摘要
为寻找强效无成瘾性的镇痛药，在已知某些硫乙内酰脲衍生物（ＰＴＨ－ＡＡ）的镇痛作用与脑啡肽酶抑制关系的认识基础上，以ＤＬ－氨基酸与硫代异氰酸苯酯为原料合成了２５个ＰＴＨ－ＡＡ衍生物：（±）５－氨基酸残基－３－取代苯基－２－硫代乙内酰脲。经小白鼠热板试验发现，ｐ－ＥｔＯＯＣＰＴＨ－Ａｌａ（ＹＬ－２），ｍ－ＥｔＯＯＣ－ＰＴＨ－Ｐｈｇ（ＹＬ－１２），ｍ－ＥｔＯＯＣ－ＰＴＨ－Ａｌａ（ＹＬ－１３）（５０ｍｇ／ｋｇ，ｉｐ）具有较强镇痛作用，与盐酸吗啡（２０ｍｇ／ｋｇ，ｉｐ）相当。
For the purpose of searching for new potent analgesics,a series of thiohydantoin derivaTives,(±)5-amino acid residue-3-substituted-phenyl-2-thioxo-hydantoins(substituted-PTH-AA)were designed based on to the inhibitory mechanism of enkephalinase and synthesized with DL-amino acids and corresponding substituted-phenyl isothiocyanates.Studies on the antinociceptive activity were extended to these 25 newly synthesized thiohydantoin derivatives.The mouse hot plate test(in vivo)showed that the antinociceptive activity of p-EtOOC-PTH-Ala(YL-2 ),m-EtOOC-PTH-Ala(YL-12),m-EtOOC-PTH-Phg(YL-13)(50 mg/kg,ip)might be compared with that of morphine hydrochloride(20 mg/kg,ip).
出处
《中国药科大学学报》
CAS
CSCD
北大核心
1995年第5期257-262,共6页
Journal of China Pharmaceutical University
基金
国家自然科学基金
关键词
硫乙内酰脲
衍生物
脑啡肽酶抑制剂
镇痛药
合成
Enkephalinase
Enkephalinase inhibitor
Amino acid
Thiohvdantoin derivative
Antinoci-ceptive activity
