Structure Modification Of Helicid And Their Hypnotic-Sedative Activity Research

Structure modification to lead compounds existed in the nature is an important means of innovation new drugs in order to improve bioavailability. Helicid(4-formy- lphenl-β-D-Allopyranoside) was extracted from the fruits of plant Helicia Erratica Hook which was widely distributed in Yunnan Province. It was used safely and had good hypnotic-sedative activity, particularly in the treatment of neurasthenia and vascular headache. Helicid Tablets was used in clinic over twenty years.Many animal experiments and clinical studies suggested that the important reason for poor oral absorption and low bioavailability may be the low oil-solubility and its unique pharmacokinetics,and it was seriously hampered widely used in clinic. Therefore, helicid was chosen as a lead compounds.Through its structure modification,helicid derivatives were designed and synthesized by increase oil-solublility or adjustment parameters of pharmacokinetic in order to improve bioavailability.This is significant to helicid widely used in clinic.Up to now,there is no report of structure modification to helicid.According to the reason of low bioavailability,helicid was used as starting material,we designed and synthesized eighteen helicid derivatives,and the structures of all these new compounds were confirmed by HNMR,MS,HRMS and IR.1)Seven novel [α-(2-oxoalkyl)-α-(substituted anilimo) methy] phenylβ-D-allop- yranoside derivatives were designed and synthesized by the Mannich reaction with substituted aniline and aliphatic ketone.2)Six novel 4-substituted methyl phenyl-β-D-allopyranoside derivatives were designed and synthesized by the Schimdt-Claisen condensation of the aldehyde...