FIELD: chemistry.
SUBSTANCE: invention relates to new quinazolinone derivatives of formula I in form of a free base or acid addition salt, with agonist properties towards cannabinoid (CB) receptor. The compounds can be used for treating or preventing diseases or conditions, where cannabinoid receptor plays a role or is activated, particularly eye diseases, for example glaucoma. In compounds of formula I
R1, R2, R3, R4 and R5 are independently hydrogen; halogen; C1-C4alkyl, which is optionally substituted with C1-C4alkoxycarbonyl; C3-C7cycloalkyl; C3-C7cycloalkylC1-C4alkyl; C1-C4alkylcarboxy; SO2R10; cyano; -SO2N(R10)R11; -S-R10 or -SOR10; or R1 and R2 or R2 and R3, together with carbon atoms to which they are bonded, form an aromatic or aliphatic carbocyclic group with 5 to 10 ring atoms, or an aromatic or aliphatic heterocyclic group, with 5 to 10 ring atoms, from which one, two or three heteroatoms are selected from nitrogen, oxygen and sulphur; R6 is -CH2-O-C(O)-N(R12)R13, -CH2-X-C(O)-R14, C1-C4alkyl or hydroxyC1-C4alkyl; R7, R8 and R9 are independently C1-C4alkyl; R10 and R11 are independently hydrogen, C1-C4alkyl; C2-C4alkenyl; C3-C7cycloalkyl; C3-C7cycloalkylC1-C4alkyl; C1-C4alkoxyC1-C4alkyl; C1-C4alkylcarboxy; hydroxyC1-C4alkoxyC1-C4alkyl; hydroxy; hydroxyC1-C4alkyl; phenylC1-C4alkyl which are optionally substituted with hydroxy, C1-C4alkoxy, carboxy, C1-C4alkoxycarbonylC1-C4alkyl, C1-C4alkoxycarbonyl, cyano; or R10 and R11 together form an aliphatic heterocyclic group, with 5 to 10 ring atoms, from which one, two or three heteroatoms are selected from nitrogen, oxygen and sulphur; R12 and R13 are independently hydrogen, C1-C4alkyl, C2-C4alkenyl, C3-C7cycloalkyl, C3-C7cycloalkylC1-C4alkyl, C1-C4alkoxyC1-C4alkyl, hydroxyC1-C4alkoxyC1-C4alkyl, hydroxyC1-C4alkyl, dihydroxyC1-C4alkyl, C1-C4alkoxycarbonylC1-C4alkyl, C1-C4alkoxycarbonyl, cyano, -SO2R10, -SO2N(R10)R11, -S-R10, -SOR10, -C1-C4-alkylene-NH-SO2R10, C1-C4-alkylene-SOR10, -C1-C4-alkylene-NH-SO2R10, -C1-C4-alkylene-CON(R10)R11, -CON(R10)R11, -C1-C4-alkylene-C(O)OR10, fluoroalkyl, or R12 and R13 form a substituted or unsubstituted aliphatic heterocyclic group, with 5 to 10 ring atoms, where the substitutes are selected from a group which consists of hydroxymethyl, hydroxy or oxo group; R14 is NH, C1-C4alkyl-NH-, C2-C4alkenyl-NH-, C3-C7cyclalkyl-NH-, C3-C7cycloalkylC1-C4alkyl-NH-, C1-C4alkoxyC1-C4alkyl-NH-, hydroxyC1-C4alkoxyC1-C4alkyl-NH-, hydroxyC1-C4alkyl-NH-, dihydroxyC1-C4alkyl-NH-, C1-C4alkoxycarbonylC1-C4alkyl-NH-, C1-C4alkoxycarbonyl-NH-, -NH-C1-C4-alkylene-CN, -NH-SO2R10, -NH-SO2N(R10)R11, -NH-C1-C4-alkylene-S-R10, -NH-SOR10, -NH-C1-C4-alkylene-SO2R10, -NH-C1-C4-alkylene-SOR10, -NH-C1-C4-alkylene-NH-SO2R10, -NH-C1-C4-alkylene-CON(R10)R11, -NH-CON(R10)R11, -NH-C1-C4-alkylene-C(O)OR10, -NH-fluoroalkyl or unsubstituted aliphatic heterocyclic group, with 5 to 10 ring atoms; X is O or CH2.
EFFECT: obtaining new quinazolinone derivatives of formula I in form of a free base or acid addition salt, with agonist properties towards cannabinoid (CB) receptor.
16 cl, 112 ex
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