Caturla Francisco, Amat Mercè, Reinoso Raquel F, Córdoba Mónica, Warrellow Graham
Department of Medicinal Chemistry, Almirall Prodesfarma S.A., Research Center, Cardener 68-74, 08024 Barcelona, Spain.
Bioorg Med Chem Lett. 2006 Jun 15;16(12):3209-12. doi: 10.1016/j.bmcl.2006.03.052. Epub 2006 Apr 17.
The preparation of the sulfoxide analogues 2 and 4, and their enantiomeric pure forms is discussed as well as their potential to act as prodrugs to the potent and selective sulfone-containing COX-2 inhibitors rofecoxib and etoricoxib. Sulfoxides 2 and 4 were shown to be effectively transformed in vivo into rofecoxib and etoricoxib, respectively, after oral administration in rats. In the case of sulfoxide 2, both a slightly improved pharmacokinetic profile and a better pharmacological activity in an arthritis model were seen when compared with rofecoxib.
讨论了亚砜类似物2和4及其对映体纯形式的制备，以及它们作为强效和选择性含砜COX-2抑制剂罗非昔布和依托考昔的前药的潜力。在大鼠口服给药后，亚砜2和4分别在体内有效地转化为罗非昔布和依托考昔。就亚砜2而言，与罗非昔布相比，在关节炎模型中观察到其药代动力学特征略有改善，药理活性更佳。
