DERIVATIVE BASED ON DIHYDROPYRIMIDO-RING AS HBV INHIBITOR Russian patent published in 2019 - IPC C07D487/04 C07D498/04 C07D513/04 A61P31/20 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel dihydropyrimidinium compound of formula (I) or a pharmaceutically acceptable salt thereof. In formula (I)

(I)

0–2 of D₁₁–₁₄ separately and independently selected from a single bond, -C(=O)N(R_d3)-, -N(R_d4)-, -S(=O)₂N(R_d6) -, -S(=O)N(R_d7)-, -O-, -S-, -C(=O)O-, -C(=O) - or -S(=O)₂-, and the rest are selected from -C(R_d1)(R_d2)-; L is selected from a single bond, -S-, -NH-, -S(=O)-, -S(=O)₂-, -N(R_d4)-, -[C(R_d1)(R_d2(I)]_0–6; R₂ is selected from

;

D₂₁ is selected from a single bond, -N(R_d4)-, -O-, where Rd₄ is hydrogen; R₂₁ is independently selected from H, C_1–4alkyl, which is optionally substituted with R₀₁, wherein each of R₀₁ is independently selected from F, Cl, Br, I, C_1–10alkyl; R₃ separately and independently selected from following groups, optionally substituted with R₀₁:6–10-membered aromatic ring group or 5–6-member heteroaromatic ring group containing a sulphur atom or a nitrogen atom as a heteroatom, wherein each of R₀₁ is independently selected from F, Cl, Br, I, C₁–₁₀alkyl; R₄ separately and independently selected from following groups, optionally substituted with R₀₁: C₁–₁₀alkyl or 5–6-member heteroaromatic ring group containing nitrogen and sulphur atoms or a nitrogen atom as a heteroatom, wherein each of R₀₁ is independently selected from F, Cl, Br, I, C_1-10alkyl; R_3' is selected from H, C_1-4alkyl; R_d3 and R_d6–₇ separately and independently selected from H, CN, C_1-4alkyl, benzyl optionally substituted with C_1-10alkoxy; R_d4 is selected from H, C_1-4alkyl, CN, or selected from the following groups, optionally substituted with R₀₁: -C(=O)O-C₁–₄alkyl, -S(=O)₂NH-C₁–₄alkyl, -C(=O)-C₁–₄alkyl, -S(=O)₂-C₁–₄alkyl, -C(=O)NH-C₁–₄alkyl, 3–6-member heterocyclylcarbonyl, where heterocyclyl has oxygen as a heteroatom, -C(=O)-C₃–₆cycloalkyl, C₁–₄alkyl-5–6-member heteroaryl with 1–2 heteroatoms selected from nitrogen or oxygen or nitrogen and oxygen, -S(=O)₂-C₃–₆cycloalkyl, -C₁–₄alkyl-C(=O)NH₂, -C₁–₄alkylphenyl, -C₁–₄alkyl-C(=O)O-C₁–₄alkyl, -C₁–₄alkyl-C(=O)OH, 3–6-member heterocyclyl with oxygen as a heteroatom and -C(=S)NH-C₁–₄alkyl, wherein R₀₁ is independently selected from NH₂, C₁–₄alkyl, C₁–₄alkoxy; R_d1–₂ separately and independently selected from H, CN, OH, NH₂, COOH, or selected from the following optionally substituted with R₀₁ groups: C₁–₄alkyl, C₁–₄alkylphenyl, C₀–₄alkyl-3–6-member heterocyclyl with 1–4 heteroatoms selected from nitrogen or oxygen or nitrogen and oxygen, 3–6-member heterocyclylcarbonyl, where heterocyclyl has 1–4 heteroatoms selected from nitrogen or oxygen, or nitrogen and oxygen, or a nitrogen atom and sulfur or sulphoxide thereof, benzenesulphonamido or heterocyclyl sulphonamido, where heterocyclyl has 1–4 heteroatoms selected from nitrogen or oxygen, or nitrogen and oxygen, -D₀₁-D₀₂-D₀₃-H,

;

wherein each of R₀₁ is independently selected from F, Cl, Br, I, CN, OH, NH₂, C₀–₄alkyl-C(=O)OH, C₁–₄alkyl, C₁–₄alkoxy,

,

C₀–₄alkyl-C(=O)O-C₁–₄alkyl; wherein D₀₁ is selected from a single bond, -C₁–₄alkyl-; D₀₂ is selected from O, S, NH, -C(=O)-, -S(=O)₂-, -C(=O)O-, -C(=O)NH-, -C(=S)NH-, -S(=O)₂NH-, -S(=O)NH-, -NHC(=O)O-, -NHC(=O)NH-, -NHC(=NH)NH-, -NHS(=O)₂NH-, -C(=O)NHS(=O)₂-, -NHS(=O)NH-, -C(=O)NHS(=O)-, -C(=N)-, -NH-C(=N)-; D₀₃ is selected from a single bond, -C_1-4alkyl-, -C_2-4alkenyl-, -C_3-6cycloalkyl-, -3–6-membered heterocycloalkyl-, where heterocyclyl has 1–2 heteroatoms selected from nitrogen or oxygen, or nitrogen and oxygen, phenyl, 5–6-member heteroaryl with 1–4 heteroatoms selected from nitrogen or nitrogen and oxygen; optionally R₃ and R_3' are joined together to the same carbon atom to form 9-member bicyclic ring which is optionally substituted with F.

EFFECT: compounds have HBV inhibitor properties and can be used for treating hepatitis B virus.

13 cl, 3 tbl, 226 ex