四氢异喹啉衍生的异硫脲类化合物的合成及NOS抑制活性研究

目的设计、合成新的1，2，3，4-四氢异喹啉衍生的异硫脲类化合物，并研究其对NOS抑制活性。方法 将1，2，3，4-四氢异喹啉-2-基引入到异硫脲结构中，测试新合成的目标化合物的NOS抑制活性。结果和结论合成了22个未见文献报道的(烃亚胺基)(1，2，3，4-四氢异喹啉-2-基)甲基烃基硫醚类化合物(I类)和S-烃基-1-苯基-3-［4-(1，2，3，4-四氢异喹啉-2-基)亚甲基］苯基异硫脲类化合物(II类)，结构经IR，¹H NMR，MS及元素分析确证。初步药理筛选结果显示，部分I类目标化合物(I-9和I-13)的NOS抑制活性高于阳性对照样品氨基胍(AG)，而II类化合物的NOS抑制活性均较低。

Synthesis of isothioureas derived from tetrahydroisoquinoline and NOS inhibitory activity

Aim To get some novel potent compounds with NOS inhibitory activity, a series of new compounds of isothioureas derived from 1,2,3,4-tetrahydroisoquinoline were synthesized. Methods 1,2,3,4-Tetrahydroisoquinol-2-yl was introduced into the structure of isothioureas, the NOS inhibitory activity of the new compounds synthesized were measured. Results and Conclusion Twenty-two isothiourea derivatives of alkyl(or aryl)imino] (1,2,3,4-tetrahydroisoquinol-2-yl)methyl alkyl thioethers (I) and S-alkyl-1-phenyl-3-4-(1,2,3,4-tetrahydroisoquinol-2-yl)methane]phenyl isothioureas (II) were synthesized from thioureas by S-alkylation with alkyl halides, and their structures were identified by IR, ~(1)H NMR, MS and elemental analysis. The preliminary biological test showed that the part of type I (I-9 and I-13) had higher NOS inhibitory activity than that the control aminoguanidine (AG), but the type II had weak ability to inhibit NOS.