Department of Pharmaceutical Chemistry, Sree Vidyanikethan College of Pharmacy, Tirupati, India.
Centre for Research Studies, Krishna University, Machillipatnam, India.
Arch Pharm (Weinheim). 2018 Feb;351(2). doi: 10.1002/ardp.201700256. Epub 2017 Dec 28.
Oxaprozin is a popular non-steroidal anti-inflammatory drug (NSAID) and its chronic oral use is clinically restricted due to its gastrointestinal (GI) complications. In order to circumvent the GI complications, oxaprozin was amended as a prodrug in a one-pot reaction using N,N-carbonyldiimidazole as an activating agent. Dextran of average molecular weight (60,000-90,000 Da) was exploited as a carrier in the process of oxaprozin prodrug production by esterification. The structural profiles of the synthesized oxaprozin prodrug were characterized by FT-IR and NMR spectroscopy. The oxaprozin prodrug possessed optimal molecular weight, lipophilicity, partition coefficient, protein binding, and degree of substitution of 52.4%. The release of oxaprozin upon hydrolysis of the prodrug in both simulated gastric fluid and simulated intestinal fluid followed first-order kinetics with 55.2 min of half-life. Varied ADME properties of the prodrug resulted upon Schrodinger's QikProp tool application. Oxaprozin prodrug displayed significant analgesic, antipyretic, and anti-inflammatory activities, with a remarkable decrease in the ulcer index and being devoid of antigenicity in experimental animals. Thus, it is evident that oxaprozin prodrug is a safer oral NSAID without causing any ulcerations.
奥沙普秦是一种常用的非甾体抗炎药（NSAID），由于其胃肠道（GI）并发症，其长期口服在临床上受到限制。为了避免 GI 并发症，奥沙普秦在一锅反应中被修改为前药，使用 N,N-碳二亚胺作为激活剂。在奥沙普秦前药生产过程中，平均分子量（60,000-90,000 Da）的葡聚糖被用作载体进行酯化。合成的奥沙普秦前药的结构特征通过傅里叶变换红外光谱（FT-IR）和核磁共振（NMR）光谱进行了表征。奥沙普秦前药具有最佳的分子量、亲脂性、分配系数、蛋白结合度和取代度为 52.4%。前药在模拟胃液和模拟肠液中的水解释放遵循一级动力学，半衰期为 55.2 分钟。通过使用 Schrodinger 的 QikProp 工具进行应用，前药的 ADME 性质发生了变化。奥沙普秦前药具有显著的镇痛、解热和抗炎活性，在实验动物中溃疡指数显著降低，且无抗原性。因此，奥沙普秦前药是一种更安全的口服 NSAID，不会引起任何溃疡。
