1. Structural Modification And Xanthine Oxidase(XO) Inhibiton Activity Of Mangiferin;2. Synthesis Of The Related Compounds Of Celecoxib

1.Structural modification and XO inhibition activity of MangiferinThe isolation and modification of natural products have been an important way in finding new drugs. Mangiferin is an active natural polyphenolic conpounds isolated from Anemarrhenae asphodebides. Mangiferin has been reported to possess many biological activities, including anti-asthmatic, anti-oxidation, hypoglycemic, renal protection, immunomodulatory, anti-tumor, anti-gout, and so oaTo date, there have been only a few papers to report Mangiferin having anti-gout activity, but many papers reported the similar structure of flavonoids having anti-gout activity. Cos P has already summarized the structure-activity relationship of flavones used as xanthine oxidase inhibitors. Flavanones and Dihydroflavonols, due to their lack of a double bond between C2-C3, can not exhibit the xanthine oxidase inhibition activity. Conversely, flavonoids and flavonols, due to their double bond between C2-C3, can have the xanthine oxidase inhibition activity. In addition, the C5-OH and C7-OH are also important for their xanthine oxidase inhibition activity. Based on this, we utilize the principle of drug molecular design, the Disjunction and the Bioisosteris, to design and synthesize four types of target conpounds.In this part, fifty-eight compounds have been designed and synthesized. Among them there are fifty-five target compounds including fifty of them haven’t been reported in the literatures.. The structures of the target compounds were confirmed by1H-NMR and MS. In addition, all of the target compounds were first tested for the xanthine oxidase inhibition activity and parts of them showed the xanthine oxidase inhibition activity better than allopurinol. The present work will be helpful to the design and development of anti-gout drug.2. Synthesis of the related compounds of celecoxibCelecoxib is the first inhibitor of cyclooxygenase Ⅱ (COX-2), and it is usually utilized to treat osteoarthritis and rheumatoid arthritis. In the synthesis of Celecoxib, Starting from methyl substituted acetophenone, obtaining the key intermediates4,4,4-trifluoro-1-(4-methyl-phenyl)-1,3-butanedione through Claisen condensation with trifluoroacetate, and finally producing the target compound by a cyclization reaction with4-sulfonamidophenylhydrazine hydrochbride. According to the synthesis, twelve related substances may be generated and two of them (5,6) are under control in the35th edition of United States Pharmacopeia. To date, there are no standard related substances of celecoxib in our country, so we synthetize these related substances in order to perform the quality control of celecoxib.Nine target compounds were synthetized and all their purity are more than99%. Their chemical structures of the target compounds were confirmed by1H-NMR and MS. The target compounds can be used as the reference substance to control the Celecoxib quality.