WO2003080050A1 - The use of 3-[1-[2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]-6-chloro-1h-indole or its enantiomers for the treatment of diseases and disorders responsive to 5-ht (serotonin) re-uptake inhibition - Google Patents
The use of 3-[1-[2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]-6-chloro-1h-indole or its enantiomers for the treatment of diseases and disorders responsive to 5-ht (serotonin) re-uptake inhibition Download PDFInfo
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- the present invention relates to the use of 3-[l-[2-(l-acetyl ⁇ 2,3 ⁇ dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole, its enantiomers and pharmaceutically acceptable salts thereof for the preparation of medicaments useful for the treatment of diseases or disorders responsive to 5- ⁇ T (serotonin) re-uptake inhibition.
- 5-HT re-uptake inhibitors are useful for the treatment of depression, anxiety disorders and other affective disorders, including generalised anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
- 5-HT re-uptake inhibitors are effective in the treatment of dysthymic disorder (Thase et al. Arch Gen Psychiatry 1996, 53, 777-784).
- 5-HT re-uptake inhibitors are also useful in the treatment of anxiety disorders. Clinical studies have shown that 5-HT re-uptake inhibitors have beneficial effects in generalized anxiety disorder (see e.g. Rocca et al. Ada Psychiatr Scand 1997, 95, 444-450). It is also well accepted that 5-HT re-uptake inhibitors are effective against panic anxiety/panic disorder (see e.g. Sheehan and Harnett-Sheehan J Clin Psychiatry 1996, 10, 51-58).
- 5-HT re-uptake inhibitors appear also effective in the treatment of impulse control disorders (Durst et al. CNS Drugs 2001, 15, 185-195; Hollander et al. Psychiatr Clin North Am 2000, 23, 629-642; Christenson and Crow J Clin Psychiatry 1996, Suppl 8, 42-47).
- 5-HT re-uptake inhibition may reduce aggression, probably due to positive effects on the serotonergic dysfunction that is implicated in aggressive behaviour directed towards oneself or others (for review see Walsh & Dinan Acta Psychiatr Scand 2001, 104, 84-91).
- 5-HT re-uptake inhibitors are effective in the treatment of premenstrual syndrom (see e.g. Eriksson et al. Neuropsychopharmacology 1995, 12, 167-176).
- 5-HT re-uptake inhibitors may also be useful in treatment of alcohol abuse (see Sellers et al. J Clin Psychiatry 1991, 52, 49-54). Therefor, 5-HT re- uptake inhibitors may be beneficial in the treatment of drug abuse.
- 5-HT re-uptake inhibitors have been demonstrated to be effective in the treatment of both bulimia nervosa as well as in anorexia nervosa (see Kaye et al. Biol Psychiatry 1998, 44, 825-838). Clinical studies have indicated that treatment with 5-HT re-uptake inhibitors show superiority over placebo in reducing the frequency of binge eating episodes (Goldstein et al. Br J Psychiatry 1995, 166, 660-666). Moreover, published data suggest that 5-HT re-uptake inhibitors improves outcome and prevents relapse in people with anorexia nervosa (Kaye et al. Biol Psychiatry 1998, 44, 825-838). Thus, it seems clear that 5-HT re-uptake inhibitors are useful in the pharmacotherapy of eating disorders including bulimia and anorexia.
- WO 98/28293 describes a series of substituted indane or dihydroindole compounds having effect at dopamine D 4 receptors. The compounds described are considered useful for the treatment of a range of psychiatric and neurological disorders, including the positive and negative symptoms of schizophrenia and other psychoses.
- potent dopamine D 4 ligand may be particularly useful for the treatment of disorders responsive to inhibition of 5- ⁇ T re-uptake.
- the present invention relates to the use of 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole having the formula (I), any of its enantiomers or pharmaceutically acceptable salts thereof for the treatment of diseases or disorders responsive to inhibition of 5- ⁇ T re-uptake.
- the invention relates to the use of (S)-(+)-3-[l-[2-(l-acetyl-2,3-dihydro-lH- indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole or pharmaceutically acceptable salts thereof for the treatment of diseases or disorders responsive to inhibition of 5- ⁇ T re-uptake.
