Design And Synthesis Of Ethyl 5 - Hydroxy - 1H - Indole - 3 - Carboxylic Acid Ethyl Esters

The biological characteristic of hepatitis B virus and mechanism of anti-hepatitis B virus drugs were introduced briefly and the recent advances of nucleoside and non-nucleoside anti-HBV drugs were described in detail in the paper. Particularly, the design and synthesis of ethyl 5-hydroxy-lH-indole-3-carboxylate derivatives were researched.Previously, we have obtained a series of ethyl 5-hydroxy-lH-indole-3-carboxylate derivatives with the abilities to inhibit the replication of HBV in vitro. Based on the research of structure-activity relationship (SAR) between the modification of substituents on the indole cycle and anti-HBV activity, the modifications were focused on1,2,4-position of indole ring to find better anti-hepatitis B virus compands and perfect the S AR of 5-hydroxy-1H-indole-3-carboxy-late derivatives. For 1-position, methyl or cyclopropyl were introduced; For 2-position, cycloalkane, substituted thiazolyl etc. were introduced; For 4-position, different amino-group were introduced.Taking ethyl acetoacetate as starting material, through a series of reaction as follow: condensation reaction, nenitzescu cyclization, esterification, bromine reaction, mannich reaction, amine exchange reaction, single oxidation or double oxidation reaction of thionic, a new synthetic scheme was developed and 19 target compounds which had not been reported in literatures were synthesized. The structures of the target compounds were confirmed by MS and 1H-NMR.