Insuasty Braulio, Orozco Fabián, Quiroga Jairo, Abonia Rodrigo, Nogueras Manuel, Cobo Justo
Heterocyclic Compounds Research Group, Department of Chemistry, Calle 13 No. 100-00 Meléndez, Universidad del Valle, A. A. 25360 Cali, Colombia.
Eur J Med Chem. 2008 Sep;43(9):1955-62. doi: 10.1016/j.ejmech.2007.12.005. Epub 2007 Dec 23.
A series of new racemic 4-amino-6-aryl-8-(1,3-benzodioxol-5-yl)-8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 4a-f and 4-amino-8-aryl-6-(1,3-benzodioxol-5-yl)-8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 5a-f were obtained regioselectively from the reaction of 4,5,6-triaminopyrimidine 1 with 1equiv of methylenedioxychalcones 2a-f and 3a-f, under microwave irradiation. Detailed NMR measurements confirm the high regioselectivity of this reaction. These compounds have been evaluated in the US National Cancer Institute (NCI) for their ability to inhibit approximately 60 different human tumor cell lines, where 4e, 5a and 5b presented remarkable activity against 47, 11 and 37 cancer cell lines, respectively, with the most important GI50 values ranging from 0.068 to 0.35 microM, in vitro assay.
在微波辐射下，通过4,5,6-三氨基嘧啶1与1当量的亚甲基二氧基查耳酮2a-f和3a-f反应，区域选择性地得到了一系列新的外消旋4-氨基-6-芳基-8-(1,3-苯并二氧杂环戊烯-5-基)-8,9-二氢-7H-嘧啶并[4,5-b][1,4]二氮杂䓬4a-f和4-氨基-8-芳基-6-(1,3-苯并二氧杂环戊烯-5-基)-8,9-二氢-7H-嘧啶并[4,5-b][1,4]二氮杂䓬5a-f。详细的核磁共振测量证实了该反应的高区域选择性。这些化合物已在美国国立癌症研究所（NCI）评估了它们抑制约60种不同人类肿瘤细胞系的能力，其中4e、5a和5b分别对47、11和37种癌细胞系表现出显著活性，并在体外试验中，最重要的GI50值范围为0.068至0.35微摩尔。
