Synthesis and antiproliferative activity in vitro of novel 1,5-benzodiazepines. Part II

The reaction of 2,2,3-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (1) with cinnamoyl chloride leading to the formation of 1-cinnamoyl derivative 2 is described. Two novel benzodiazepines, 2,2,4-trimethyl-1H-2,3,4,5-terrahydro -1,5-benzodiazepine (3) and 1-cinnamoyl-2,2,4-trimethyl- 1H-2,3,4,5-tetrahy dro-1,5-benzodiazepine (4), were synthesized by the reduction of 1 and 2 us ing NaBH4 in i-PrOH and two other derivatives 5 and 6 were obtained by reac tion of 4 with equimolar and dimolar quantity of cinnamoyl chloride, respec tively. The structures of 1-6 were confirmed by analytical and spectral dat a (IR,H-1 NMR, and MS). 7-Carboxy-2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzod iazspine (7) was synthesized and its crystals were subjected to X-ray analy sis. Benzodiazepines 1-6 were evaluated for antiproliferative activity in v itro. Among the compounds tested, 4-6 exhibited cytotoxic activity against human cancer cell lines, namely SW707 (colon cancer), MCF-7 (breast cancer) , A549 (lung cancer), and HCV29T (bladder cancer).