- the present invention also relates to the use of 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole having formula (I), or any of its enantiomers, but in particular (S)-(+)-3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole, or pharmaceutically acceptable salts thereof for the preparation of a pharmaceutical composition for the treatment of diseases or disorders responsive to inhibition of 5- ⁇ T re-uptake.
- Diseases and disorders responsive to inhibition of 5-HT re-uptake are depression, anxiety disorders and other affective disorders, including generalised anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
- generalised anxiety disorder panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder
- eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
- the disease to be treated according with the invention is depression.
- the compound 3-[l-[2-(l-acetyl-2,3-dihydro- lH-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole and its enantio- mers are very potent 5- ⁇ T re-uptake inhibitors.
- the 5-HT re-uptake inhibiting effect of this compound and its enantiomers is equipotent with the well-known antidepressant drugs citalopram and fluoxetine.
- the present invention covers the use of both the racemate of the compound of formula (I) and each of its enantiomers for the treatment of diseases or disorders responsive to 5- HT re-uptake inhibition.
- the compound of formula (I) and its enantiomers and pharmaceutically acceptable salts thereof may be prepared as described in WO 98/28293, see in particular examples 20 and 34.
- the pharmaceutical formulations of the invention may be prepared by conventional methods in the art.
- tablets may be prepared by mixing the active ingredient with ordinary adjuvants and/or diluents and subsequently compressing the mixture in a conventional tabletting machine.
- adjuvants or diluents comprise: corn starch, potato starch, talcum, magnesium stearate, gelatine, lactose, gums, and the like. Any other adjuvants or additives usually used for such purposes such as colourings, flavourings, preservatives etc. may be used provided that they are compatible with the active ingredients.
- Solutions for injections may be prepared by dissolving the active ingredient and possible additives in a part of the solvent for injection, preferably sterile water, adjusting the solution to desired volume, sterilising the solution and filling it in suitable ampules or vials. Any suitable additive conventionally used in the art may be added, such as tonicity agents, preservatives, antioxidants, etc.
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Abstract
The use of 3-[1-[2-(1-acetyl-2,3-dihydro-1H-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-1H-indole, any of its enantiomers or pharmaceutically acceptable salts thereof for the preparation of a pharmaceutical composition for the treatment of diseases and disorders responsive to 5-HT re-uptake inhibition.
Description
The use of 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3-yl)ethyl]-3,6-dihydro-2H- pyridin-4-yl]-6-chloro-lH-indole or its enantiomers for the treatment of diseases and disorders responsive to 5-HT (serotonin) re-uptake inhibition.
The present invention relates to the use of 3-[l-[2-(l-acetyl~2,3~dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole, its enantiomers and pharmaceutically acceptable salts thereof for the preparation of medicaments useful for the treatment of diseases or disorders responsive to 5-ΗT (serotonin) re-uptake inhibition.
Background of the Invention
5-HT re-uptake inhibitors are useful for the treatment of depression, anxiety disorders and other affective disorders, including generalised anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
Thus, there are mounting evidence showing that blockade of 5-HT re-uptake has antidepressant effects in patients (Montgomery Psychopharmacology: The fourth generation of progress, ed: Meltzer HY, Raven Press, New York, 1995, pp 1043-1051).
- Today, treatment with 5-HT re-uptake inhibitors is the standard first-line treatment for major depression (Berman et al. Neurobiology of mental illness, eds: Clwney DS, Nestler EJ, Bunney BS, Oxford University Press, Oxford, 1999, 31, 419-432). Furthermore, it is well recognised that 5-HT re-uptake inhibitors are effective in the treatment of dysthymic disorder (Thase et al. Arch Gen Psychiatry 1996, 53, 777-784).
