NOVEL PHOSPHATE COMPOUNDS, SYNTHESIS METHOD THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME Russian patent published in 2017 - IPC A61K31/675 C07F9/09 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I), its enantiomers and pharmaceutically acceptable salts and compositions based thereon, which can be used in oncology:

where X and Y represent C or N, but cannot be identical, A₁ and A₂ together with atoms bearing them form heterocycle Het, selected from 5,6,7,8-tetrahydroindolizine or indolizine, or A₁ and A₂ represent H, (C₁-C₆)polyhaloalkyl or (C₁-C₆)alkyl, T represents H, (C₁-C₆)alkyl, optionally substituted with one-three halogen atoms, (C₁-C₄)alkyl-NR₁R₂, or (C₁-C₄)alkyl-OR₆, R₁ and R₂ represent H or (C₁-C₆)alkyl, or R₁ and R₂ with a nitrogen atom bearing them form heterocycloalkyl, R₃ represents a cycloalkyl, heterocycloalkyl, aryl or heteroaryl, R₄ is phenyl, substituted in para-position with a group -OPO(OM)(OM'), -OPO(OM)(O^-M₁⁺), -OPO(O^-M₁⁺)(O^-M₂⁺), -OPO(O^-)(O^-)M₃²⁺, -OPO(OM)(O[CH₂CH₂O]_nCH₃), or -OPO(O^-M₁⁺)(O[CH₂CH₂O]_nCH₃), where M and M ' denote H, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, cycloalkyl or heterocycloalkyl from 5 or 6 members, while M₁⁺ , M₂⁺ and M₃²⁺ represent pharmaceutically acceptable cations, n ranges from 1 to 5, wherein carbon atoms of previous groups or their possible substitutes can be deuterated, R₅ represents H or halogen, (C₁-C₆)alkyl or (C₁-C₆)alkoxy, R₆ represents H or (C₁-C₆)alkyl, R_a, R_b, R_c and R_d represents R₇, halogen, (C₁-C₆)alkoxy, hydroxy, NR₇R₇'-CO-(C₀-C₆)alkyl-O-, or substitutes of pair (R_b, R_c) together with carbon atoms, bearing them, form a ring of 5–7 members with 1 or 2 heteroatoms, selected from O and S, wherein one or more carbon atoms of ring can be deuterated or substituted with 1–3 groups, selected from halogen and (C₁-C₆)alkyl, R₇ and R₇' are H, (C₁-C₆)alkyl, or R₇ and R₇' together with a nitrogen atom, bearing them, form heterocycle, consisting of 5–7 members, "aryl" denotes phenyl, naphthyl, biphenyl or indenyl, "heteroaryl" denotes a mono- or bicyclic group, consisting of 5–10 members with at least one aromatic fragment and 1–4 heteroatoms, selected from O, S and N, "cycloalkyl" denotes a mono- or bicyclic, non-aromatic, carboxylic group consisting of 3–10 members, "heterocycloalkyl" denotes a mono-or bicyclic, non-aromatic, condensed or grouped from 3–10 ring members with 1–3 heteroatoms, selected from O, S, SO, SO₂ and N, aryl, heteroaryl, cycloalkyl and heterocycloalkyl groups, alkyl, alkenyl, alkynyl and alkoxy can be substituted with 1–3 groups, selected from (C₁-C₆)alkyl, (C₃-C₆)spiro, (C₁-C₆)alkoxy, (C₁-C₆)alkyl-S-, hydroxyl, oxo or N-oxide, nitro, cyano, -COOR', -OCOR', NR'Rʺ, (C₁-C₆)polyhaloalkyl, trifluoromethoxy, (C₁-C₆)alkylsulphonyl, halogen, aryl, heteroaryl, aryloxy, arylthio, cycloalkyl, heterocycloalkyl, optionally substituted with one or more halogens or alkyls, R' and Rʺ are H or (C₁-C₆)alkyl, Het group can be substituted with 1–3 groups, selected from (C₁-C₆)alkyl, hydroxy, (C₁-C₆)alkoxy, NR₁'R₁ʺ and halogen, wherein R₁' and R₁ʺ assume values, defined for groups R' and Rʺ.

EFFECT: disclosed are novel effective anticancer agents and an efficient method for preparing them.

33 cl, 25 ex, 11 tbl