Menozzi Giulia, Merello Luisa, Fossa Paola, Mosti Luisa, Piana Antonietta, Mattioli Francesca
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy.
Farmaco. 2003 Sep;58(9):795-808. doi: 10.1016/S0014-827X(03)00136-8.
A number of 5-aryl-1-[4-(methylsulfonyl)-phenyl]-1H-pyrazoles and 4-(5-aryl-1H-pyrazol-1-yl)benzenesulfonamides 3, 4, 5, 6, analogues of the COX-2 selective inhibitor celecoxib (celebrex), were synthesized. In order to verify the effects on the biological properties of certain substituents put on position 4 of the pyrazole nucleus, some of these compounds were screened in vivo for their anti-inflammatory and analgesic activities. Moreover, sodium salts of carboxylic acids 4 were tested in vitro for their platelet anti-aggregating properties. The results of these preliminary biological assays showed that new derivatives are not endowed with improved anti-inflammatory and analgesic properties, in comparison with celecoxib. In addition, docking studies were carried out on the most significative compounds to evaluate their interaction mode at the active site of both COX-1 and COX-2. Some remarks about the SAR of this class of COX-inhibitors are drown out.
合成了多种5-芳基-1-[4-(甲基磺酰基)-苯基]-1H-吡唑以及4-(5-芳基-1H-吡唑-1-基)苯磺酰胺3、4、5、6，它们是COX-2选择性抑制剂塞来昔布（西乐葆）的类似物。为了验证吡唑核4位上某些取代基对生物学性质的影响，对其中一些化合物进行了体内抗炎和镇痛活性筛选。此外，还对羧酸4的钠盐进行了体外血小板抗聚集性能测试。这些初步生物学试验的结果表明，与塞来昔布相比，新衍生物没有更好的抗炎和镇痛性能。此外，对最有意义的化合物进行了对接研究，以评估它们在COX-1和COX-2活性位点的相互作用模式。得出了关于这类COX抑制剂构效关系的一些结论。
