1,2,3-triazole-4-amine derivatives for the treatment of sigma receptor related diseases and disorders
The present invention relates to new 1,2,3-triazole-amine derivatives, having affinity for sigma receptors, especially sigma-1 receptor, as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments for the treatment of sigma receptor related diseases and disorders.
1. A 1,2,3-triazole-4-amine derivative of general formula (I):
wherein:
G 1 is selected from the group consisting of a hydrogen atom; a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a —(C═O)—R 5 group; a —(SO) 2 —R 6 group; and a —C═Z—NH—R 8 group;
R 1 and R 2 , which may be identical or different, are selected from the group consisting of a hydrogen atom; and a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical;
or
R 1 and R 2 together with the bridging nitrogen atom to which they are attached form an at least mono-cyclic, substituted or unsubstituted, at least one heteroatom containing heterocyclyl group which is optionally condensed with a substituted or unsubstituted mono- or polycyclic ring system;
R 4 is selected from the group consisting of a hydrogen atom; a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted cycloalkyl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a branched or unbranched, saturated or unsaturated, substituted or unsubstituted alkyl-cycloalkyl group in which the cycloalkyl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system; and a branched or unbranched, saturated, substituted or unsubstituted alkyl-aryl group in which the aryl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system;
R 5 is selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted cycloalkyl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a substituted or unsubstituted heterocyclyl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a branched or unbranched, saturated or unsaturated, substituted or unsubstituted alkyl-cycloalkyl group in which the cycloalkyl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, substituted or unsubstituted alkyl-aryl group in which the aryl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system; and a branched or unbranched, saturated, substituted or unsubstituted alkyl-heterocyclyl group in which the heterocyclyl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system;
R 6 is selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; and a branched or unbranched, saturated or unsaturated, substituted or unsubstituted alkyl-cycloalkyl group in which the cycloalkyl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system;
Z is S or O;
R 8 is a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical;
n is 1, 2, 3, or 4;
optionally as a stereoisomer, including enantiomers and diastereomers, a racemate or as of a mixture of at least two stereoisomers, including enantiomers and/or diastereomers, in any mixing ratio, or a salt thereof, or a solvate thereof.
2. The 1,2,3-triazole-4-amine derivative according to claim 1 , wherein
G 1 is selected from the group consisting of a hydrogen atom; a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical; an substituted or unsubstituted, at least six membered aryl group; a —(C═O)—R 5 group; a —(SO) 2 —R 6 group; and a —C═Z—NH—R 8 group.
3. The 1,2,3-triazole-4-amine derivative according to claim 2 , wherein
R 5 is selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical; an substituted or unsubstituted, C 3 -C 6 cycloalkyl group; and an substituted or unsubstituted, at least six-membered aryl group;
R 6 is selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical; and an substituted or unsubstituted, at least six-membered aryl group;
Z is S or O; and
R 8 is a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical.
4. The 1,2,3-triazole-4-amine derivative according to claim 3 , wherein
G 1 is selected from the group consisting of a hydrogen atom; a substituted or unsubstituted ethyl group; a substituted or unsubstituted propyl group; a substituted or unsubstituted benzyl group; a
—(C═O)—R 5 group; a —(SO) 2 —R 6 group; and a —C═Z—NH—R 8 group; and
R 5 is selected from the group consisting of a substituted or unsubstituted methyl group; a substituted or unsubstituted tert-butyl group; a substituted or unsubstituted cyclopropane group; a substituted or unsubstituted cyclohexyl group; and a substituted or unsubstituted phenyl group, wherein the substituents are selected from halogen;
R 6 is selected from the group consisting of a substituted or unsubstituted methyl group; and a substituted or unsubstituted phenyl group, wherein the substituents are selected from halogen;
Z is S or O; and
R 8 is a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical.
5. The 1,2,3-triazole-4-amine derivative according to claim 1 wherein
R 1 and R 2 , which may be identical or different, are selected from the group consisting of a hydrogen atom; and a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical;
or
R 1 and R 2 together with the bridging nitrogen atom to which they are attached form a mono-cyclic, substituted or unsubstituted, at least one heteroatom containing C 5 -C 7 heterocyclyl group, which is optionally condensed with an substituted or unsubstituted mono- or polycyclic ring system; wherein the heteroatom is selected from the group consisting of N, S, O; the heterocyclyl group and/or mono- or polycyclic ring system being unsubstituted or substituted, wherein the substituents are selected from the group consisting of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, and C 3 -C 6 cycloalkyl.
