Rao Praveen, Knaus Edward E
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Pharm Pharm Sci. 2008 Sep 20;11(2):81s-110s. doi: 10.18433/j3t886.
NSAIDs constitute an important class of drugs with therapeutic applications that have spanned several centuries. Treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug aspirin to the recent rise and fall of selective COX-2 inhibitors has provided an enthralling evolution. Efforts to discover an ultimate magic bullet to treat inflammation continues to be an important drug design challenge. This review traces the origins of NSAIDs, their mechanism of action at the molecular level such as cyclooxygenase (COX) inhibition, development of selective COX-2 inhibitors, their adverse cardiovascular effects, and some recent developments targeted to the design of effective anti-inflammatory agents with reduced side effects.
Literature data is presented describing important discoveries pertaining to the sequential development of classical NSAIDs and then selective COX-2 inhibitors, their mechanism of action, the structural basis for COX inhibition, and recent discoveries.
A brief history of the development of NSAIDs and the market withdrawal of selective COX-2 inhibitors is explained, followed by the description of prostaglandin biosynthesis, COX isoforms, structure and function. The structural basis for COX-1 and COX-2 inhibition is described along with methods used to evaluate COX-1/COX-2 inhibition. This is followed by a section that encompasses the major chemical classes of selective COX-2 inhibitors. The final section describes briefly some of the recent advances toward developing effective anti-inflammatory agents such as nitric oxide donor NO-NSAIDs, dual COX/LOX inhibitors and anti-TNF therapy.
A great deal of progress has been made toward developing novel anti-inflammatory agents. In spite of the tremendous advances in the last decade, the design and development of a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge.
非甾体抗炎药（NSAIDs）是一类重要的药物，其治疗应用已跨越了几个世纪。从经典药物阿司匹林到选择性COX-2抑制剂的兴起与衰落，类风湿关节炎（RA）和骨关节炎（OA）等炎症性疾病的治疗呈现出引人入胜的演变过程。寻找治疗炎症的终极神奇药物的努力仍然是药物设计的一项重要挑战。本综述追溯了NSAIDs的起源、它们在分子水平上的作用机制（如环氧合酶（COX）抑制）、选择性COX-2抑制剂的开发、它们的不良心血管效应，以及一些针对设计副作用减少的有效抗炎药物的最新进展。
呈现文献数据，描述与经典NSAIDs及随后的选择性COX-2抑制剂的相继开发、它们的作用机制、COX抑制的结构基础以及最新发现相关的重要研究成果。
解释了NSAIDs的简要发展历程以及选择性COX-2抑制剂退出市场的情况，随后描述了前列腺素生物合成、COX同工型、结构与功能。阐述了COX-1和COX-2抑制的结构基础以及用于评估COX-1/COX-2抑制的方法。接着是涵盖选择性COX-2抑制剂主要化学类别的部分。最后一部分简要描述了开发有效抗炎药物（如一氧化氮供体型NO-NSAIDs、COX/LOX双重抑制剂和抗TNF治疗）的一些最新进展。
在开发新型抗炎药物方面已经取得了很大进展。尽管在过去十年中取得了巨大进步，但设计和开发一种安全、有效且经济的炎症性疾病治疗方法仍然是一项重大挑战。
