Pyrazolecarboxylic acid tricyclic derivatives, preparation and pharmaceutical compositions containing same
View Patent ↗The subject of the invention is tricyclic derivatives of pyrazolecarboxylic acid of formula: in which R 1 represents a C 3 -C 15 carboxyl radical or an NR 2 R 3 group. The invention also relates to the method for preparing the compounds of formula (I), pharmaceutical compositions containing them. The compounds of formula (I) are active on cannabinoid CB 1 receptors.
1. A compound of formula:
in which:
X—Y— represents —(CH 2 ) n —CH 2 —;
n is equal to 1or 2;
g 2 , g 3 , g 4 , g 5 , w 2 , w 3 , w 4 , w 5 , w 6 are identical or different and each independently represent hydrogen, a halogen, a trifluoromethyl, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a (C 1 -C 4 )alkylthio, or a nitro; at least one of the substituents w 2 , w 3 , w 4 , w 5 , w 6 being different from hydrogen;
R 1 represents a nonaromatic C 3 -C 15 carbocyclic radical which is unsubstituted or substituted one or several times with a (C 1 -C 4 )alkyl, or an NR 2 R 3 group;
R 2 and R 3 each separately represent a (C 1 -C 6 )alkyl, or R 2 or R 3 , together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated 5- to 10-membered heterocyclic radical which is unsubstituted or substituted one or several times with a (C 1 -C 4 )alkyl;
or a pharmaceutically acceptable salt or solvate thereof.
2. The compound as claimed in claim 1 , in which g 2 , g 3 , g 5 , w 3 , w 5 , w 6 represent hydrogen and g 4 , w 2 and w 4 have one of the values defined in claim 1 for the compounds of formula (I) except hydrogen.
3. The compound as claimed in claim 2 , in which w 2 and w 4 represent chlorine and g 4 represents chlorine or bromine.
4. The compound as claimed in claim 3 , in which R 1 represents a nonaromatic C 3 -C 15 carbocyclic radical which is unsubstituted or substituted one or several times with a (C 1 -C 4 )alkyl.
5. A compound as claimed in claim 3 , in which R 1 represents NR 2 R 3 , R 2 and R 3 constituting, with the nitrogen atom to which they are attached, a saturated 5- to 10-membered heterocyclic radical which is unsubstituted or substituted one or several times with a (C 1 -C 4 )alkyl.
6. A method for preparing a compound as claimed in claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein a functional derivative of an acid of formula:
in which —X—Y— and g 2 , g 3 , g 4 , g 5 , w 2 , w 3 , w 4 , w 5 , w 6 are defined in claim 1 for the compounds of formula (I), is a compound of formula NH 2 R 1 (III), in which R 1 is as defined for the compounds of formula (I) in claim 1 ,
wherein the functional derivative of the acid is selected from the group consisting of the acid chloride, the anhydride, a mixed anhydride, a C 1 -C 4 alkyl ester in which the alkyl is straight or branched, an ester activated by p-nitrophenyl ester, or the free acid activated with N,N-dicyclohexylcarbodiimide or with benzotriazol-N-oxotris(dimethylamino)-phosphonium hexafluorophosphate.
7. A pharmaceutical composition containing a compound as claimed in claim 1 .
8. The pharmaceutical composition as claimed in claim 7 , in the form of a dosage unit.
9. A pharmaceutical composition containing a compound as claimed in claim 2 .
10. A pharmaceutical composition containing a compound as claimed in claim 3 .
11. A pharmaceutical composition containing a compound as claimed in claim 4 .
12. A pharmaceutical composition containing a compound as claimed in claim 5 .