4,6-二芳基-2-氨基嘧啶类衍生物的合成与生物活性

Synthesis and Biological Activities of 4,6-Diaryl-2-aminopyrimidine Derivatives

合成并表征了5种4,6-二芳基-2-氨基嘧啶类化合物。测试了它们对大肠肝菌甲硫酰胺肽酶（EcMetAP）的抑制作用及对CXCR4受体的拮抗作用。发现5种化合物均对EcMetAP酶活有抑制作用,除化合物2外均对CXCR4受体有拮抗作用。利用FieldTemplater和FieldAlign软件对化合物1~5的上述活性构效关系进行了分析,初步认为化合物的嘧啶环3位N原子及4位取代苯环上若引入给电子基团,可增强这类化合物的EcMetAP酶抑制活性;在嘧啶环2位引入负电性较强的基团取代,改造2个苯环和嘧啶环的4、5、6位C原子的结构可增强其CXCR4受体拮抗活性。

Five kinds of 4,6-diaryl-2-aminopyrimidine derivatives were synthesized and characterized by IR,MS and 1H NMR.The Escherichia coli methionine aminopeptidase（EcMetAP） inhibit-activities and the CXCR4 receptor antogonists activities of the five compounds were determined.The results show that all the five compounds have the EcMetAP inhibit-activities,and they also have CXCR4 receptor antogonists activities except the compound 2.The structure-activity relationships were studied by the FieldTemplater and FieldAlign software through molecular field analysis.The results show that the pharmacophore could be 3-N atom and 4,6-bencycles used as the EcMetAP inhibitor,and the EcMetAP inhibit-activities could be increased by addition of electron-donating groups at 6-benzyl.It also shows that the pharmacophore could be 2-C atom and 4,6-bencycles used as the CXCR4 receptor antogonists.The CXCR4 receptor antogonists could be increased by addition of electron-donating substituent at 2-C.