Nawrocka W, Sztuba B, Opolski A, Wietrzyk J, Kowalska M W, Głowiak T
Department of Technology of Drugs, Wroclaw University of Medicine, Nankier Sq. 1, 50-140 Wroclaw, Poland.
Arch Pharm (Weinheim). 2001 Jan;334(1):3-10. doi: 10.1002/1521-4184(200101)334:1<3::aid-ardp3>3.0.co;2-2.
The reaction of 2,2,4-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-tetrahydro-1,5-benzodiazepine (3) and 1-cinnamoyl-2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepine (4), were synthesized by the reduction of 1 and 2 using NaBH4 in i-PrOH and two other derivatives 5 and 6 were obtained by reaction of 4 with equimolar and dimolar quantity of cinnamoyl chloride, respectively. The structures of 1-6 were confirmed by analytical and spectral data (IR, 1H NMR, and MS). 7-Carboxy-2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (7) was synthesized and its crystals were subjected to X-ray analysis. Benzodiazepines 1-6 were evaluated for antiproliferative activity in vitro. 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).
描述了2,2,4-三甲基-1H-2,3-二氢-1,5-苯并二氮杂䓬（1）与肉桂酰氯反应生成1-肉桂酰衍生物2的过程。通过在异丙醇中用硼氢化钠还原1和2合成了两种新型苯并二氮杂䓬，即2,2,4-三甲基-1H-2,3,4,5-四氢-1,5-苯并二氮杂䓬（3）和1-肉桂酰-2,2,4-三甲基-1H-2,3,4,5-四氢-1,5-苯并二氮杂䓬（4），并且分别通过4与等摩尔和二摩尔量的肉桂酰氯反应得到了另外两种衍生物5和6。通过分析和光谱数据（红外光谱、1H核磁共振谱和质谱）确定了1-6的结构。合成了7-羧基-2,2,4-三甲基-1H-2,3-二氢-1,5-苯并二氮杂䓬（7）并对其晶体进行了X射线分析。对苯并二氮杂䓬1-6进行了体外抗增殖活性评估。在所测试的化合物中，4-6对人癌细胞系，即SW707（结肠癌）、MCF-7（乳腺癌）、A549（肺癌）和HCV29T（膀胱癌）表现出细胞毒性活性。
