EP1435926A2 - Methode de traitement et de prevention de troubles du systeme nerveux central associes a une alteration de la neurotransmission glutamatergique par administration de derives de 2-aminobenzenesulfonamide - Google Patents
Methode de traitement et de prevention de troubles du systeme nerveux central associes a une alteration de la neurotransmission glutamatergique par administration de derives de 2-aminobenzenesulfonamideInfo
- Publication number
- EP1435926A2 EP1435926A2 EP02769353A EP02769353A EP1435926A2 EP 1435926 A2 EP1435926 A2 EP 1435926A2 EP 02769353 A EP02769353 A EP 02769353A EP 02769353 A EP02769353 A EP 02769353A EP 1435926 A2 EP1435926 A2 EP 1435926A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- treatment
- prevention
- formula
- compound
- alteration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
Definitions
- AMPAergic synaptic currents due to the activation of the AMPA receptors of cyclothiazide, diazoxide, Hydra21 and 1-BCP is toxic for hippocampal neurons in culture.
- the fact that no side effect of hydra21 has been found in numerous experiments in vivo conducted on experimental animals indicates that the concentrations reached in the brain by this substance in order to exercise its nootropic effect are not sufficient for the excitotoxic effect observed in experiments in cell cultures.
- hydra21 acts as a non-competitive antagonist of the NMDA receptor with neuro- protective properties in vitro, reducing in excitotoxicity experiments the cellular death induced by NMDA.
- hydra21 has a chiral carbon atom, it is possible that only one enantiomer is active, while the other may be inactive or have properties of competitive antagonism with said receptor, so as to compete with the active enantiomer in the same site on the receptor (Uznov et al 1995).
- Uznov et al described how a saline solution of the (+) enantiomer of hydra21 administered per os is more active than a solution with the same concentration of hydra21 in racemic form, in increasing memory and cognitive capacity in experimental animals.
- halogen refers to fluoro, bromo, chloro, iodo atoms
- hydroxy refers to the group -OH.
- thiol refers to the group -SH.
- sulfamoyl refers to the group -SO 2 NH 2 .
- alkyl refers to linear or branched alkyl groups with one to eight carbon atoms.
- substituted alkyl refers to the alkyls described above, made up of one or several functional groups such as aryl, acyl, halogen, hydroxyl, amido, amino, acyloxy, alkoxy, cyano, nitro, thioalkyl and others.
- haloalkyl refers to the groups described above when some or all hydrogens are replaced by halogen atoms (e.g. -CF 3 ).
- aryl refers to aromatic substitutes which may have a single or multiple condensate ring, covalently bound.
- the aromatic rings may contain an ether atom.
- substituted aryl refers to the aryls described above containing one or several functional groups such as acyl, halogen, hydroxyl, amido, amino, acyloxy, alkoxy, cyano, nitro, thioalkyl and others.
- alkoxy refers to the group -OR in which R may be an alkyl, a substituted alkyl, an aryl, a substituted aryl.
- acyl indicates -C(O)R groups in which R is an alkyl or a substituted alkyl or an aryl or an amine group.
- amino indicates an -NRR' group in which R and R' can be independently a hydrogen, alkyl, substituted alkyl, aryl or acyl.
- the purpose of the invention is to supply a method for the treatment or prevention of all disturbances of the central nervous system sensitive to a positive or negative modulation of glutamatergic neurotransmission and, in particular, to a positive or negative modulation of AMPA/Kainate receptors and a negative modulation of NMDA receptors, obtained by administration of a formula I compound.
- the synthesis of the formula I compounds may be carried out by conventional methods known to the specialist in organic synthesis, except for small modifications and already described in the literature (for example patents WO9812185, US6083947, US5488049, WO9942456, etc.). It has been discovered that formula I compounds, as well as their salts with the appropriate acids or bases, have the capacity to positively modulate glutamatergic neurotransmission.
- the compounds under this invention can therefore be used as agents for the activation or inhibition induced by glutamic acid on the AMPA/kainate receptor and NMDA receptor, respectively, and constitute by their activity therapeutic agents for the treatment or prevention of diseases associated with alterations of the glutamatergic system such as: memory, cognitive and sexual disorders due to age, depressive syndromes, anxiety, memory deficit in neuro-degenerative diseases such as Alzheimer's disease, Huntington's chorea and schizophrenia, consequences of acute neuro-degenerative diseases such as ischemia, epilepsy, etc.
- diseases associated with alterations of the glutamatergic system such as: memory, cognitive and sexual disorders due to age, depressive syndromes, anxiety, memory deficit in neuro-degenerative diseases such as Alzheimer's disease, Huntington's chorea and schizophrenia, consequences of acute neuro-degenerative diseases such as ischemia, epilepsy, etc.
- the electrodes were harvested from the borosilicate glass with vertical puller and had a resistance of 5-7 Mohm when refilled with an internal solution of KCl.
