CONDENSED DERIVATIVES OF AZOLPYRIMINE WITH INHIBITING PROPERTIES OF PHOSPHATIDYL INOSITOL-3-KINASE (PI3K) Russian patent published in 2008 - IPC C07D487/04 C07D487/06 A61K31/519 A61P29/00 

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to new condensed derivatives of azolpyrimidine of formula (I), their tautomeric or stereoisomeric form and their physiologically accepted salts. Compounds of this invention have improved activity of phosphatidyl inositol-3-kinase (P13K) inhibiting, specifically of P13K-γ inhibiting, and can be applied for production of medicinal agents for prevention and treatment of P13K- and P13K-γ activity based diseases. Those diseases are inflammatory and immunoregulatory diseases such as asthma and others. In compounds of formula (I) . X means CR⁵R⁶ or NH; Y¹ means CR³ or N; chemical bond between means single bond or double bond, as long as means double bond, then Y² and Y³ mean CH, and as long as mean single bond, then Y² and Y³ mean regardless CR³R⁴; Z¹, Z², Z³ and Z⁴ mean redardless CH , CR² or N; R¹ means phenyl, optionally containing 1 to 3 substitutes selected from group including R¹¹, C_3-8cycloalkyl, optionally containing 1 to 3 substitutes selected from group including R¹¹, C_1-6alkyl, optionally containing as substitutes one or more halogen atoms, or 3-15-component mono- or bicyclic heterocyclic ring being saturated or non-saturated, optionally containing 1 to 3 substitutes selected from group including R¹¹, and containing 1 to 3 heteroatoms selected from group including N, O and S, where R¹¹ means halogen, nitro-, hydroxyl-, cyano-, carboxy-, amino-, N-(C_1-6alkyl)amino-, K-(hydroxyC_1-6alkyl)amino-, N,N-di(C_1-6alkyl)amino-, N(C_1-6acyl)amino-, N-(formyl)-N-(C_1-6 alkyl) amino-, N-(C_1-6alkansulphonyl)amino-, N-(carboxy C_1-6 alkyl)-N-(C_1-6 alkyl) amino-, N-(C_1-6 alkansulphonyl)amino-, N-[N,N-di(C₁.₆ alkyl)aminomethylene] amino-, N-[N,N-di(C_1-6 alkyl)amino(C_1-6 alkyl)methylene]amino-, N-[N,N-di(C_1-6 alkyl)aminoC_1-6alkenyl]amides, aminocarbonyl, N-(C_1-6 alkyl)aminocarbonyl, N,N-di(C_1-6 alkyl)aminocarbonyl, C_3-8 cycloalkyl, C_1-6alkylthio, C_1-6 alkansulphonyl, sulphamoyl, C_1-6alkoxycarbonyl, phenylC_1-6alkoxycarbonyl, where specified phenylic fragment optionally contains 1 to 3 substitutes selected from group including R¹⁰¹, C_1-6alkyl, optionally containing as substitutes 1, 2 or 3 halogen atoms, C_1-6alkoxy, optionally containing as substitutes 1, 2 or 3 halogen atoms, or 5- 7-component saturated or non-saturated ring containing 1 to 3 heteroatoms selected from group containing N, and optionally containing 1 to 3 substitutes selected from group including and R¹⁰¹, where R¹⁰¹ means halogen, carboxy, amino-, N-(C_1-6alkyl)amino-, N,N-di(C_1-6alkyl)amino-, aminocarbonyl, N-(C_1-6alkyl)aminocarbonyl, N,N-di(C_1-6alkyl)aminocarbonyl, C_1-6alkyl, and C_1-6alkoxy; R² mean hydroxy, halogen, nitro-, cyano-, amino-, N-(C_1-6alkyl)amino-, N,N-di(C_1-6alkyl)amino-, N-(hydroxyC_1-6alkyl)amino-, N-(hydroxyC_1-6alkyl)-N-(C_1-6alkyl)amino-, C_1-6 acoxy, aminoC_1-6 acoxy, C_2-6alkenyl, phenyl, 5-7-compound saturated or non-saturated heterocyclic ring containing 1 to 2 heteroatoms selected from group including O and N, and optionally containing as substitutes: hydrohy, d-balkyl, N-(C_1-6acyl)amino-, phenyl, phenylC_1-6alkyl, C_1-6alkyl, optionally containing as substitutes R²¹, or C_1-6alkoxy, optionally containing as substitutes R²¹, where R²¹ means cyano group, 1, 2 or3 halogen atoms, hydroxy, amino-, N-(C_1-6alkyl)amino-, N,N-di(C_1-6alkyl)amino-, C_1-6alkoxy, hydroxyC_1-6alkoxy, -C(O)-R²⁰¹, -NHC(O)-R²⁰¹, C_3-8 cycloalkyl, phthalymidil, 2-oxo-1,3-oxazolidinyl, phenyl or 5- or 6-compound saturated or non-saturated heterocyclic ring containing 1 to 4 heteroatoms selected from group including O and N, and optionally containing as substitutes hydroxy, C_1-6alkyl, N-(C_1-6acyl)amides or benzyl, where R²⁰¹ means hydroxyl, amino-, N-(C_1-6alkyl)amino-, N,N-di(C_1-6alkyl)amino-, N-(halogenphenylC_1-6 alkyl)amides, C_1-6alkyl, aminoC_1-6alkyl, C_1-6alkoxy, 5- or 6-compound saturated or non-saturated heterocyclic ring containing 1 to 2 heteroatoms selected from group including O and N; R³ means hydrogen, halogen, aminocarbonyl or C_1-6alkyl, optionally containing as substitutes phenylC_1-6alkoxy or 1, 2 or 3 halogen atoms; R⁴ means hydrogen or C_1-6alkyl; R⁵ means hydrogen or C_1-6alkyl; and R means halogen, hydrogen or C_1-6alkyl. Invention also refers to medicinal agent, inhibition method and compound application.

EFFECT: compounds under this invention have improved activity.

16 cl, 2 tbl, 18 ex