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根据氨基喹唑啉类化合物抑制叶酸代谢的机理及其构效关系,设计合成了以下三类喹唑啉化合物:Ⅰ,5-氯(氟)-2,4-二氨基-6-(取代苄基氨基)喹唑啉;Ⅱ,5-氯(氟)-2,4-二氨基-6-(N-甲酰-N-取代苄基氨基)-喹唑啉;Ⅲ,5-氯-2,4-二氨基-6-(N-亚硝基-N-取代苄基)氨基喹唑啉。所合成的18个化合物均为未知物,经元素和光谱分析确证其结构。化合物Ⅰ_(1～8)的合成采用5-氯(氟)-2,4, 6-三氨基喹唑啉(8,14)与取代苯甲醛缩合、还原而得,Ⅰ经甲酰化或亚硝化分别得到Ⅱ_(1～6)和Ⅲ_(1～4)。8的合成是将间氯苯胺与三氯乙醛、盐酸羟胺反应,得到的1-(α-肟基乙酰)3-氯苯胺(2)经环合后分除异构体得4-氯靛红(3a),3a经肟化、开环得到2-氨基-6-氯苄腈(5),5再与氰胺环合、硝化、还原即得8。14的合成尚未见报道。我们将5重氮化、氯化,再氟化制得2,6-二氟苄腈(10),10经氨化、环合得
According to the mechanism of amino-quinazoline inhibition of folic acid metabolism and its structure-activity relationship, the following three quinazoline compounds were designed and synthesized: Ⅰ, 5-chloro-fluoro-2,4-diamino-6- Amino) quinazoline; II. 5-chloro-fluoro-2,4-diamino-6- (N-formyl-N-substituted benzylamino) , 4-diamino-6- (N-nitroso-N-substituted benzyl) aminoquinazoline. All the 18 compounds synthesized were unknown, and their structures were confirmed by elemental and spectral analysis. The synthesis of compound Ⅰ_ (1 ~ 8) was synthesized by the condensation of 5-chloro (fluoro) -2,4,6-triaminoquinazoline (8,14) with substituted benzaldehyde, The nitration obtained Ⅱ_ (1-6) and Ⅲ_ (1-4) respectively. The synthesis of 8 is the reaction of m-chloroaniline with trichloroacetaldehyde and hydroxylamine hydrochloride to give the 1- (α-oximinoacetyl) 3-chloroaniline (2) (3a), 3a oximation, ring-open to give 2-amino-6-chlorobenzonitrile (5), 5 and then Cyanamidocyclyl, nitration, the reduction obtained 8.14 synthesis has not been reported. We will 5 diazotization, chlorination, re-fluorination of 2,6-difluorobenzonitrile (10), 10 by ammoniation, cyclization was