1-(取代萘基-2)-1,2-二氢-2,2-二甲基-4,6-二氨基-1,3,5-三嗪的合成及结构与抗癌活性的关系

SYNTHESIS AND STRUCTURE-ANTITUMOR ACTIVITY OF 4,6-DIAMINO-1, 2-DIHYDRO-2, 2-DIMFTHYL-1-(SUBSTITUTED NAPHTHYL-2)-1,3,5-TRIAZINES

按Modest方法合成了11个新的1-(取代萘基-2)-1,2-二氢-2,2-二甲基-4,6-二氨基-1,3,5-三嗪(Ⅴ)。用于合成三嗪的取代-2-萘胺(Ⅵ),也一并在本文中报道。以人早幼粒白血病细胞HL—60测定了(Ⅴ)的抗癌活性。定量构效关系研究表明,(Ⅴ)的抗癌活性与6-取代基的立体参数(MR)呈负相关关系。推测可能是刚性的萘环6-位取代基不为二氢叶酸还原酶的活性空间所容纳的缘故。

Eleven new 4,6-diamino-1,2-dihydro-2,2-dirfiethyl-1-(substituted naphthyl-2)-1,3,5-triazines(v)were synthesized according to the Modest's method.The corresponding substituted 2-naphthylamines(Ⅵ) used for the synthesis of triazines was also reported in this paper.The antitumor activity of(Ⅴ)was tested by using the human promyelocytic leukemia cell line HL-60.The quantitative structure-activity relationship studies showed that the activity negatively correlated with the molecular refractivity(MR,stands for steric parameter) Of 6-substituents.It was inferred that the substituents at the 6th position of the rigid bulky naphthyl moiety could not fit the pocket of the aetive-site of dihydrofolate reductase of HL-60 cell.