5-HT re-uptake inhibitors are also useful in the treatment of anxiety disorders. Clinical studies have shown that 5-HT re-uptake inhibitors have beneficial effects in generalized anxiety disorder (see e.g. Rocca et al. Ada Psychiatr Scand 1997, 95, 444-450). It is also well accepted that 5-HT re-uptake inhibitors are effective against panic anxiety/panic disorder (see e.g. Sheehan and Harnett-Sheehan J Clin Psychiatry 1996,
10, 51-58). Clear efficacy of 5-HT uptake inhibitors has also been demonstrated in obsessive compulsive disorder (McDougle Neurobiology of mental illness, eds: Charney DS, Nestler EJ, Bunney BS, Oxford University Press, Oxford, 1999, 37, 518-533). There is accumulating data implicating the central 5-HT system in the pathogenesis of post traumatic stress disorder (Charney et al. Arch Gen Psychiatry 1993, 50, 295-305). In line with this, 5-HT re-uptake inhibitors have been shown efficacious in post traumatic stress disorder .and these type of agents are generally the first line of treatment of this disorder (Rothbaum et al. J Trauma Stress 1996, 9, 865-871; Goddard et al. Neurobiology of mental illness, eds: Charney DS, Nestler EJ, Bunney BS, Oxford University Press, Oxford, 1999, 39, 548-563). Furthermore, clinical data indicate that blockade of the 5-HT re-uptake has beneficial effects in the treatment of acute stress disorder (Robert et al. J Burn Care Rehabil 1999, 20, 250-258.) 5-HT re-uptake inhibitors are also useful in the treatment of phobia, particularly social phobia anxiety disorder. Thus, clinical studies have indicated a role of the central 5-HT system in the patophysiology of phobias (Potts et al. hit Clin Psychopharmacol 1996, 11, Suppl 3, 43- 48) and it is well accepted that 5-HT re-uptake inhibitors are effective in treating social phobia/anxiety disorder (see e.g. van den Linden et al. Int Clin Psychopharmacol 2000, 15, Suppl 2, 15-23).
5-HT re-uptake inhibitors appear also effective in the treatment of impulse control disorders (Durst et al. CNS Drugs 2001, 15, 185-195; Hollander et al. Psychiatr Clin North Am 2000, 23, 629-642; Christenson and Crow J Clin Psychiatry 1996, Suppl 8, 42-47). In particular, 5-HT re-uptake inhibition may reduce aggression, probably due to positive effects on the serotonergic dysfunction that is implicated in aggressive behaviour directed towards oneself or others (for review see Walsh & Dinan Acta Psychiatr Scand 2001, 104, 84-91).
Both clinical and preclinical studies indicate that the central 5-HT system is involved in cognitive functions. For example, drug-induced destruction of 5-HT terminals, as evident by a reduction in 5-HT re-uptake sites, is associated with impaired memory in both animals and humans (Morgan Psychopharmacology 1999, 141, 30-36). It has also been shown that blockade of the 5-HT re-uptake improves cognitive function in elderly depressed patients (Meltzer et al. Neuropsychopharmacology 1998, 18, 407-430). Finally, treatment with agents that increase serotonergic neurotransmission has been
reported to ameliorate cognitive deficits in schizophrenic patients (Sumiyoshi et al. Am J Psychiatry 2001, 158, 1722-1725). These findings collectively suggest that 5-HT re- uptake inhibitors may be effective in the treatment of cognitive disorders.
It has previously been described that 5-HT re-uptake inhibitors are effective in the treatment of premenstrual syndrom (see e.g. Eriksson et al. Neuropsychopharmacology 1995, 12, 167-176).
Several findings support that serotonergic mechanisms are involved in the discriminative, reinforcing and subjective effects of drugs of abuse (see e.g. Walsh and Cunningham Psychopharmacology 1997, 130, 41-58). Thus, studies in hum,ans have shown that blockade of the 5-HT re-uptake attenuates the subjective effects of psychomotor stimulants such as cocaine (Walsh et al. J Clin Psychopharmacology,
1994, 14, 396-407). 5-HT re-uptake inhibitors may also be useful in treatment of alcohol abuse (see Sellers et al. J Clin Psychiatry 1991, 52, 49-54). Therefor, 5-HT re- uptake inhibitors may be beneficial in the treatment of drug abuse.
5-HT re-uptake inhibitors have been demonstrated to be effective in the treatment of both bulimia nervosa as well as in anorexia nervosa (see Kaye et al. Biol Psychiatry 1998, 44, 825-838). Clinical studies have indicated that treatment with 5-HT re-uptake inhibitors show superiority over placebo in reducing the frequency of binge eating episodes (Goldstein et al. Br J Psychiatry 1995, 166, 660-666). Moreover, published data suggest that 5-HT re-uptake inhibitors improves outcome and prevents relapse in people with anorexia nervosa (Kaye et al. Biol Psychiatry 1998, 44, 825-838). Thus, it seems clear that 5-HT re-uptake inhibitors are useful in the pharmacotherapy of eating disorders including bulimia and anorexia.
