沙利度胺的结构修饰与生物活性研究进展

Advances in the study of structural modification of thalidomide and its biological activities

沙利度胺是一种合成类谷氨酸衍生物,在1957年作为镇静和止吐的非巴比妥类药物在德国上市,后因致畸作用而被禁止生产和销售。近年来,大量研究表明沙利度胺具有广泛的药理活性,包括抑制血管生成、抗炎、抗肿瘤、镇痛、抗纤维化等。虽然沙利度胺具有广泛的生物学活性,但因水溶性差、口服生物利用度低、药代动力学性质差等特点限制了其临床应用。为了克服这些缺点,国内外研究人员通过对沙利度胺母体骨架进行化学修饰,设计并开发了大量结构新颖、活性强的沙利度胺衍生物。综述了近20年来沙利度胺的结构修饰与其活性研究进展,为沙利度胺衍生物的进一步开发提供参考。

Thalidomide,a synthetic glutamate derivative,was marketed in Germany in 1957 as a sedative and antiemetic nonbarbiturate and was later banned from production and sale because of its teratogenic effects.In recent years,the pharmacological effects of thalidomide have been extensively studied,and many studies have demonstrated that thalidomide possesses a variety of pharmacological activities,including inhibition of angiogenesis,anti-inflammation,anti-tumor activity,analgesic and anti-fibrotic.Although thalidomide has a wide range of biological activities,its poor aqueous solubility,low oral bioavailability,and poor pharmacokinetic properties limit its use in clinical practice.To overcome these shortcomings,domestic and foreign researchers have designed and developed a large number of structurally novel and active thalidomide derivatives by chemically modifying the thalidomide parent skeleton.The progress of the structural modification of thalidomide and its activity in the past 20 years is summarized to provide a reference for the further development of thalidomide derivatives.