Benzohetercyclic compounds, preparation method thereof and applications thereof
The invention provides non-nucleoside antiviral inhibitors, especially benzohetercyclic compounds shown by a general formula I or pharmaceutically acceptable salts thereof or hydrates thereof. The invention further provides a method for preparing the compounds or the pharmaceutically acceptable salts thereof or the hydrates thereof. Pharmacological tests show that the compounds or the pharmaceutically acceptable salts thereof or the hydrates thereof can effectively inhibit replication of hepatitis B virus DNA and hepatitis C virus RNA. Therefore, the invention further provides applications of the compounds in preparation of medicaments preventing and/or treating viral infection, especially the hepatitis B virus (HBV) infection and the hepatitis C virus (HCV) infection. 1. A kind of the general formula I shown as benzo heterocyclic compound or its pharmaceutically acceptable salt or hydrate thereof: N X is; N= 1-10; R1 and R3 are respectively independently represent H, a halogen atom, R, -CH2 R, -NO2, -CN, -NH2, -NHR, -NRR ',-NHCOR, -NHCOCH (R' ') NH2, -NHSO2 R, -OH, -OR, -OCOR, -OCOCH (R' ')NH2, -OSO2 R, COOH or COOR; R1 are a single or a plurality of substituents, of the benzene ring respectively 4 bit, 5 bit, 6-bit or 7-bit; R2 to H, R, -CH2 R, -COR, -SO2 R, -CH2 CH2 NRR 'or-CH2 CH2 N (O) RR'; R4 and R5 is independently H, R, -CH2 R, -COR, -COCH (R '') NH2 or-SO2 R; or R4, R5 and forming a N 4-10 membered saturated or unsaturated ring, wherein the saturated or unsaturated ring optionally containing 0-4 selected from N, O and in S the hetero-atom; R6 is O or non-substituted; Wherein R, R ' is the same or different C1-C10 straight-chain or branched chain saturated alkyl, C2-C10 straight-chain or branched chain unsaturated alkenyl, C3-C10 cycloalkyl, phenyl or substituted phenyl, thienyl or substituted thienyl, furyl or substituted furyl, pyridyl or substituted pyridyl; R '' is 20 in the natural L-amino acid the side chain of an amino acid. 2. Benzocarbazoles heterocyclic compound or its pharmaceutically acceptable salt or hydrate according to Claim 1, characterized in that the general formula VIII on the benzimidazole compound that: 3. Benzocarbazoles heterocyclic compound or its pharmaceutically acceptable salt or hydrate according to Claim 2, characterized in that the general formula IX on the benzimidazole compound that: 4. Benzocarbazoles heterocyclic compound or its pharmaceutically acceptable salt or hydrate according to Claim 3, characterized in that R1 and R3 is independently H, a halogen atom, R, -CH2 R, -NO2, -CN, -NH2, -OH, -OR, -OCOR, COOH or COOR, wherein for R C1-C5 straight-chain or branched chain saturated alkyl, C2-C5 straight-chain or branched chain unsaturated alkenyl, C3-C6 cycloalkyl, phenyl or substituted phenyl, thienyl or substituted thienyl, furyl or substituted furyl, pyridyl or substituted pyridyl; R1 is preferably H, a halogen atom, -OH, -OCH3, -OBn, -OAc, -OCOR, COOH or COOR, and R1 to a single substituent, the benzene ring 5 bit; R3 is preferably H, -OH or phenyl; R4 and R5 is independently H, R, -CH2 R, -COR, wherein the R C1-C5 straight-chain or branched chain saturated alkyl, C2-C5 straight-chain or branched chain unsaturated alkenyl, C3-C6 cycloalkyl, phenyl or substituted phenyl, thienyl or substituted thienyl, furyl or substituted furyl, pyridyl or substituted pyridyl, or R4, R5 and forming a N 4-10 membered saturated or unsaturated ring, wherein the saturated or unsaturated ring optionally containing 0-4 selected from N, O and the hetero-atom in S; R4 and R5 is preferably independently respectively H, -CH3, -CH2 CH3, -CH2 CH2 CH3, -CH (CH3)2, -CH2 CH2 CH2 CH3, -CH2 CH (CH3)2, -CH2 CH2 CH (CH3)2, 5. Benzocarbazoles heterocyclic compound or its pharmaceutically acceptable salt or hydrate according to Claim 4, characterized in that R1 and R3 is independently H; R4 and R5 is independently H, R, -CH2 R or-COR, wherein for R C1-C5 straight-chain or branched chain saturated alkyl, C2-C5 straight-chain or branched chain unsaturated alkenyl or C3-C6 cycloalkyl. 6. Benzocarbazoles heterocyclic compound or its pharmaceutically acceptable salt or hydrate according to Claim 3, characterized in that it is selected from one of the following compounds: 7. Benzocarbazoles heterocyclic compound or its pharmaceutically acceptable salt or hydrate of the preparation method according to Claim 1, characterized in that its by the following chemical reaction formula preparation: Chemical equation Reagent and reaction conditions : (a) anhydrous DMF, NaH (60%), the 0 [...] , 30 min, hydrochloride chloroethylamine , KI, the 80 [...] , 3h ; (b) NaOMe, MeOH, RCHO (corresponding ehyde), NaCNBH3, AcOH, room temperature, 2h ; (c) MCPBA, CHCl3, the 0 [...] , 5 min; or H2 O2, EtOH, 60 , 30 min; Or chemical reaction Reagent and reaction conditions : (a) HCl or H3 PO4 or HNO3 or H2 SO4, acetone or isopropanol or ethanol solvent, room temperature, 30 min. wherein X, R, R1, R3, R4, R5 as in claim 1 defined in the. 8. -6 the benzo heterocyclic compound or its pharmaceutically acceptable salt or hydrate thereof in the preparation of the prevention and/or according to Claim 1 for treating hepatitis b virus infection, hepatitis c virus infection is the use of the medicament. 9. A prevention and/or treatment of hepatitis b virus infection, hepatitis c virus infection of the pharmaceutical composition, comprising a therapeutically effective amount of -6 the benzo heterocyclic compound or its pharmaceutically acceptable salt or hydrate thereof as an active ingredient according to Claim 1, and pharmaceutically acceptable adjuvant.