Derivatives of imidazo pyrimido and diazepine pyrimidine-dione, and use thereof as a drug
AssigneeSociete de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)
InventorsLydie Poitout, Valérie Brault
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Abstract
The present invention relates to new derivatives of imidazo, pyrimido and diazepine-pyrimidine-dione of the general formula (I) in which R1, R2, L1, L2, Y, Z and A are various and varying groups. These products exhibit a good affinity for certain sub-types of cannabinoid receptors, in particular the CB2 receptors. They are particularly useful for treating pathological conditions and diseases in which one or more cannabinoid receptors are involved. The invention also relates to pharmaceutical compositions containing said products, and to the use thereof for preparing a drug.
Claims21
Compounds of general formula (I)
- in racemic or enantiomeric form or any combinations of these forms and in which
- L1 represents
- L2 represents
- R1, R2, R3, R4, R5 and R6 represent, independently, a hydrogen atom or a hydroxy, halo, (C1-C8)alkyl, (C1-C8)haloalkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-Cs)cycloalkyl, (C3-C7)heterocycloalkyl, (C1-C6)alkoxy-(C1-C8)alkyl, (C1-C6)alkylthio-(C1-C8)alkyl, aryl, heteroaryl, aralkyloxy, aralkylthio radical or a —(CH2)p—R7 radical, all these radicals being optionally substituted by one or more identical or different substituents chosen from:
- halo, nitro, hydroxy, oxo, amino, carboxamide, (C1-C6)alkylcarbonyl, (C1-C8)alkyl, (C1-C8)haloalkyl, (C1-C8)alkoxy, (C1-C8)haloalkoxy, aryl or aryloxy;
- or R1 and R2, R3 and R4, or R5 and R6, together with the carbon atom to which they are attached, form a (C3-C8)cycloalkyl, (C3-C7)heterocycloalkyl, indanyl, tetrahydronaphthyl or decahydronaphthyl radical, these radicals being optionally substituted by one or more identical or different substituents chosen from:
- halo, hydroxy, (C1-C8)alkyl, (C1-C8)haloalkyl, (C1-C6)alkoxy;
- or finally the R3 and R4 radicals, together with the adjacent R1 and R2 radicals on the one hand or R5 and R6 on the other hand, form a cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl radical, these radicals being optionally substituted by one or more identical or different substituents chosen from halo, nitro, hydroxy, amino, carboxamide, (C1-C6)alkylcarbonyl, (C1-C8)alkyl, (C1-C8)haloalkyl, (C1-C8)alkoxy, (C1-C8)haloalkoxy;
- p represents 1, 2, 3 or 4;
- R7 represents a —C(O)—O—(C1-C8)alkyl, —C(O)—NRNR′N, (C3-C8)cycloalkyl, (C3-C7)heterocycloalkyl, aryl or heteroaryl radical, all these radicals being optionally substituted by one or more identical or different substituents chosen from:
- halo, nitro, hydroxy, amino, (C1-C8)alkyl, (C1-C8)haloalkyl, (C1-C8)alkoxy, (C1-C8)haloalkoxy or aralkyloxy;
- RN and R′N represent independently a hydrogen atom or a (C1-C8)alkyl, (C1-C8)haloalkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C8)cycloalkyl, (C3-C7)heterocycloalkyl, aryl or heteroaryl radical;
- or RN and R′N together form a (C3-C7)heterocycloalkyl radical;
- Z represents a nitrogen atom or a —CH— radical;
- Y represents an oxygen atom, a —CHR8 or —NR8 radical;
- R8 represents a hydrogen atom, a (C1-C6)alkyl or (C1-C6)haloalkyl radical;
- A represents an aromatic or non-aromatic, unsaturated, condensed, mono- or bi-cyclic ring containing optionally one or more identical or different heteroatoms chosen from O, S and N, and optionally substituted by one or more identical or different radicals, chosen from:
- halo, nitro, cyano, oxy, —XA—YA, and aryl optionally substituted by one or more substituents chosen from:
- halo, (C1-C6)alkyl and (C1-C6)haloalkyl;
- XA represents a covalent bond, —O—, —S—, —C(O)—, —NR″N—C(O)—, —C(O)—NR″N—, —C(O)—O—, —SO2— or —SO2NH—;
- YA represents the hydrogen atom or a (C1-C6)alkyl or (C1-C6)haloalkyl radical;
- R″N represents the hydrogen atom or a (C1-C6)alkyl radical;
- n represents 0 or 1;
- m represents 0 or 1;
- or a pharmaceutically acceptable salt thereof.
Compounds according to one of the previous claims, characterized in that A is optionally substituted by one or more identical or different radicals chosen from:
- halo, nitro, —XA—YA, and phenyl;
- XA represents a covalent bond, —O— or —C(O);
- YA represents the hydrogen atom or a (C1-C6)alkyl or (C1-C6)haloalkyl radical;
- or a pharmaceutically acceptable salt thereof.
Compounds according to one of the previous claims, characterized in that A represents a phenyl radical optionally substituted by one or more identical or different (C1-C6)alkyl or (C1-C6)alkoxy radicals;
- or a pharmaceutically acceptable salt thereof.
Compounds according to one of the previous claims, characterized in that Z represents a nitrogen atom;
- or a pharmaceutically acceptable salt thereof.
Compounds according to one of the previous claims, characterized in that Y represents the —NR8 radical and R8 represents a (C1-C6)alkyl radical;
- or a pharmaceutically acceptable salt thereof.
Compounds according to one of the previous claims, characterized in that they correspond to the following formula:
- or a pharmaceutically acceptable salt thereof.
Compounds according to one of the previous claims, characterized in that m represents 0;
- or a pharmaceutically acceptable salt thereof.
Compounds according to one of the previous claims, characterized in that
- n and m represent 0;
- R1 represents the hydrogen atom;
- R2 represents a hydrogen atom or a (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C7)heterocycloalkyl or aryl radical optionally substituted by an aryl, heteroaryl radical, or a —(CH2)p—R7 radical;
- p represents 1 or 2;
- R7 represents a (C3-C8)cycloalkyl or aryl radical;
- or R1 and R2, together with the carbon atom to which they are attached, form a (C3-C8)cycloalkyl or an indanyl radical;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.