Finally, clinical studies have indicated a beneficial role of 5-HT re-uptake inhibitors in pharmacological intervention of obesity. Thus, treatment with 5-HT re-uptake inhibitors has been reported to be effective in inducing significant weight loss in both obese males and females (Ricca et al. J Endocrinol Invest 1996, 19, 727-733; Lawton et al. Obes Res
1995, 3, 345-356).
WO 98/28293 describes a series of substituted indane or dihydroindole compounds having effect at dopamine D4 receptors. The compounds described are considered useful for the treatment of a range of psychiatric and neurological disorders, including the positive and negative symptoms of schizophrenia and other psychoses.
It has now, surprisingly, been found that a compound of WO 98/28293, namely 3-[l-[2- (l-acetyl-2,3-dihydro-lH-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH- indole having the formula
which is described herein as a potent dopamine D4 ligand, may be particularly useful for the treatment of disorders responsive to inhibition of 5-ΗT re-uptake.
Summary of the Invention
Thus, the present invention relates to the use of 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole having the formula (I), any of its enantiomers or pharmaceutically acceptable salts thereof for the treatment of diseases or disorders responsive to inhibition of 5-ΗT re-uptake.
In particular, the invention relates to the use of (S)-(+)-3-[l-[2-(l-acetyl-2,3-dihydro-lH- indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole or pharmaceutically acceptable salts thereof for the treatment of diseases or disorders responsive to inhibition of 5-ΗT re-uptake.
The present invention also relates to the use of 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole having formula (I), or any of its enantiomers, but in particular (S)-(+)-3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole, or pharmaceutically acceptable salts thereof for the preparation of a pharmaceutical composition for the treatment of diseases or disorders responsive to inhibition of 5-ΗT re-uptake.
Diseases and disorders responsive to inhibition of 5-HT re-uptake are depression, anxiety disorders and other affective disorders, including generalised anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
Preferably, the disease to be treated according with the invention is depression.
Detailed Description of the Invention
The compound 3 -[ 1 -[2-(l -acetyl-2,3-dihydro- lH-indol-3 -yl)ethyl]-3 ,6-dihydro- 2H-pyridin-4-yl]-6-chloro-lH-indole and its enantiomers were first disclosed in WO 98/28293. This application also contains data showing that the compounds are potent dopamine D4 ligands. Although it is indicated that some of the compounds disclosed in WO 98/28293 have effect at 5-ΗTιA and 5-HT2 receptors and/or have 5-HT re-uptake inhibiting effect, the application is silent as regards the effect of 3-[l-[2-(l-acetyl-2,3- dihydiO-lH-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole and its enantiomers at these receptors and the 5-ΗT transporter.
It has now surprisingly been found that the compound 3-[l-[2-(l-acetyl-2,3-dihydro- lH-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole and its enantio- mers are very potent 5-ΗT re-uptake inhibitors. The 5-HT re-uptake inhibiting effect of this compound and its enantiomers is equipotent with the well-known antidepressant drugs citalopram and fluoxetine.
The present invention covers the use of both the racemate of the compound of formula (I) and each of its enantiomers for the treatment of diseases or disorders responsive to 5- HT re-uptake inhibition.
The compound of formula (I) and its enantiomers and pharmaceutically acceptable salts thereof may be prepared as described in WO 98/28293, see in particular examples 20 and 34.
Pharmacological Testing
3-[l-[2-(l-Acetyl-2,3-dihydro-lH-indol-3-yl)ethyl]-3,6-dihydiO-2H-pyridin-4-yl]-6- chloro-lH-indole and its enantiomers were tested in a well-recognised and reliable test for measuring 5-ΗT re-uptake inhibition.
Using this method, the ability of the drugs to inhibit the accumulation of [3H]-5-HT into whole rat brain synaptosomes is determined in vitro. The assay was performed as described by Hyttel, J. Psychopharmacology 1978, 60, 13.
Both the racemic mixture and each of the enantiomers of 3-[l-[2-(l-acetyl-2,3-dihydro- lH-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole have an IC5n value below 9 nM in this test.
