2, 6-Dinitrogen-Containing Substituted Purine Derivatives, The Preparation And Uses Thereof

Compounds of formula (A) or salts or solvates thereof or the solvates of salts thereof:

• wherein:
• W represents an optionally monosubstituted C1˜C6 straight or branched alkylamino, an optionally monosubstituted C3˜C6 straight or branched alkenyl or alkynyl amino, an optionally disubstituted C1˜C6 straight or branched alkylamino, an optionally disubstituted C3˜C6 straight or branched alkenyl or alkynyl amino, cyclopropylamino, cyclobutylamino;
• W may also represent amino substituted by two different C1˜C6 straight or branched alkane, or represent amino substituted by two different C3˜C6 straight or branched olefin, or amino which one end is substituted by C1˜C6 alkane and the other end is substituted by C3˜C6 olefin, or an optionally substituted pyrrolidine, piperidine, morphine or piperazidine;
• the substituent represents C1˜C6 straight or branched alkyl or halogen or hydroxyl;
• Y represents H or a pharmaceutically acceptable saccharide, wherein the saccharide represents any one of the following formulas:
• Z represents H or any one of the following formulas:
• Q represents any one of the following formulas:
• in the above formulas, B, E, G, R, T, M each independently represents a H or a C1˜C6 straight or branched alkyl, or haloalkyl, a C3˜C6 cycloalkyl, halogen, CN, NH2, methoxyl, ethyoxyl or nitro;
• with the exception of the following compounds:
• W represents cyclopropylamino or cyclobutylamino, Y represents H or an above-mentioned pharmaceutically acceptable saccharide, Q represents any one of the following formulas:
• wherein B, E, G, R, T, M simultaneously represents H.

A method for preparing the compounds of formula (A) or salts or solvates thereof or the solvates of salts thereof, wherein the method includes the following steps:

• 1) firstly reacting the compound (a) with 2,3-dihydropyrane under catalysis of catalysts such as paratoluenesulfonic acid or pyridinium salt of paratoluenesulfonic acid;
• and then in the presence of depickling solvent such as triethylamine, sodium carbonate, potassium carbonate or sodium bicarbonate, condensating with W at a condensation reaction temperature of 20˜100° C. to obtain compound (b);
• 2) in the presence of catalysts, bases and aprotic solvents, undergoing catalytic coupling reaction and deprotecting and salt-forming reaction of deprotecting group of compound (b) and Q-NH2 at a catalytic coupling reaction temperature of 15˜150° C., to obtain compound (d);
• wherein, in the catalytic coupling reaction, the ligand includes tri-o-tolylphosphine, tri-tert-butylphosphine, 2,2′-diphenylphosphine-1,1′-binaphthalene, 1,1′-diphenylphosphine-ferrocene, bis(2-diphenylphosphinophenyl)ether, 9,9-dimethyl-4,5-diphenylphosphine xanthene, or the ligand is the compounds of formula 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
• the catalyst is a transition metal catalyst of palladium or nickel such as PdCl2, Pd(OAc)2, Pd2(dba)3, Ni(OAc)2, or Ni/C;
• the base is sodium tert-butoxide, potassium tert-butoxide, potassium carbonate, cesium carbonate or tripotassium phosphate;
• the deprotecting and salt-forming reaction could be carried out under the acidic condition such as hydrochloric acid, sulphuric acid, hydrobromic acid, methanesulfonic acid, benzene sulfonic acid, paratoluenesulfonic acid, maleic acid, fumaric acid, lactic acid or citric acid;
• 3) neutralizing compound (d) with sodium carbonate, potassium carbonate, sodium hydroxide, or potassium hydroxide to obtain compound (e),
• wherein:
• W represents an optionally monosubstituted C1˜C6 straight or branched alkylamino, an optionally monosubstituted C3˜C6 straight or branched alkenyl or alkynyl amino, an optionally disubstituted C1˜C6 straight or branched alkylamino, an optionally disubstituted C3˜C6 straight or branched alkenyl or alkynyl amino, cyclopropylamino, cyclobutylamino;
• W may also represent amino substituted by two different C1˜C6 straight or branched alkane, or represent amino substituted by two different C3˜C6 straight or branched olefin, or amino which one end is substituted by C1˜C6 alkane and the other end is substituted by C3˜C6 olefin, or an optionally substituted heterocycle pyrrolidine, piperidine, morphine or piperazidine;
• the substituent represents C1˜C6 straight or branched alkyl or halogen or hydroxyl;
• Y represents H or a pharmaceutically acceptable saccharide, wherein the saccharide represents any one of the following formulas:
• Z represents H or any one of the following formulas:
• Q represents any one of the following formulas:
• in the above formulas, B, E, G, R, T, M each independently represents a H or a C1˜C6 straight or branched alkyl, or haloalkyl, a C3˜C6 cycloalkyl, halogen, CN, NH2 methoxyl, ethyoxyl or nitro;
• with the exception of the following compounds:
• W represents cyclopropylamino or cyclobutylamino, Y represents H or an above-mentioned pharmaceutically acceptable saccharide, Q represents the compounds of any one of the following formulas:
• wherein B, E, G, R, T, M simultaneously represents H.