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.
