1.含有腙键的嘧啶并三氮唑类化合物,其特征在于,具有通式I所示结构:
R1为C1-5烷基,炔丙基,烯丙基,苄基;
R2为氢,C1-5烷基,羟基取代的C1-5烷基,被不饱和五元杂环取代的C1-3烷基,苯基,苄基,卤代苯基,卤代苄基,羟基取代的苄基;
R3为苯基,吡啶基,萘基,噻吩基,呋喃基,吲哚基,卤代苯基,被C1-5烷基取代的苯基,被硝基取代的苯基,被甲氧基取代的苯基,被羟基取代的苯基,被C1-3烷基氨基取代的苯基,被羟基取代的萘基;
R4为氢,C1-5烷基。
2.如权利要求1所述的含有腙键的嘧啶并三氮唑类化合物,其特征在于,选如下取代基:
R1为甲基,丙基,苄基,炔丙基,烯丙基;
R2为苄基,甲基,羟乙基,被噻吩取代的甲基,被呋喃取代的乙基,单卤代苄基,羟基单取代的苄基;
R3为苯,萘基,吡啶基,噻吩基,吲哚基,羟基单取代的萘基,单卤代苯基,被甲基单取代的苯基,被硝基单取代的苯基,被甲氧基取代的苯基,被羟基单取代的苯基,被二甲基氨基单取代的苯基;
R4为氢,甲基;
所述卤素选氟、氯或溴。
3.如权利要求1所述的含有腙键的嘧啶并三氮唑类化合物,其特征在于,优选如下化合物之一:
9:R1 = Propyl-;R2 = Bn-;R3 =Ph-;R4=H-;
10:R1 = Propyl-;R2 = Bn-;R3 =2-Cl-Ph-;R4=H-;
11:R1 = Propyl-;R2 = Bn-;R3 =3-Cl-Ph-;R4=H-;
12:R1 = Propyl-;R2 = Bn-;R3 =4-Cl-Ph-;R4=H-;
13:R1 = Propyl-;R2 = Bn-;R3 =4-Br-Ph-;R4=H-;
14:R1 = Propyl-;R2 = Bn-;R3 =2-F-Ph-;R4=H-;
15:R1 = Propyl-;R2 = Bn-;R3 =4-Me-Ph-;R4=H-;
16:R1 = Propyl-;R2 = Bn-;R3 =3,4,5-triMeO-Ph-;R4=H-;
17:R1 = Propyl-;R2 = Bn-;R3 =4-NO2-Ph-;R4=H-;
18:R1 = Propyl-;R2 = Bn-;R3 =4-(N,N-diMe)-Ph-;R4=H-;
19:R1 = Propyl-;R2 = Bn-;R3=;R4=H-;
20:R1 = Propyl-;R2 = Bn-;R3=;R4=H-;
21:R1 = Propyl-;R2 = Bn-;R3=;R4=H-;
22:R1 = Propyl-;R2 = Bn-;R3=;R4=H-;
23: R1 = Propyl-;R2 = Bn-;R3=;R4=H-;
24: R1 = Propyl-;R2 = Bn-;R3 =Ph-;R4=CH3-;
25: R1 = Propyl-;R2 = Bn-;R3 =4-MeO-Ph-;R4=CH3-;
26: R1 = Propyl-;R2 = Bn-;R3 =2-OH-Ph-;R4=CH3-;
27: R1 = Propyl-;R2 = Bn-;R3 =4-OH-Ph-;R4=CH3-;
28: R1 = Propyl-;R2 = Bn-;R3 =4-Br-Ph-;R4=CH3-;
29: R1 = Propyl-;R2 = ;R3 =2-OH-Ph-;R4=CH3-;
30:R1 = Propyl-;R2 =2-Cl-Bn-;R3 =2-OH-Ph-;R4=CH3-;
31:R1 = Propyl-;R2 =3-Cl-Bn-;R3 =2-OH-Ph-;R4=CH3-;
32:R1 = Propyl-;R2 =4-Cl-Bn-;R3 =2-OH-Ph-;R4=CH3-;