- the currents were amplified with an Axopatch ID amplifier, filtered at 5 KHz and digitalized at 10 KHz.
- a pCLAMP software was used for analysis.
- the intracellular solution consisted of (mM): KCl 140, MgCl 2 3, EGTA 5,
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Management, Administration, Business Operations System, And Electronic Commerce (AREA)
Abstract
L'invention porte sur des dérivés de 2-aminobenzènesulfonamide utilisés pour le traitement ou la prévention de troubles du système nerveux central associés à une modulation positive ou négative de la neurotransmission glutamatergique, notamment des troubles de la mémoire et de l'apprentissage, de la schizophrénie, des dysfonctionnements sexuels, d'attaques ischémiques, d'ictus, etc. A titre d'exemple, un composé de formule I est administré afin de traiter ou de prévenir des maladies du système nerveux central présentant une modulation positive ou négative des récepteurs AMPA-Kainate et une modulation négative des récepteurs NMDA.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITBO20010271 | 2001-05-08 | ||
| IT2001BO000271A ITBO20010271A1 (it) | 2001-05-08 | 2001-05-08 | Metodo per il trattamento e la prevenzione dei disturbi del sistema nervoso centrale associati ad una alterazione della neurotrasmissione gl |
| PCT/US2002/014262 WO2002089734A2 (fr) | 2001-05-08 | 2002-05-07 | Methode de traitement et de prevention de troubles du systeme nerveux central associes a une alteration de la neurotransmission glutamatergique par administration de derives de 2-aminobenzenesulfonamide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP1435926A2 true EP1435926A2 (fr) | 2004-07-14 |
| EP1435926A4 EP1435926A4 (fr) | 2005-11-23 |
Family
ID=11439316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP02769353A Withdrawn EP1435926A4 (fr) | 2001-05-08 | 2002-05-07 | Methode de traitement et de prevention de troubles du systeme nerveux central associes a une alteration de la neurotransmission glutamatergique par administration de derives de 2-aminobenzenesulfonamide |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1435926A4 (fr) |
| AU (1) | AU2002308614A1 (fr) |
| IT (1) | ITBO20010271A1 (fr) |
| WO (1) | WO2002089734A2 (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20070182A1 (es) | 2005-07-29 | 2007-03-06 | Wyeth Corp | Derivados cianopirrol-fenil amida como moduladores del receptor de progesterona |
| WO2007076875A2 (fr) * | 2006-01-06 | 2007-07-12 | Aarhus Universitet | Composes agissant sur le transporteur de la serotonine |
| CA2915405A1 (fr) | 2013-06-13 | 2014-12-18 | Veroscience Llc | Compositions et methodes pour le traitement des troubles metaboliques |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0815861A1 (fr) * | 1996-06-28 | 1998-01-07 | F. Hoffmann-La Roche Ag | Sulphonamides et leur utilisation |
| WO2000012073A1 (fr) * | 1998-08-28 | 2000-03-09 | Smithkline Beecham P.L.C. | Utilisation d'antagonistes du 5-ht¿6? |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2722502B1 (fr) * | 1994-07-12 | 1996-08-23 | Adir | Nouveau derive de benzothiadiazine, son procede depreparation et les compositions pharmaceutiques qui le contiennent |
| US6083947A (en) * | 1996-01-29 | 2000-07-04 | The Regents Of The University Of California | Method for treating sexual dysfunctions |
-
2001
- 2001-05-08 IT IT2001BO000271A patent/ITBO20010271A1/it unknown
-
2002
- 2002-05-07 AU AU2002308614A patent/AU2002308614A1/en not_active Abandoned
- 2002-05-07 EP EP02769353A patent/EP1435926A4/fr not_active Withdrawn
- 2002-05-07 WO PCT/US2002/014262 patent/WO2002089734A2/fr not_active Application Discontinuation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0815861A1 (fr) * | 1996-06-28 | 1998-01-07 | F. Hoffmann-La Roche Ag | Sulphonamides et leur utilisation |
| WO2000012073A1 (fr) * | 1998-08-28 | 2000-03-09 | Smithkline Beecham P.L.C. | Utilisation d'antagonistes du 5-ht¿6? |
Non-Patent Citations (2)
| Title |
|---|
| D.J.HEALY ET ALL.: "Iontropic glutamate receptor modulation of 5-HT6 and 5-HT7 mRNA expression in rat brain" NEUROPSYCHOPHARMACOLOGY, vol. 21, no. 3, 1999, pages 341-351, XP002347588 * |
| See also references of WO02089734A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002089734A2 (fr) | 2002-11-14 |
| ITBO20010271A0 (it) | 2001-05-08 |
| ITBO20010271A1 (it) | 2002-11-08 |
| WO2002089734A3 (fr) | 2003-03-06 |
| AU2002308614A1 (en) | 2002-11-18 |
| EP1435926A4 (fr) | 2005-11-23 |
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