Structure Modification Of Helicid And Their Hypnotic-Sedative Activity Research (â…¡)

Structure modification to lead compounds existed in the nature is an important means of innovation new drugs in order to improve biologic activity and to reduce bad effect. 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, low bioavailability and slow effect may be the low oil-solubility and its unique pharmacokinetics, and it was seriously hampered widely used in clinic. In previous work of helicid's structure modification show that 4 substituted groups of helicid are some ordinary acyclic and substituted aniline group, and it had no heptad heterocyclic substituted group. Therefore, we are based upon our previous work, 1,5- benzothiazepine that have good biologic activity was joined in helicid for studying thorough structure and activity relationship of the compounds. And then novel helicid derivatives were synthesized. This work is significant to filter and empolder novel drugs with good hypnotic-sedative activity. helicid was used as starting material, we designed and synthesized ten helicid derivatives, and the structures of all these new compounds were confirmed by 1HNMR,MS,HRMS and IR.1)Five novel E-(4-β-D-allopyranosyloxyphenyl)-1-(4-substituted phenyl) propenone derivatives were designed and synthesized by the Claisen-Schimidt reaction with 4-substituted hypnone.2)Five novel 2-(4-β-D-allopyranosyloxyphenyl)-4-aryl-2,3-dihydro-1,5- benzo- -thiazepine derivatives were designed and synthesized by the 1,4-Michael reaction with E-(4-β-D-allopyranosyloxyphenyl)-1-(4-substituted phenyl) propenone derivatives.3)2-(4-β-D- allopyranosyloxyphenyl)-4-aryl-2,3-dihydro-1,5-benzothiazepine derivatives had hypnotic-sedative acitivity test. The preliminary bioassay test suggested that many of such compounds should show good calm activity. And all compounds showed the better activity than the parent helicid. They are worth to study in further, and gradually developed into a new generation of practical hypnotic-sedative drugs.The results of this research papers can help us to find a better hypnotic-sedative drug in future.