6. The 1,2,3-triazole-4-amine derivative according to claim 5 , wherein
R 1 and R 2 , which may be identical or different, are selected from the group consisting of a hydrogen atom; and a linear or branched, substituted or unsubstituted ethyl group;
or
R 1 and R 2 together with the bridging nitrogen atom to which they are attached form a substituted or unsubstituted heterocyclyl group, selected from the group consisting of a pyrrolidine group, a piperazine group, a piperidine group, a morpholine group, an azepane group or an oxazepane group; the heterocyclyl group being unsubstituted or substituted, wherein the substituents are selected from the group consisting of a methyl group, an ethanone group, a fluoro group, a chloro group and a cyclohexyl group.
7. The 1,2,3-triazole-4-amine derivative according to claim 1 , wherein
R 4 is selected from the group consisting of an substituted or unsubstituted C 6 -C 10 cycloalkyl group, which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a substituted or unsubstituted at least six membered aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a branched or unbranched, saturated or unsaturated, substituted or unsubstituted alkyl-cycloalkyl group in which the cycloalkyl group is at least six membered and may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system; and a branched or unbranched, saturated, substituted or unsubstituted alkyl-aryl group in which the aryl group is at least six membered and/or condensed with a mono- or polycyclic ring system; the heterocyclyl group and/or mono- or polycyclic ring system being unsubstituted or substituted; wherein the substituents are selected from halogen.
8. The 1,2,3-triazole-4-amine derivative according to claim 7 , wherein
R 4 is selected from the group consisting of a substituted or unsubstituted cyclohexyl group; a substituted or unsubstituted adamantyl group; a substituted or unsubstituted phenyl group; a substituted or unsubstituted benzyl group; and a substituted or unsubstituted naphtalene group, wherein the substituents are selected from fluoro and chloro.
9. The 1,2,3-triazole-4-amine derivative according to claim 1 , wherein
n is 1 or 2.
10. The 1,2,3-triazole-4-amine derivative according to claim 1 , wherein
G 1 is selected from the group consisting of a hydrogen atom; a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical; a substituted or unsubstituted, at least six membered aryl group; a —(C═O)—R 5 group; a —(SO) 2 —Re group; and a —C═Z—NH—R 8 group;
R 1 and R 2 , which may be identical or different, are selected from the group consisting of a hydrogen atom; and a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical;
or
R 1 and R 2 together with the bridging nitrogen atom to which they are attached form a mono-cyclic, substituted or unsubstituted, at least one heteroatom containing C 5 -C 7 heterocyclyl group, which is optionally condensed with a substituted or unsubstituted mono- or polycyclic ring system; wherein the heteroatom is selected from the group consisting of N, S, O; the heterocyclyl group and/or mono- or polycyclic ring system being unsubstituted or substituted, wherein the substituents are selected from the group consisting of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, and C 3 -C 6 cycloalkyl;
R 4 is selected from the group consisting of an substituted or unsubstituted C 6 -C 10 cycloalkyl group, which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a substituted or unsubstituted, at least six membered aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a branched or unbranched, saturated or unsaturated, substituted or unsubstituted alkyl-cycloalkyl group in which the cycloalkyl group is at least six membered and may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system; and a branched or unbranched, saturated, substituted or unsubstituted alkyl-aryl group in which the aryl group is at least six membered and/or condensed with a mono- or polycyclic ring system; the heterocyclyl group and/or mono- or polycyclic ring system being unsubstituted or substituted, wherein the substituents are selected from halogen;
R 5 is selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical; a substituted or unsubstituted, C 3 -C 6 cycloalkyl group; and an substituted or unsubstituted, at least six-membered aryl group;
R 6 is selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical; and a substituted or unsubstituted, at least six-membered aryl group;
Z is S or O; and
R 8 is a linear or branched, saturated or unsaturated, substituted or unsubstituted C 1-4 alkyl radical.
11. The 1,2,3-triazole-4-amine derivative according to claim 1 , wherein
G 1 is selected from the group consisting of a hydrogen atom; an ethyl group; a propyl group; a substituted or unsubstituted benzyl group; a —(C═O)—R 5 group; a —(SO) 2 —R 6 group; and a —C═Z—NH—R 8 group, wherein the substituents are chloro;
R 1 and R 2 , each represent an ethyl group;
or
R 1 and R 2 together with the bridging nitrogen atom to which they are attached form a heterocyclyl group selected from the group consisting of a pyrrolidine group, a piperazine group, a piperidine group, a morpholine group, an azepane group, and an oxazepane group; the heterocyclyl group being unsubstituted or substituted, wherein the substituents are selected from the group consisting of a methyl group, an ethanone group, a fluoro, a chloro and a cyclohexyl group;
R 4 is selected from the group consisting of a cyclohexyl group; an adamantyl group; a substituted or unsubstituted phenyl group, a substituted or unsubstituted benzyl group, and a naphtalene group; wherein the substituents are selected from fluoro and chloro;
R 5 is selected from the group consisting of a methyl group; a tert-butyl group; a cyclopropane group; a cyclohexyl group; and a phenyl group;
R 6 is selected from the group consisting of a methyl group; and a substituted phenyl group, wherein the substituent is chloro;
Z is S;
R 8 is propyl; and
n is 1 or 2.
