Substituted indenes as medicaments

1. A compound of formula (I):

wherein

R 1 , R 2 and R 3 are independently selected from hydrogen and a branched or unbranched, saturated or unsaturated, C 1-10 aliphatic radical, wherein the aliphatic radical may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a C 3-9 cycloalkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , oxo, —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, with the proviso that R 1 and R 2 are always identical;

R 4 and R 5 together with the bridging nitrogen form a C 3-9 heterocycloalkyl, optionally having at least one additional heteroatom as a ring member and optionally substituted by a branched or unbranched, saturated or unsaturated C 1-10 aliphatic radical or by an aryl group optionally monosubstituted by a C 1-6 alkyl or a halogen; and

R 6 is a (5-6)-membered aryl or (5-6)-membered heteroaryl radical optionally substituted by one or more substituents independently selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1-6 alkoxy group, a phenyl group, wherein the phenyl group may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group;

or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof.

2. The compound according to claim 1 , wherein R 1 , R 2 and R 3 are independently hydrogen or C 1-6 alkyl.

3. The compound according to claim 1 , wherein R 4 and R 5 together with the bridging nitrogen form a group selected from the group consisting of:

wherein each R a is independently selected from hydrogen, a C 1-6 alkyl or a phenyl group optionally substituted by a halogen.

4. The compound according to claim 1 , wherein R 6 is a group selected from the group consisting of:

wherein each R b is independently selected from hydrogen, a C 1-6 alkyl group, —F, —Cl, —I, —Br and a linear or branched C 1-6 alkoxy group.

5. The compound according to claim 1 , wherein R 1 , R 2 and R 3 are independently hydrogen or C 1-6 alkyl;

R 4 and R 5 together with the bridging nitrogen form a group selected from the group consisting of:

wherein each R a is independently selected from hydrogen, a C 1-6 alkyl and a phenyl group optionally substituted by a halogen; and

R 6 is a group selected from the group consisting of:

wherein each R b is independently selected from hydrogen, a C 1-6 alkyl group, —F, —Cl, —I, —Br and a linear or branched C 1-6 alkoxy group.

6. The compound according to claim 1 , which is selected from the group consisting of:

[1] 4-(2-(7-phenyl-1H-inden-3-yl)ethyl)morpholine maleate,

[2] 1-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)azepane hydrochloride,

[3] 4-(2-(7-(pyridin-4-yl)-1H-inden-3-yl)ethyl)morpholine maleate,

[4] 1-(2-(7-(3-fluoropyridin-4-yl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,

[5] 1-methyl-4-(2-(7-phenyl-1H-inden-3-yl)ethyl)piperazine maleate,

[6] 1-phenyl-4-(2-(7-phenyl-1H-inden-3-yl)ethyl)piperazine maleate,

[7] 1-(3-chlorophenyl)-4-(2-(7-phenyl-1H-inden-3-yl)ethy)piperazine maleate,

[8] 1-(2-(7-phenyl-1 H-inden-3-yl)ethy)piperidine maleate,

[9] 1-(2-(7-phenyl-1H-inden-3-yl)ethy)azepane maleate,

[10] 4-phenyl-1-(2-(7-phenyl-1H-inden-3)ethy)piperidine maleate,

[11] 4-(2-(2-methyl-7-phenyl-1H-inden-3-yl)ethyl)morpholine maleate,

[12] 1-methyl-4-(2-(2-methyl-7-phenyl-1H-inden-3-yl)ethyl)piperazine maleate,

[13] 4-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)morpholine maleate,

[14] 1-(2-(7-(4-fluorophenyl)-1H-inden-3-Yl)pethyl)-4-phenylpiperazine maleate,

[15] 1-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)piperidine maleate,

[16] 1-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,

[17] 1-(2-(7-(3-fluorophenyl)-1H-inden-3-yl)pethyl)-4-methylpiperazine maleate,

[18] 4-(2-(7-(3-fluorophenyl)-1H-inden-3-yl)ethyl)morpholine maleate,

[19] 4-(2-(7-(3,4-dichlorophenyl)-1H-inden-3-yl)ethyl)morpholine maleate,

[20] 1-(2-(7-(3,4-dichlorophenyl)-1H-inden-3-yl)pethyl)-4-methylpiperazine maleate,

