Abstract: In order to get some selective κ-opioid receptor agonists, which can relieve pain while lackingserious side effects, 16 target compounds of hexahydro-1H-1, 4-diazepine analogues carrying the segmentof (1-arylacetamide-2-tertiary amide) ethane were synthesized through single amidation and amidation ofthe basic modified structures of compounds 1-3, 2-(5-) substituted hexahydro-1H-1, 4-diazepine.Thestructures of these products were characterized by IR, EIMS, elementary analysis and ¹H NMR.All thetarget compounds were screened in vitro in the guinea pig ileum(GPI) for their receptor affinities.The pre-liminary pharmacology tests indicated that these compounds showed a certain agonist activity(presented inthe item of inhibition rate) respectively at 5 × 10^-6mol/Llevel and the IC₅₀ values(μmol/L) of compounds5, 7 were achieved.The antinociceptive potencies of the compounds with a higher potency(compounds 5,13, 22, 23) in the GPIstudy were further tested their in the mouse abdominal constriction model and their ED₅₀ values(mg/kg, s.c.) were also obtained.

Key words: Selective κ-opioid receptor agonists, Analgesic effect, Hexahydro-1H-1, 4-diazepine ana-logues, (1-Arylacetamide-2-tertiary amide) ethane structure