FIELD: biochemistry.
SUBSTANCE: invention relates to new isomeric forms of cyclobutyl (S)-2-[[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1 and its pharmaceutically acceptable salts, which have an antiviral effect and can be used in treating hepatitis B, HIV infection. Compounds possess high pharmacokinetic parameters of metabolism, high antiviral activity and selectivity superior to that of the currently used analogs. Cyclobutyl (S)-2-[[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate corresponds to formula 1 
. Preferably, the said compound is cyclobutyl (S)-2-[(S)-[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1.1 or cyclobutyl (S)-2-[(R)-[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1.2 and pharmaceutically acceptable salts thereof
. Preferred salts are cyclobutyl fumarate (S)-2-[(S)-[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1.1.1; cyclobutyl hemifumarate (S)-2-[(S)-[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1.1.2; cyclobutyl hydrochloride (S)-2-[(S)-[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1.1.3; cyclobutyl fumarate (S)-2-[(R)-[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1.2.1; hemifumarate; cyclobutyl (S)-2-[(R)-[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1.2.2; or cyclobutyl hydrochloride (S)-2-[(R)-[[(R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate of formula 1.2.3; structural formulas of these compounds are indicated in the claims. Invention also relates to a method for preparing the compounds of formulas 1, 1.1 and 1.2 and their fumarates, hemifumarates, hydrochlorides by the reaction of cyclobutyl L-alanine ester of formula (2) and the compound of the formula 3 
.
If necessary, the compounds of formula 1 are separated into corresponding stereoisomers 1.1 and 1.2 with optional treating the resulting compounds 1.1 or 1.2 with an appropriate acid.
EFFECT: compounds have an antiviral effect and can be used in treating hepatitis B, HIV infection.
10 cl, 6 ex, 2 tbl
