Cimicoxib

Cimicoxib

Names
Preferred IUPAC name 4-[4-Chloro-5-(3-fluoro-4-methoxyphenyl)-1H-imidazol-1-yl]benzene-1-sulfonamide
Identifiers
CAS Number	265114-23-6^Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:76127
ChEMBL	ChEMBL435381
ChemSpider	184745
ECHA InfoCard	100.170.774
PubChem CID	213053
UNII	W7FHJ107MC^Y
CompTox Dashboard (EPA)	DTXSID30181093
InChI InChI=1S/C16H13ClFN3O3S/c1-24-14-7-2-10(8-13(14)18)15-16(17)20-9-21(15)11-3-5-12(6-4-11)25(19,22)23/h2-9H,1H3,(H2,19,22,23) Key: KYXDNECMRLFQMZ-UHFFFAOYSA-N InChI=1/C16H13ClFN3O3S/c1-24-14-7-2-10(8-13(14)18)15-16(17)20-9-21(15)11-3-5-12(6-4-11)25(19,22)23/h2-9H,1H3,(H2,19,22,23) Key: KYXDNECMRLFQMZ-UHFFFAOYAQ
SMILES O=S(=O)(c3ccc(n1c(c(Cl)nc1)c2ccc(OC)c(F)c2)cc3)N
Properties
Chemical formula	C16H13ClFN3O3S
Molar mass	381.81 g·mol^−1
Pharmacology
ATCvet code	QM01AH93 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Cimicoxib (UR-8880 trade name Cimalgex) is a nonsteroidal anti-inflammatory drug (NSAID) used in veterinary medicine to treat dogs for pain and inflammation associated with osteoarthritis and for the management of pain and inflammation associated with surgery.^[1] It acts as a COX-2 inhibitor.

Synthesis

The chemical synthesis of Cimicoxib was reported:^[2]

Cimicoxib synthesis

The reaction of N-acetylsulfanilyl chloride [121-60-8] (1) (available from chlorosulfonation of acetanilide) with tert-butylamine, gives N-(4-tert-butylsulfamoyl-phenyl)-acetamide [294885-56-6] (2). The acetyl group on nitrogen is then removed by heating with strong base to give N-tert-butyl 4-aminophenylsulfonamide [209917-48-6] (3). Condensation with 3-fluoro-4-anisaldehyde [351-54-2] (4) gives the anil, i.e. PC11132250 (5), which incorporates the two adjacent aromatic rings characteristic of COX-2 inhibitors. Reaction of the imine with TosMIC [36635-61-7] in the presence of potassium carbonate leads to what may be viewed as 2 + 3 cycloaddition of the nitrogen analogue of a ketene to form the imidazole ring, PC11784436 (6). This ring is then halogenated with N-chlorosuccinimide (NCS) giving PC10274815 (7). Acid hydrolysis of the protecting group gives the free sulfonamide and thus cimicoxib (8).

References

1. "European Public Assessment Report: Cimalgex (cimicoxib)". European Medicines Agency. 17 September 2018. Archived from the original on 15 November 2017. Retrieved 18 April 2012.
2. Almansa, Carmen; Alfón, José; de Arriba, Alberto F.; Cavalcanti, Fernando L.; Escamilla, Ignasi; Gómez, Luis A.; Miralles, Agustí; Soliva, Robert; Bartrolí, Javier; Carceller, Elena; Merlos, Manuel; García-Rafanell, Julián (2003). "Synthesis and Structure−Activity Relationship of a New Series of COX-2 Selective Inhibitors:  1,5-Diarylimidazoles". Journal of Medicinal Chemistry. 46 (16): 3463–3475. doi:10.1021/jm030765s. ISSN 0022-2623. PMID 12877584.