methylene chloride) affords 5-cyclohexyl-3-oxo-1-indanecarboxylic acid, which is catalytically reduced using 10 % palladium on charcoal in the presence of perchloric acid to give 5-cyclohexyl-1-indanecarboxylic acid. Chlorination using N-chlorosuccinimide in N,N-dimethylformamide (DMF) gives clidenac.

Raw materials

Preparation Products