NEW P2X7 RECEPTOR ANTAGONISTS, METHOD OF OBTAINING THEM, PHARMACEUTICAL COMPOSITION, METHOD OF TREATMENT AND USE, BASED ON ANTAGONISTS

摘要

FIELD: chemistry.;SUBSTANCE: in this invention, proposal is given of P2X7 receptor antagonists with formula (IA), or its pharmaceutical salt or solvate, where p stands for 0, 1 or 2; each of R¹ independently stands for halogen or C_1-6alkyl, possibly substituted by at least one substitute, chosen from hydroxyl, halogen and C_1-6alkoxy ; q stands for 0, 1 or 2; each of R⁴ independently stands for halogen or C_1-6alkyl, possibly substituted with at least one substitute, chosen from hydroxyl, halogen and C_1-6alkoxy; m stands for 0, 1, 2 or 3; X stands for -C(O)NH- or -NHC(O)-; n stands for 1 or 2; in each CR⁵R⁶ grouping, each of R⁵ and R⁶ independently stands for hydrogen, C_1-6alkyl, or R⁵ and R⁶ together with a carbon atom, to which they are both bonded, can form a 3-6-member cycloalkyl ring; R² is a 4-9-member cycloalkyl ring system, which can be substituted; one of Y or Z is nitrogen, and the other is a CR³ group, where R³ is a group with formula (IIA) where X¹ is an oxygen or sulphur atom, or a N-R¹¹ group, where R¹¹ is hydrogen or a C_1-5alkyl group, which can be substituted; R⁹ is a bond or C_1-5alkyl group, which can be substituted; R¹⁰ is hydrogen, hydroxyl, carboxyl, -C(O)OR²⁰, -NR²¹R²², -C(O)NOH or a -WR²³ group; or R¹⁰ is a 4-9-member carboxylic or heterocyclic ring, each of which can include bridge groups. The carboxylic or heterocyclic ring can be substituted. R²¹ and R²² are independently chosen from hydrogen, C_2-7alkenyl, C_1-6alkylcarbonyl, -SO₂R⁴⁶, -C(O)NHSO₂R⁴⁷, 3-8-member carboxylic or heterocyclic ring, which can be substituted, or R²¹ and R²² can stand for a C_1-7alkyl group, which can be substituted; W and W' independently stand for a bond, O, S(O)_p, -NR⁵⁷C(O)-, -C(O)NR⁵⁸-, -SO₂NR⁵⁹, -NR⁶⁰SO₂-, NR⁶¹, C_1-6 alkylene or a -O(CH₂)_1-6- group, -S(O)_p(CH₂)_1-6-, -NR⁶²(CH₂)_1-6-, -(CH₂)_1-3O(CH₂)_1-3-, -(CH₂)_1-3S(O)_p(CH₂)_1-3-, (CH₂)_1-3NR⁶³(CH₂)_1-3-, -(CH₂)_1-3NR⁶⁴C(O)(CH₂)_0-3-, -(CH₂)_1-3C(O)NR⁶⁵(CH₂)_0-3- or -S(O)_p(CH₂)_1-6NR⁶⁶-; p stands for 0, 1 or 2; R²³ and R²⁴ independently stand for a 3-10-member carboxylic or heterocyclic ring, containing 1-5 heteroatoms, independently chosen from nitrogen, oxygen and sulphur, which can be substituted; each of R⁷, R⁸, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸ and R¹⁹ independently stand for a hydrogen atom or a C_1-6alkyl group, possibly substituted with at least one substitute, chosen from hydroxyl, halogen and C_1-6alkoxy, or any of R⁷ and R⁸, R¹⁴ and R¹⁵, R¹⁶ and R¹⁷ together with a nitrogen atom, to which they are both bonded, can form a 3-8-member saturated heterocyclic ring; each of R²⁰, R³⁴, R³⁷, R⁴⁶, R⁴⁷, R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸, R⁵⁹, R⁶⁰, R⁶¹, R⁶², R⁶³, R⁶⁴, R⁶⁵, R⁶⁶, R⁶⁷ and R⁶⁸ independently stands for hydrogen or C_1-6alkyl group, which can be substituted; each of R²⁵, R²⁶, R²⁷, R²⁸, R³⁰, R³¹, R³², R³³, R³⁵, R³⁶, R³⁸, R³⁹, R⁴⁰, R⁴¹, R⁴², R⁴³, R⁴⁴, R⁴⁵, R⁴⁸, R⁴⁹, R⁵⁰, R⁵¹, R⁵² and R⁵³ independently stands for a hydrogen atom or C_1-6alkyl, C_2-6hydroxyalkyl or C_3-8cycloalkyl group, or any of R²⁵ and R²⁶, R²⁷ and R²⁸, R³⁸ and R³⁹, R⁴¹ and R⁴², R⁴⁸ and R⁴⁹, R⁵⁰ and R⁵¹ together with a nitrogen atom, to which they are both bonded, can form a 3-8-member saturated heterocyclic ring; and R²⁹ is an aryl. Description is also given of the method of obtaining formula IA compounds, pharmaceutical compositions containing these compounds, treatment method based on these compounds and their use in therapy.;EFFECT: obtaining new compounds with useful biological properties.;16 cl, 114 ex