Description
Acemetacin is used in the treatment of pain
and restricted mobility resulting from chronic
articular rheumatism, degenerative articular disease, gout, and inflammation of muscle, joints,
and tendons. Acemetacin causes less gastrointestinal blood loss than indomethacin. Its anti-inflammatory activity results from liberation of
the parent compound, indomethacin.
Chemical Properties
Light Yellow Solid
Originator
Rantudil ,Bayer ,W. Germany ,1980
Uses
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
Definition
ChEBI: A carboxylic ester that is the carboxymethyl ester of indometacin. A non-steroidal anti-inflammatory drug, it is used in the treatment of rheumatoid arthritis, osteoarthritis, and low back pain, as well as for postoperative pain and inflammation. Its activ
ty is due to both acemetacin and its major metabolite, indometacin.
Manufacturing Process
25.4 g (0.050 mol) of [1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-
indoleacetoxy]-benzyl acetate were dissolved in 400 ml of glacial acetic acid
and hydrogenated on 2.0 g of palladium carbon at room temperature. After
the absorption of hydrogen had finished (1 hour), the catalyst was filtered off,
the filtrate was concentrated by evaporation under vacuum and the compound
was caused to crystallize by adding petroleum ether. The compound melted at
149.5-150.5°C (determined on the micro-Kofler bench); the yield was 19.4 g
which corresponds to 93% of the theoretical yield.
The starting material for the above step may be prepared as follows: 5 g
(0.016 mol) of N1-(p-methoxyphenyl)-p-chlorobenzhydrazide hydrochloride
and 4.75 g (0.018 mol) of benzyl levulinoyloxyacetate were heated in 25 ml of
glacial acetic acid for 3 hours at 80°C. The solvent was then evaporated off
under vacuum. The residue was taken up in chloroform and the solution was
washed neutral by shaking with sodium bicarbonate solution and thereafter
with water. After drying the chloroform solution, this was subjected to
chromatography on aluminium oxide, the eluate was concentrated by
evaporation and the viscous oil remaining as residue was crystallized by
adding ether. The compound melted at 94-95°C. The yield was 4.1 g which
corresponds to 50.7% of the theoretical yield.
Therapeutic Function
Antiinflammatory
Trade name
Acemetacin (Heumann, Stada,
Germany), Acemix (Bioprogress, Italy), Altren (Rh?one-Poulenc Rorer, Belgium), Emflex
(Merck, UK), Rantudil (Bayer Pharma Deutschland, Germany)
Clinical Use
Acemetacin is a nonsteroidal
anti-inflammatory drug acting directly
and via its major metabolite indomethacin.
Acemetacin is used in chronic joint pain as well
as in postoperative pain.
Safety Profile
Poison by ingestion, subcutaneous,intraperitoneal, intravenous, and intramuscular routes. Anexperimental teratogen. Other experimental reproductiveeffects. When heated to decomposition it emits toxic fumesof Cl?? and NOx. An anti-inflammatory agent.
Synthesis
alkylation of indomethacin with
benzyl bromoacetate in K2CO3/N,N-dimethylformamide gives the corresponding benzyl glycolate ester, which is hydrogenated over
10 % palladium on charcoal in acetic acid to
yield acemetacin.
References
[1] Patent: CN108440374, 2018, A. Location in patent: Paragraph 0023-0028; 0030-0035; 0037-0042; 0044-0049; 0051-0
[2] Journal of Medicinal Chemistry, 2009, vol. 52, # 10, p. 3348 - 3353
[3] Arzneimittel-Forschung/Drug Research, 1980, vol. 30, # 8 A, p. 1314 - 1325
