摘要
在已知某些硫乙内酰脲(PTH-AA)的镇痛作用与脑啡肽酶抑制关系的认识基础上,以DL-氨基酸和含氟取代硫代异氰酸苯酯为原料,合成了17个硫乙内酰脲衍生物:(±)5-氨基酸残基-3-取代苯基-2-硫代-乙内酰脲(简称取代-PTH-AA)。经小白鼠热板试验发现,3-CF_3-PTH-Ala(YZ_1)(100 mg/kg,ip)、3-Cl-4-F-PTH-Ala(YZ_8)(100 mg/kg,ip)和3-Cl-4-F-PTH-Arg-HCl(YZ_(15)(100 mg/kg,ip)具有较强的镇痛作用,与盐酸吗啡(40 mg/kg,ip)相当。
On the basis that the antinociceptive activity of some phenyl-thiohydantoin (PTH) compounds was due to the inhibition of enkephalinase, a series of amino acid derivatives (±) 5-amino acid residue-3-substitutedphenyl-2-thioxo-hydantoins (substituted-PTH-AA) were designed and synthesized in order to find novel potent analgesics. Studies on the antinociceptive activity were extended to these 17 newly synthesized thiohydantoin derivatives. The mouse hot plate test (in vivo) showed that the antinociceptive activity of 3-CF_3-PTH-Ala (YZ_1) (100 mg/kg, ip), 3-Cl-4-F-PTH-Ala (YZ_8) (100 mg/kg, ip)and 3-Cl-4-F-PTH-Arg HCl (YZ_(15)) (100 mg/kg, ip) might be compared with that of morphine hydrochloride (40 mg/kg, ip).
出处
《中国药科大学学报》
CAS
CSCD
北大核心
1991年第6期330-333,共4页
Journal of China Pharmaceutical University
关键词
硫乙内酰脲
衍生物
合成
止痛
Enkephalinase
Enkephalinase inhibitors
Amino acids
Thiohydantoin derivatives
Antinociceptive activity