Formulation
The pharmaceutical formulations of the invention may be prepared by conventional methods in the art.
Thus, tablets may be prepared by mixing the active ingredient with ordinary adjuvants and/or diluents and subsequently compressing the mixture in a conventional tabletting machine. Examples of adjuvants or diluents comprise: corn starch, potato starch, talcum, magnesium stearate, gelatine, lactose, gums, and the like. Any other adjuvants or additives usually used for such purposes such as colourings, flavourings,
preservatives etc. may be used provided that they are compatible with the active ingredients.
Solutions for injections may be prepared by dissolving the active ingredient and possible additives in a part of the solvent for injection, preferably sterile water, adjusting the solution to desired volume, sterilising the solution and filling it in suitable ampules or vials. Any suitable additive conventionally used in the art may be added, such as tonicity agents, preservatives, antioxidants, etc.
Claims
1. The use of 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3-yl)ethyl]-3,6- dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole having the formula
or any of its enantiomers or pharmaceutically acceptable salts thereof for the preparation of a pharmaceutical composition for the treatment of diseases and disorders responsive to 5-ΗT re-uptake inhibition.
2. The use according to claim 1 wherein the compound used is (S)-(+)-3-[l-[2-(l- acetyl-2,3-dihydro-lH-indol-3-yl)ethyl]-3,6-dihydiO-2H-pyridin-4-yl]-6-chloro-lH-indole or a pharmaceutically acceptable salt thereof.
3. The use according to claim 1 wherein the compound used is (R)-(-)-3-[l-[2-(l- acetyl-2,3-dihydro-lH-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole or a pharmaceutically acceptable salt thereof.
4. The use according to claims 1-3 wherein the disease or disorder responsive to 5-
ΗT re-uptake inhibition is selected from depression, anxiety disorders and other affective disorders, including generalised anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
5. The use according to claim 4 wherein the disease or disorder responsive to 5-HT re-uptake inhibition is depression.
6. A method for the treatment of diseases or disorders responsive to 5-HT re- uptake inhibition comprising administering 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol- 3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloiO-lH-indole having the formula
or any of its enantiomers or pharmaceutucally acceptable salts thereof to an individual in need thereof.
7. The method according to claim 6 wherein the compound used is (S)-(+)-3-[l-[2-(l- acetyl-2,3-dihydro- lH-indol-3-yl)ethyl]-3 ,6-dihydro-2H-pyridin-4-yl]-6-chloro- lH-indole or a pharmaceutically acceptable salt thereof.
8. The method according to claim 6 wherein the compound used is (R)-(-)-3-[l-[2-(l- acetyl-2,3-dihydro-lH-indol-3-yl)ethyl]-3,6-dihydro-2H-ρyridin-4-yl]-6-chloro-lH-indole or a pharmaceutically acceptable salt thereof.
9. The method according to claims 6-8 wherein the disease or disorder responsive to 5-ΗT re-uptake inhibition is selected from depression, anxiety disorders and other affective disorders, including generalised anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
10. The method according to claim 9 wherein the disease or disorder responsive to 5- HT re-uptake inhibition is depression.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003215529A AU2003215529A1 (en) | 2002-03-27 | 2003-03-26 | The use of 3-(1-(2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl)-3,6-dihydro-2h-pyridin-4-yl)-6-chloro-1h-indole or its enantiomers for the treatment of diseases and disorders responsive to 5-ht (serotonin) re-uptake inhibition |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36843602P | 2002-03-27 | 2002-03-27 | |
| DKPA200200479 | 2002-03-27 | ||
| US60/368,436 | 2002-03-27 | ||
| DKPA200200479 | 2002-03-27 |
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| WO2003080050A1 true WO2003080050A1 (en) | 2003-10-02 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998028293A1 (en) * | 1996-12-20 | 1998-07-02 | H.Lundbeck A/S | Indane or dihydroindole derivatives |
-
2003
- 2003-03-26 AU AU2003215529A patent/AU2003215529A1/en not_active Abandoned
- 2003-03-26 WO PCT/DK2003/000210 patent/WO2003080050A1/en not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998028293A1 (en) * | 1996-12-20 | 1998-07-02 | H.Lundbeck A/S | Indane or dihydroindole derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003215529A1 (en) | 2003-10-08 |
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