替莫唑胺1999年1月首在欧洲获批治疗胶质母细胞瘤（脑癌）上市后，迅速得到全世界几十个国家的批准，已经成为年销售额超10亿美元的重磅炸弹药物，它与放疗结合是神经胶质瘤化疗的首选通用方案。通过记述参与研究替莫唑胺20年经历，描述了发现替莫唑胺这个化合物的化学结构与活性关系交融发展的演变过程，又揭示了将替莫唑胺内在的活性在临床上表现出来所经受的坎坷，讲述了亲身开展替莫唑胺类产品深度开发研究工作的失败与成功。

Temozolomide (TMZ) was approved by EMA to market in EU in January 1999 for the treatment of glioblastoma multiforme (brain cancer). After that TMZ was approved by tens of medical regulation authorities worldwide and stepped up into the club of block buster drugs (annual sales exceeding $1 000 000 000). Now TMZ combined with radiation is the standard treatment for brain cancer worldwide. The authors recalled his twenty years experiences of participation in the studies of TMZ and its analogous. First the record entertained us with persistent devoting research work of the structure activity relationship (SAR) of imidazo-1,2,3,5-tetrazin series compounds by Stevens for the thirty years. The luckily ending at TMZ was obtained; and then a hardship to bring TMZ on clinical application to realize TMZ intrinsic activity which could benefit the patients was recalled by a team of chemists and clinicians, finally the success and failure in the depth developments of TMZ and its analogous have been depicted.