Novinson T, Okabe T, Robins R K, Matthews T R
J Med Chem. 1976 Apr;19(4):517-20. doi: 10.1021/jm00226a014.
A general method for the preparation of substituted azolo-as-triazines is reported. The various alpha-aminoazoles (3-aminopyrazole, 3-amino-s-triazole, 5-amino-v-triazole, 2-aminoimidazole, 4(5)-aminoimidazole, and their substituted derivatives) were diazotized and coupled with active methylene reagents (beta-diketones, beta-keto esters, beta-keto acids, ethyl cyanoacetate and malononitrile) to afford intermediates which were then cyclized in methanol, acetic acid, or benzene. The cyclized products were the corresponding pyrazolo[2,3-c]- (2), s-triazolo[2,3-c]- (3), imidazo[3,4-c]- (4), v-triazolo[1,2-c]- (5), and imidazo[3,4-c]-as-triazines (6) with substituents such as amino, alkyl (or hydrogen), ester, ketone, or nitrile, depending on the methylene reagent used. Of the 28 compounds synthesized (representative of the five heterocycles) six, with various substituents, exhibited specific in vitro antimicrobial activity. Compounds 2b and 2d inhibited the gram-negative bacterium Pseudomonas, 3a, and 5a inhibited the gram-positive Staphylococcus, 2h inhibited the dermatophyte Trichophyton, and 2c inhibited the yeast Candida in the MIC (minimum inhibitory concentration) range of 0.40-0.16 mumol/ml.
报道了一种制备取代唑并[3,4 - c][1,2,4]三嗪的通用方法。各种α-氨基唑（3-氨基吡唑、3-氨基-s-三唑、5-氨基-v-三唑、2-氨基咪唑、4(5)-氨基咪唑及其取代衍生物）经重氮化后与活性亚甲基试剂（β-二酮、β-酮酯、β-酮酸、氰基乙酸乙酯和丙二腈）偶联，得到中间体，然后在甲醇、乙酸或苯中进行环化。环化产物是相应的吡唑并[2,3 - c]-（2）、s-三唑并[2,3 - c]-（3）、咪唑并[3,4 - c]-（4）、v-三唑并[1,2 - c]-（5）和咪唑并[3,4 - c][1,2,4]三嗪（6），其取代基如氨基、烷基（或氢）、酯、酮或腈，取决于所使用的亚甲基试剂。在合成的28种化合物（代表5种杂环）中，有6种具有不同取代基的化合物表现出特定的体外抗菌活性。化合物2b和2d抑制革兰氏阴性菌铜绿假单胞菌，3a和5a抑制革兰氏阳性菌金黄色葡萄球菌，2h抑制皮肤癣菌毛癣菌，2c在0.40 - 0.16μmol/ml的最低抑菌浓度（MIC）范围内抑制酵母白色念珠菌。
