Two new series of pyrazolo[3,4-d]pyrimidine bearing thiazolidinone moiety were designed and synthesized. The newly synthesized compounds were evaluated for their in vitro (COX-1 and COX-2) inhibitory assay. Compounds that showed promising COX-2 selectivity were further subjected to in vivo anti-inflammatory screening applying formalin induced paw edema (acute model) and cotton-pellet induced granuloma (chronic model) assays using celecoxib and diclofenac sodium as reference drugs. The histopathological and ulcerogenic potential were also determined. In vivo anti-inflammatory data showed that compounds 2, 6, 7d displayed anti-inflammatory activity higher than both references in the formalin induced paw edema model. On the other hand, compounds 2, 3d, 3e, 7b and 7d displayed anti-inflammatory activity greater than or nearly equivalent to diclofenac sodium in the cotton pellet-induced granuloma assay. Moreover, most of the tested compounds revealed good gastrointestinal safety profile. Collectively, compounds 2 and 7d were considered as promising candidates in managing both acute and chronic inflammation with safe gastrointestinal margin.

设计并合成了两个带有噻唑烷酮部分的吡唑并[3,4- d ]嘧啶的新系列。评价新合成的化合物的体外（COX-1和COX-2）抑制性测定。使用塞来昔布和双氯芬酸钠作为参比药物，使用福尔马林诱导的爪水肿（急性模型）和棉丸诱导的肉芽肿（慢性模型）测定法进一步对显示出有希望的COX-2选择性的化合物进行体内抗炎筛选。还确定了组织病理学和溃疡致病性。体内抗炎数据表明，化合物2，6，7天在福尔马林诱发的爪水肿模型中显示的抗炎活性高于两个参考文献。在另一方面，化合物2，3D，3E，图7b和图7d显示抗炎活性大于或几乎等同于棉球诱导的肉芽肿测定双氯芬酸钠。此外，大多数测试化合物显示出良好的胃肠道安全性。总体而言，化合物2和7d被认为是在安全的胃肠道边缘处理急性和慢性炎症中很有希望的候选者。