[21] 4-(2-(7-(4-methoxyphenyl)-1H-inden-3-yl)pethyl)morpholine maleate,

[22] 1-(2-(7-(4-methoxyphenyl)-1H-inden-3-yl)pethyl)-4-methylpiperazine maleate,

[23] 1-(2-(7-(3,4-dimethoxyphenyl)-1H-inden-3-yl)pethyl)-4-methylpiperazine maleate,

[24] 4-(2-(7-(3,4-dimethoxyphenyl)-1H-inden-3-yl)ethyl)morpholine maleate,

[25] 4-(2-(7-(thiophen-3-yl)-1H-inden-3-yl)ethyl)morpholine maleate,

[26] 1-methyl-4-(2-(7-(thiophen-3-yl)-1H-inden-3-yl)ethyl)piperazine maleate,

[27] 1-(2-(7-(1H-1,2,3-triazol-1-yl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,

[28] 3,5-dimethyl-4-(3-(2-(4-methylpiperazin-1-yl)pethyl)-1H-inden-7-yl)isoxazole maleate,

[29] 5-(3-(2-(4-methylpiperazin-1-yl)ethyl)-1H-inden-7-yl)pyrimidine maleate,

[30] 1-methyl-4-(2-(7-(pyridin-4-yl)-1H-inden-3-yl)pethyl)piperazine maleate,

[31] 1-methyl-4-(2-(7-(pyridin-4-yl)-1H-inden-3-yl)ethyl)-1,4-diazepane maleate,

[32] 1-methyl-4-(2-(2-methyl-7-(pyridin-4-yl)-1H-inden-3-yl)ethyl)piperazine maleate,

[33] 1-(2-(7-(2-fluoropyridin-4-yl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,

[34] 4-(2-(7-(pyridin-3-yl)-1H-inden-3-yl)ethyl)morpholine maleate,

[35] 1-methyl-4-(2-(7-(pyridin-3-yl)-1H-inden-3-yl)ethyl)piperazine maleate,

[36] 1-(2-(7-(6-methoxypyridin-3-yl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,

[37] 1-(2-(7-(6-fluoropyridin-3-yl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,

[38] 1-methyl-4-(2-(7-(1-methyl-1H-pyrazol-5-yl)-1H-inden-3-yl)ethyl)piperazine maleate,

[39] 4-(2-(7-(6-methoxypyridin-3-yl)-1H-inden-3-yl)ethyl)morpholine maleate,

[40] 1-methyl-4-(2-(6-pyridin-4-yl)-1H-inden-3-yl)pethyl)piperazine maleate,

[41] 1-(2-(6-(2-fluoropyridin-4-yl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate, and pharmaceutically acceptable salts thereof.

7. A pharmaceutical composition comprising a compound according to claim 1 and at least a pharmaceutically acceptable carrier, additive, adjuvant or vehicle.

8. A process for the preparation of a compound of formula (I):

wherein

R 1 , R 2 and R 3 are independently selected from hydrogen and a branched or unbranched, saturated or unsaturated, C 1-10 aliphatic radical, wherein the aliphatic radical may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a C 3-9 cycloalkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , oxo, —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, with the proviso that R 1 and R 2 are always identical;

R 4 and R 5 together with the bridging nitrogen form a C 3-9 heterocycloalkyl, optionally having at least one additional heteroatom as a ring member and optionally substituted by a branched or unbranched, saturated or unsaturated C 1-10 aliphatic radical or by an aryl group optionally monosubstituted by a C 1-6 alkyl or a halogen; and