33:R1 = Propyl-;R2 =4-Br-Bn-;R3 =2-OH-Ph-;R4=CH3-;
34:R1 = Propyl-;R2 =4-F-Bn-;R3 =2-OH-Ph-;R4=CH3-;
35:R1 = Propyl-;R2 =;R3 =2-OH-Ph-;R4=CH3-;
36:R1 = Propyl-;R2 =;R3 =2-OH-Ph-;R4=CH3-;
37:R1 = Propyl-;R2 =4-OH-Bn-;R3 =2-OH-Ph-;R4=CH3-;
38:R1 = Propargyl-;R2 =Bn-;R3 =3,4,5-triMeO-Ph-;R4=H-;
39:R1 = Propargyl-;R2 =Bn-;R3=;R4=H-;
40:R1 = Propargyl-;R2 =Bn-;R3 =4-(N,N-diMe)-Ph-;R4=H-;
41:R1 = Propargyl-;R2 =Bn-;R3 =2-OH-Ph-;R4= CH3-;
42:R1 = Bn-;R2 =Bn-;R3 =3,4,5-triMeO-Ph-;R4= H-;
43:R1 = Bn-;R2 =Bn-;R3 =2-OH-Ph-;R4= CH3-。
4.如权利要求1-3其中之一所述的含有腙键的嘧啶并三氮唑类化合物在制备药物中的应用,其特征在于,将其做为活性成分用于制备抗肿瘤药物。
5.制备如权利要求1或2所述的含有腙键的嘧啶并三氮唑类化合物的方法,其特征在于,包括以下步骤:
通式2a~c的制备方法:
溶剂中,将化合物1和溴代烃,在碱性物质作用下,搅拌加热反应,有沉淀生成,过滤,洗涤,干燥,得化合物2a~c;所用溶剂选丙酮、甲醇、乙醇、丙醇、异丙醇、四氢呋喃、乙腈、水、DMF、二氯甲烷、氯仿、二氧六环中之一或者其中任意或三种的混合物;所用碱性物质选三乙胺、二异丙基乙胺、吡啶、氢氧化钠、氢氧化钾中的一种;
通式3a~c的制备方法:
在醋酸中,加入硝化试剂,然后分批加入化合物2a~c,搅拌,然后倒入水中,抽滤,洗涤,干燥,得化合物3a~c;所述硝化试剂选发烟硝酸,浓硝酸;
(3).通式4a~c的制备方法:
室温下,溶剂中,加入氯化试剂,分批加入化合物3a~c,然后滴加有机碱,回流反应,冷至室温,水解,用有机溶剂萃取,水洗,中和,干燥有机相即得化合物4a~c粗品;所述氯化试剂选三氯氧磷,五氯化磷;所述溶剂选甲苯,二氧六环,THF,乙酸乙酯;所述有机碱选三乙胺、N,N-二甲基苯胺、N,N-二乙基苯胺或吡啶;
(4).通式5a~c的制备方法:
将化合物4a~c溶于乙醇和醋酸的混合溶剂中,然后分批加入还原铁粉,加热反应,结束后,抽滤,旋干溶剂,再用有机溶剂萃取,水洗,干燥有机相,即得到化合物5a~c的粗品;
(5).通式6a~l的制备方法:
将化合物5a~c和胺类化合物溶于溶剂中,再加入有机碱,回流反应,结束后蒸干溶剂,加入乙酸乙酯,水洗,干燥有机相,即得到化合物6a~l的粗品;所用溶剂选甲醇,乙醇,异丙醇,DMF,二氧六环,THF,乙腈;所述有机碱选三乙胺,吡啶或二异丙基乙胺;所述胺类化合物与R2取代基对应;
(6).通式7a~l的制备方法:
将化合物6a~l溶于醋酸和水的混合液中,滴加亚硝酸钠的水溶液反应,加入乙酸乙酯和水,分层,水洗数次,用碳酸钠中和,干燥有机相,即得化合物7a~l粗品;
(8).通式8a~l的制备方法:
将化合物7a~l溶于乙醇中,然后加入水合肼,搅拌反应,抽滤即得化合物8a~l,干燥;
(9).通式I的制备方法:
将化合物8a~l和醛或酮溶于溶剂中,加入醋酸,回流反应,冷却至室温,抽滤得粗品,根据纯度再进行重结晶得到最终产品;所述溶剂选甲醇,乙醇,异丙醇,THF,乙腈。