Temple C, Rener G A
Southern Research Institute, Birmingham, Alabama 35255-5305.
J Med Chem. 1990 Nov;33(11):3044-50. doi: 10.1021/jm00173a021.
Ring analogues and derivatives of the 1,2-dihydropyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 29), antimitotic agents with antitumor activity, were prepared in the search for compounds with greater selectivity. Methods were developed for the conversion of substituted benzoic acids (1-4) to give benzopyrazines (12-16 and 21) and of substituted pyridin-2-carbamates (23, 38, and 41) to give 2-aminopyrido[3,4-b]pyrazin-7-ylcarbamates (32 and 36) and pyrido[3,4-e]-as-triazin-7-ylcarbamates (47 and 50). In vitro evaluation indicated that activity was reduced by removal of the pyridine ring nitrogen of 29 to give 14 and was destroyed by increasing the basicity of the pyrazine ring of 29 to give 32 and 47.
1,2 - 二氢吡啶并[3,4 - b]吡嗪 - 7 - 基氨基甲酸酯类（如29）的环状类似物和衍生物是具有抗肿瘤活性的抗有丝分裂剂，它们是在寻找具有更高选择性的化合物过程中制备的。已开发出将取代苯甲酸（1 - 4）转化为苯并吡嗪（12 - 16和21）以及将取代吡啶 - 2 - 氨基甲酸酯（23、38和41）转化为2 - 氨基吡啶并[3,4 - b]吡嗪 - 7 - 基氨基甲酸酯（32和36）以及吡啶并[3,4 - e] - 1,2,4 - 三嗪 - 7 - 基氨基甲酸酯（47和50）的方法。体外评估表明，通过去除29的吡啶环氮得到14会降低活性，而通过增加29的吡嗪环碱性得到32和47会破坏活性。
