Patent EA-003831-B1 (EA)
Title: New cyano-indole serotonin-reuptake inhibitor compound, method of preparing and containing their pharmaceutical composition
Inventor: LAVIELLE GILBERT
IPC: C07D487/04
Filed: 2000-10-11
Abstract: 1. A compound selected from those of formula (I): wherein: R1 and R2 each independently represent hydrogen, or linear or branched (C1-C6)alkyl, T1 and T2 each independently represent linear or branched (C1-C6)alkylene, G represents a heterocyclic group selected from those of formula (alpha) or (beta) wherein: W1 to W5 and X1 to X4 are defined as follows: W1, W2 and W3 each independently represent nitrogen, CR5, NR4, or CO, W4 represents nitrogen, CR3, NR4 or CO, W5 represents carbon or nitrogen, X1 represents a bond, nitrogen or CR3, or NR4, X2 to X4 each independently represent CR3, NR4, CO, SR4, SO2 oxygen, sulphur, or nitrogen, R3 represents hydrogen, halogen, linear or branched (C1-C6)alkyl, hydroxy, linear or branched (C1-C6)perhaloalkyl, nitro, or amino optionally substituted by one or two groups selected from linear or branched (C1-C6)alkyl, benzyl, R4 represents hydrogen, linear or branched (C1-C6)alkyl, optionally substituted aryl, or optionally substituted arylalkyl, R5 represents R3, or two adjacent groups R5 form, together with the carbon atoms carrying them, a saturated, partially unsaturated or unsaturated mono- or bi-cyclic group optionally containing 1 to 5 hetero atoms selected from nitrogen, oxygen and sulphur, said group being optionally substituted by one or more groups selected from R3 or oxo, it being understood that, in formulae (alpha) and (beta), at least one heteroatom is present, the dotted lines indicate that the groups in question may contain an unsaturated bond or a plurality of conjugated or unconjugated unsaturated bonds and that, if there is no unsaturated bond, the remaining valences are occupied by hydrogen atoms, the groups (alpha) and (beta) being linked to T2 by any one of their ring junctions, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically-acceptable acid or base. 2. A compound of formula 1 of claim 1, wherein the cyano group is attached in the 5-position of the indole ring system, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically-acceptable acid or base. 3. A compound of formula 1 of claim 1, wherein the cyano group is attached in the 6-position of the indole ring system, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically-acceptable acid or base. 4. A compound of formula 1 of claim 1, wherein R1 and R2 each represents hydrogen, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically acceptable acid or base. 5. A compound of formula 1 of formula (I) according to claim 1, wherein T1 represents methylene, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically acceptable acid or base. 6. A compound of formula 1 of claim 1, wherein G is selected from the group consisting of: 2-furyl; 2,4-dioxo-1,4-dihydro-3(2H)-quinazolinyl; 3-oxo-[1,2,4]triazolo[4,3-a]-pyridin-2(3H)-yl; 1-oxo-2(1H)-phthalazinyl; 7-methyl-5-oxo-5H-[1,3]thiazolo-[3,2-a]pyrimidin-6-yl; 6-chloro-2-oxo-2,3-dihydro-1H-indol-5-yl; 2-oxo-2,3-dihydro-1H-indol-5-yl; 2-oxo-1,2,3,4-tetrahydro-6-quinolinyl; 3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-1(2H)-pyrimidinyl; 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl; 1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl; 1,3-dioxo-3,6-dihydropyrrolo-3,4-c]carbazol-2(1H)-yl; 1,3-dioxo-1,3-dihydro-2H-benzo[c]isoindol-2-yl; and 3,5-dimethyl-2,6-dioxo-3,6-dihydro-1(2H)-pyrimidinyl, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically acceptable acid or base. 7. A compound of formula 1 of claim 1, wherein R1 and R2 each represents hydrogen, T1 represents methylene, T2 represents alkylene and G is selected from the group consisting of 2-furyl; 2,4-dioxo-1,4-dihydro-3(2H)-quinazolinyl; 3oxo-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl; 1-oxo-2(1H)-phthalazinyl; 7-methyl-5-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidin-6-yl; 6chloro-2-oxo-2,3-dihydro-1H-indol-5-yl; 2-oxo-2,3-dihydro-1H-indol-5-yl; 2-oxo-1,2,3,4-tetrahydro-6-quinolinyl; 3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-1(2H)-pyrimidinyl; 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl; 1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl; 1,3-dioxo-3,6-dihydropyrrolo[3,4-c]carbazol-2(1H)-yl; 1,3-dioxo-1,3-dihydro-2H-benzo[c]isoindol-2-yl; and 3,5-dimethyl-2,6-dioxo-3,6-dihydro-1(2H)-pyrimidinyl, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically acceptable acid or base. 8. A compound of formula 1 of claim 7, wherein the cyano group is attached in the 5-position of the indole ring system, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically acceptable acid or base. 9. A compound of formula 1 of claim 7, wherein the cyano group is attached in the 6-position of the indole ring system, its enantiomers, diastereoisomers, or addition salts thereof with a pharmaceutically acceptable acid or base. 10. A compound of formula 1 of claim 1 which is 3-({1-[2-(7-methyl-5-oxo-5H)-[1,3]thiazolo[3,2-a]pyrimidin-6-yl)ethyl]-3-pyrrolidinyl}methyl)-1H-indole-5-carbonitrile hydrochloride. 11. A compound of formula 1 of claim 1 which is 3-({1-[2-(6-chloro-2-oxo-2,3-dihydro-1H-indol-5-yl)ethyl]-3-pyrrolidinyl}-methyl)-1H-indole-5-carbonitrile hydrochloride. 12. A pharmaceutical compositions comprising as active ingredient at least one compound of claims 1 to 11 and in combination with one or more inert, non-toxic pharmaceutically acceptable excipients or vehicles. 13. A pharmaceutical compositions of claim 12 comprising as active ingredient at least one compound of claims 1 to 11 intended for production of medicaments used as serotonin-reuptake inhibitor while treating depressions, obsessive-compulsive disorders, phobias, impulsive disorders, related to wrong consumption of drugs, bulimia nervosa and anxiety.