| 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 C1-6alkyl, possibly substituted by at least one substitute, chosen from hydroxyl, halogen and C1-6alkoxy ; q stands for 0, 1 or 2; each of R4 independently stands for halogen or C1-6alkyl, possibly substituted with at least one substitute, chosen from hydroxyl, halogen and C1-6alkoxy; 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, C1-6alkyl, 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 C1-5alkyl group, which can be substituted; R9 is a bond or C1-5alkyl 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, C2-7alkenyl, C1-6alkylcarbonyl, -SO2R46, -C(O)NHSO2R47, 3-8-member carboxylic or heterocyclic ring, which can be substituted, or R21 and R22 can stand for a C1-7alkyl 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, C1-6 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 C1-6alkyl group, possibly substituted with at least one substitute, chosen from hydroxyl, halogen and C1-6alkoxy, 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 C1-6alkyl 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 C1-6alkyl, C2-6hydroxyalkyl or C3-8cycloalkyl 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 |
