LAUSR

Graphical abstract Figure. No Caption available. HighlightsFirst reported 17&bgr;‐amide derivatives of 2‐methoxyestradiol.The single crystal X‐ray diffraction confirmed the configuration of 17&bgr;‐butyrylamino of 6c.Three derivatives had similar or even better effects than 2‐ME in antiproliferative assay.Pharmacokinetic tests showed that the half‐life of 6c was ten times that of 2ME. Abstract A series of 17&bgr;‐amide‐2‐methoxyestradiol compounds were synthesized with an aim to enhance the antiproliferative effect of 2‐methoxyestradiol. The antiproliferative activity of 2‐methoxyestradiol analogs against human cancer cells was investigated. 2‐methoxy‐3‐benzyloxy‐17&bgr;‐chloroacetamide‐1,3,5(10)‐triene (5e) and 2‐methoxy‐3‐hydroxy‐17&bgr;‐butyramide‐1,3,5(10)‐triene (6c) had comparable or better antitumor activity than 2‐methoxyestradiol. The elimination half‐life of 6c (t1/2&bgr; = 240.93 min) is ten times longer than 2‐ME and the area under the curve was seven times (AUC0‐tmin = 2068.20 ± 315.74 &mgr;g mL−1 min) higher than 2‐ME, respectively. Whereas 5e had similar pharmacokinetic behavior with 2‐ME (t1/2&bgr; = 22.28 min) with a t1/2&bgr; of 29.5 min. 6c had higher blood concentration, longer actuation duration and better suppression rate against S180 mouse ascites tumor than 2‐methoxyestradiol.