12. The 1,2,3-triazole-4-amine derivative according to claim 1 , which is selected from the group consisting of:
1-(4-(2-(1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-ylamino)ethyl)piperazin-1-yl)ethanone hydrochloride;
1-(3,4-dichlorophenyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(2,4-dichlorophenyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-benzyl-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-dichlorophenyl)-N-(2-morpholinoethyl)-i H-1,2,3-triazol-4-amine hydrochloride;
1-(1-adamantyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-dichlorobenzyl)-N-(2-morpholinoethyl)-H-1,2,3-triazol-4-amine hydrochloride;
1-benzyl-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-dichlorobenzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-dichlorobenzyl)-N-(3-(piperidin-1-yl)propyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3-fluorophenyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(azepan-1-yl)ethyl)-1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(azepan-1-yl)ethyl)-1-(3-fluorophenyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(azepan-1-yl)ethyl)-1-(1-adamantyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(azepan-1-yl)ethyl)-1-benzyl-1H-1,2,3-triazol-4-amine hydrochloride;
1-benzyl-N-(2-(4-methylpiperazin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(4-fluorobenzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3-fluorobenzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-benzyl-N-(2-(pyrrolidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3-fluorophenyl)-N-(2-(pyrrolidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N1-(1-benzyl-1H-1,2,3-triazol-4-yl)-N2,N2-diethylethane-1,2-diamine hydrochloride;
N-(2-morpholinoethyl)-1-(naphthalen-1-yl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-dichlorophenyl)-N-(3-morpholinopropyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-cyclohexyl-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(4-fluorobenzyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-dichlorobenzyl)-N-(3-morpholinopropyl)-1H-1,2,3-triazol-4-amine;
1-(4-fluorobenzyl)-N-(3-morpholinopropyl)-1H-1,2,3-triazol-4-amine;
1-cyclohexyl-N-(3-morpholinopropyl)-1H-1,2,3-triazol-4-amine;
1-cyclohexyl-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-cyclohexyl-N-(2-(4-cyclohexylpiperazin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(4-cyclohexylpiperazin-1-yl)ethyl)-1-(3-fluorophenyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(1,4-oxazepan-4-yl)ethyl)-1-(3-fluorophenyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(1,4-oxazepan-4-yl)ethyl)-1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(4-cyclohexylpiperazin-1-yl)ethyl)-1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-amine;
1-(4-chlorophenyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-difluorobenzyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-difluorobenzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(2,4-difluorophenyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(4-chlorophenyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-difluorobenzyl)-N-(2-(4,4-difluoropiperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-(4,4-difluoropiperidin-1-yl)ethyl)-1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-difluorophenyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-difluorophenyl)-N-(2-(4,4-difluoropiperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(4-fluorophenyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3-chloro-4-fluorophenyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3-fluorophenyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-difluorophenyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(4-fluorophenyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
N-(2-((2RS*,6SR*)-2,6-dimethylpiperidin-1-yl)ethyl)-1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-amine;
1-(2,4-difluorophenyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine;
1-(4-(2-(1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-ylamino)ethyl)piperazin-1-yl)ethanone hydrochloride;
N-(1-(1-adamantyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl)cyclopropanecarboxamide hydrochloride;
N-(1-(1-adamantyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl)cyclohexanecarboxamide hydrochloride;
N-(1-(1-adamantyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl)benzamide hydrochloride;
N-(1-(1-adamantyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl)pivalamide hydrochloride;
N-(1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl)acetamide hydrochloride;
N-(1-(1-adamantyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl)acetamide hydrochloride;
N-(1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl)acetamide hydrochloride;
N-(1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl)methane sulfonamide hydrochloride;
4-chloro-N-(1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)-N-(2-morpholinoethyl) benzenesulfonamide hydrochloride;
1-(3,4-dichlorophenyl)-N-(2-morpholinoethyl)-N-propyl-1H-1,2,3-triazol-4-amine hydrochloride;
1-benzyl-N-(2-chlorobenzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-amine;
1-(3,4-dichlorobenzyl)-N-(3-(piperidin-1-yl)propyl)-N-propyl-1H-1,2,3-triazol-4-amine;
1-(1-adamantyl)-N-ethyl-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(3,4-dichlorophenyl)-N-ethyl-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride;
1-(1-adamantyl)-N-(2-morpholinoethyl)-N-propyl-1H-1,2,3-triazol-4-amine hydrochloride;
N-(4-chlorobenzyl)-1-(1-adamantyl)-N-(2-morpholinoethyl)-1H-1,2,3-triazol-4-amine hydrochloride; and
1-(1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)-1-(2-morpholinoethyl)-3-propylthiourea hydrochloride
or a pharmaceutically acceptable salt, prodrug or solvate thereof.
