替莫唑胺1999年1月首在歐洲獲批治療膠質(zhì)母細(xì)胞瘤（腦癌）上市后，迅速得到全世界幾十個國家的批準(zhǔn)，已經(jīng)成為年銷售額超10億美元的重磅炸彈藥物，它與放療結(jié)合是神經(jīng)膠質(zhì)瘤化療的首選通用方案。通過記述參與研究替莫唑胺20年經(jīng)歷，描述了發(fā)現(xiàn)替莫唑胺這個化合物的化學(xué)結(jié)構(gòu)與活性關(guān)系交融發(fā)展的演變過程，又揭示了將替莫唑胺內(nèi)在的活性在臨床上表現(xiàn)出來所經(jīng)受的坎坷，講述了親身開展替莫唑胺類產(chǎn)品深度開發(fā)研究工作的失敗與成功。

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.