Imrecoxib

Uses

Imrecoxib (BAP-909) is a novel and selective cyclooxygenase 2 (COX-2) inhibitor with an IC50 value of 18 nM, it also inhibits COX1- activity with an IC50 value of 115 nM. Imrecoxib (BAP-909) has anti-inflammatory effect[1].

Clinical Use

Imrecoxib, a new non-steroid anti-inflammtory drug (NSAID), was launched in China with the trade name of Hengyang® for the treatment of osteoarthritis in 2012. It was originally designed and synthesized by Guo and co-workers at the Institute of Materia Medica (IMM) of the Chinese Academy of Medical Sciences in collaboration with Hengrui Pharmaceuticals. Imrecoxib, which is a moderately selective COX-2 inhibitor (with IC50 values against COX-1 and COX-2 being 115 ± 28 nM and 18 4 nM, respectively).

Synthesis

Imrecoxib has had two synthetic routes reported across several publications. The most likely process-scale route to this drug is described in the scheme, which began with 2-bromo-4'-(methylsulfonyl)-acetophenone (84) and p-tolylacetic acid (85) as starting materials. In the presence of base, |á-bromoketone 84 was treated with acid 85 which resulted in lactone 86 in 72% yield across the two-step sequence. Exposure of lactone 86 with propylamine triggered a ring-opening-ring closing reaction, which resulted in imrecoxib (XIII) directly in 85% yield.

in vivo

IC 50

Human COX-1: 115 nM (IC₅₀); Human COX-2: 18 nM (IC₅₀)

References

[1] Chen XH, et al. Imrecoxib: a novel and selective cyclooxygenase 2 inhibitor with anti-inflammatory effect. Acta Pharmacol Sin. 2004 Jul;25(7):927-31. PMID:15210067