13. A process for the production of a 1,2,3-triazole-4-amine derivative of general formula (I):
wherein
G 1 is selected from the group consisting of a hydrogen atom; a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a —(C═O)—R 5 group; a —(SO) 2 —R 6 group; and a —C=Z—NH—R 8 group;
R 1 and R 2 , which may be identical or different, are selected from the group consisting of a hydrogen atom; and a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical;
or
R 1 and R 2 together with the bridging nitrogen atom to which they are attached form an at least mono-cyclic, substituted or unsubstituted, at least one heteroatom containing heterocyclyl group which is optionally condensed with a substituted or unsubstituted mono- or polycyclic ring system; and
R 4 is selected from the group consisting of a hydrogen atom; a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted cycloalkyl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; and a branched or unbranched, saturated or unsaturated, substituted or unsubstituted alkyl-cycloalkyl group in which the cycloalkyl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, substituted or unsubstituted alkyl-aryl group in which the aryl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system;
R 5 is selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted cycloalkyl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a substituted or unsubstituted heterocyclyl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; a branched or unbranched, saturated or unsaturated, substituted or unsubstituted alkyl-cycloalkyl group in which the cycloalkyl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, substituted or unsubstituted alkyl-aryl group in which the aryl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system; and a branched or unbranched, saturated, substituted or unsubstituted alkyl-heterocyclyl group in which the heterocyclyl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system;
R 6 is selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems; and a branched or unbranched, saturated or unsaturated, substituted or unsubstituted alkyl-cycloalkyl group in which the cycloalkyl group may be substituted or unsubstituted and/or condensed with a mono- or polycyclic ring system;
Z is S or O;
R 8 is a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; and
n is 1, 2, 3, or 4,
wherein a compound of formula (III):
wherein PG 1 represents a nitrogen-protecting group,
is reacted with a compound of formula (VI):
wherein X represents chloro, bromo or iodo and PG 2 represents a nitrogen-protecting group, under copper catalyzed alkynylation conditions, to yield a compound of formula (VII):
which compound of formula (VII) is subjected to deprotection conditions to selectively remove the PG 2 protecting group, wherein the deprotection reaction is optionally carried out in an aprotic solvent, including THF, with an appropriate reagent, including TBAF, followed by a cycloaddition reaction with an organic azide of formula (VIII):
wherein the cycloaddition reaction is optionally carried out in situ by the addition of catalytic amounts of a Cu(l) salt, and an excess of a base, including a tertiary amine including DIPEA, to yield a compound of formula (IX):
which compound of formula (IX) is subjected to N-deprotection conditions to yield a compound of formula (Ia):
(i.e., the compound of formula (I) wherein G 1 represents a hydrogen atom), which compound of formula (Ia) may be further reacted with an acylating agent of formula (X):
to yield a compound of formula (I) wherein G 1 represents a —(C═O)—R 5 group;
or
the compound of formula (Ia) may be further reacted with a compound of formula (XI):
to yield a compound of formula (I), wherein G 1 represents an —(SO) 2 —R 6 group;
or
the compound of formula (Ia) may be further reacted with an aldehyde under reductive amination conditions to yield a compound of formula (I), wherein G 1 represents a linear or branched, saturated or unsaturated, substituted or unsubstituted aliphatic radical; a substituted or unsubstituted aryl group which is optionally condensed to other, substituted or unsubstituted, mono- or polycyclic ring systems;
or
the compound of formula (Ia) may be further reacted with a compound of formula (XIII):
R 8 NCZ, (XIII)
to yield a compound of formula (I), wherein G 1 represents a —C═Z—NH—R 8 group.
14. A pharmaceutical composition comprising one or more 1,2,3-triazole-4-amine derivatives of general formula (I) according to claim 1 , or solvates or prodrugs thereof, and at least one pharmaceutically acceptable excipient.