R 6 is a (5-6)-membered aryl or (5-6)-membered heteroaryl radical optionally substituted by one or more substituents independently selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1 - 6 alkoxy group, a phenyl group, wherein the phenyl group may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group;

the process comprising reaction between a compound of formula (II):

wherein

R 1 , R 2 and R 3 are independently selected from hydrogen and a branched or unbranched, saturated or unsaturated, C 1-10 aliphatic radical, wherein the aliphatic radical may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a C 3-9 cycloalkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , oxo, —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, with the proviso that R 1 and R 2 are always identical; and

R 6 is a (5-6)-membered aryl or (5-6)-membered heteroaryl radical optionally substituted by one or more substituents independently selected from the group consisting of a C 1 alkyl group, a linear or branched C 1-6 alkoxy group, a phenyl group, wherein the phenyl group may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group;

and a compound of formula (III):

wherein

R 4 and R 5 together with the bridging nitrogen form a C 3-9 heterocycloalkyl, optionally having at least one additional heteroatom as a ring member and optionally substituted by a branched or unbranched, saturated or unsaturated C 1-10 aliphatic radical or by an aryl group optionally monosubstituted by a C 1-6 alkyl or a halogen;

in the presence of a base in an inert solvent, followed by a reduction in the presence of a protic acid and a dehydrating agent, wherein the dehydrating agent is selected from the group consisting of trifluoroacetic acid, aqueous H 2 SO 4 , p-toluenesulfonic acid and aqueous solutions of H 2 SO 4 and acetic acid.

9. A process for the preparation of a compound of formula (I):

wherein

R 1 , R 2 and R 3 are independently selected from hydrogen and a branched or unbranched, saturated or unsaturated, C 1-10 aliphatic radical, wherein the aliphatic radical may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a C 3-9 cycloalkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , oxo, —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, with the proviso that R 1 and R 2 are always identical;

R 4 and R 5 together with the bridging nitrogen form a C 3-9 heterocycloalkyl, optionally having at least one additional heteroatom as a ring member and optionally substituted by a branched or unbranched, saturated or unsaturated C 1-10 aliphatic radical or by an aryl group optionally monosubstituted by a C 1-6 alkyl or a halogen; and

R 6 is a (5-6)-membered aryl or (5-6)-membered heteroaryl radical optionally substituted by one or more substituents independently selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1-6 alkoxy group, a phenyl group, wherein the phenyl group may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group;

the process comprising the reaction between a compound of formula (VI):

wherein X is a halogen;

R 2 and R 3 are independently selected from hydrogen and a branched or unbranched, saturated or unsaturated, C 1-10 aliphatic radical, wherein the aliphatic radical may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a C 3-9 cycloalkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , oxo, —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, with the proviso that R 1 and R 2 are always identical; and

R 4 and R 5 together with the bridging nitrogen form a C 3-9 heterocycloalkyl, optionally having at least one additional heteroatom as a ring member and optionally substituted by a branched or unbranched, saturated or unsaturated C 1-10 aliphatic radical or by an aryl group optionally monosubstituted by a C 1-6 alkyl or a halogen;

and a compound of general formula (V):

wherein each R independently represents a hydrogen or a C 1-6 alkyl or both R groups together with the bridging boron form a boronic cyclic ester; and

R 6 is a (5-6)-membered aryl or (5-6)-membered heteroaryl radical optionally substituted by one or more substituents independently selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1-6 alkoxy group, a phenyl group, wherein the phenyl group may be optionally substituted by one or more substituents selected from the group consisting of a C 1-6 alkyl group, a linear or branched C 1-6 alkoxy group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group, —F, —Cl, —I, —Br, —CF 3 , —CH 2 F, —CHF 2 , —CN, —OH, —SH, —NH 2 , —(C═O)R′, —SR′, —SOR′, —SO 2 R′, —N(C═O) OR′,—NHR′, and —NR′R″ wherein each R′ and R″ independently represents a linear or branched C 1-6 -alkyl group;

in the presence of a base in an inert solvent.