SUBSTITUTED 6-(1-PIPERAZINYL)-PYRIDAZINES AS 5-HT6 RECEPTOR ANTAGONISTS

• US 20110112107A1
• Filed: 07/01/2009
• Published: 05/12/2011
• Est. Priority Date: 07/03/2008
• Status: Active Grant

• Current Assignee: JANSSEN-CILAG S.A., EDIFICIO JOHNSON & JOHNSON, JANSSEN-CILAG S.A., EDIFICIO JOHNSON& JOHNSON
• Original Assignee: Janssen-Cilag BV (Johnson & Johnson)
• Inventors: Bartolomé-Nebreda, José Manuel, Conde-Ceide, Susana, Delgado-Jiménez, Francisca, Van Gool, Michiel Luc Maria, MacDonald, Gregor James
• Granted Patent: US 8,530,474 B2
• Time in Patent Office: Days
• US Class Current: 514/252.02
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07D 237/20 Nitrogen atoms nitro radicals C07D237/12
• CPC Class Codes: C07D 237/22 : Nitrogen and oxygen atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present invention is concerned with novel substituted 6-(1-piperazinyl)-pyridazines of Formula (I)

wherein R¹, R², R³ and X have the meaning defined in the claims, having 5-HT₆-antagonistic properties. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said novel compound as an active ingredient as well as the use of said compounds as a medicine.

Claims

1. A compound of formula (I)

2. The compound according to claim 1 wherein

R¹ is trifluoromethyl;

R² is phenyl or phenyl substituted with fluoro;

R³ is hydrogen, methyl or pyridinylmethyl;

X is —

O—

, —

NH—

, —

CH₂—

, —

CH(OH)—

, —

SO₂—

, —

CO—

, —

NH—

CH₂—

, —

O—

CH₂—

,

1,2-ethenediyl or ethynediyl;

or a pharmaceutically acceptable addition salt or a solvate thereof.

3. The compound according to claim 1 wherein

R² is phenyl or phenyl substituted with one fluoro.

4. The compound according to claim 1 wherein the compound is N-(4-fluorophenyl)-6-(1-piperazinyl)-3-(trifluoromethyl)-4-pyridazinamine

5. The compound according to claim 1 wherein the compound is N-(4-fluorophenyl)-6-(1-piperazinyl)-3-(trifluoromethyl)-4-pyridazinamine .2.5 HCl 0.5 H₂O.

7. A method of treatment or prevention of conditions wherein cognition is impaired comprising administering a therapeutically effective amount of the compound of claim 1 to a patient in need of treatment wherein the conditions wherein congition is impaired are selected from the group consistin of;

Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Schizophrenia, Huntingdon'"'"'s disease, Lewy Body Dementia, dementia due to HIV disease, dementia due to Creutzfeldt-Jakob disease;

amnestic disorders;

mild cognitive impairment; and

age-related cognitive decline;

for the treatment and/or prevention of feeding disorders and diseases, for the regulation of appetite;

for the maintenance, increase or reduction of body weight;

anorexia, bulimia, obesity, cachexia, type II diabetes (non insulin dependent diabetes mellitus), type II diabetes caused by obesity;

for the treatment and/or prevention of stroke;

migraine;

head trauma;

epilepsy;

irritable colon syndrome;

irritable bowl syndrome;

for the treatment of disorders of the central nervous system;

schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified;

psychosis associated with dementia;

major depressive disorder, dysthymic disorder, premenstrual dysphoric disorder, depressive disorder not otherwise specified, Bipolar I disorder, bipolar II disorder, cyclothymic disorder, bipolar disorder not otherwise specified, mood disorder due to a general medical condition, substance-induced mood disorder, mood disorder not otherwise specified;

generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, acute stress disorder, post-traumatic stress disorder;

mental retardation;

pervasive developmental disorders;

attention deficit disorders, attention-deficit/hyperactivity disorder, disruptive behaviour disorders;

personality disorder of the paranoid type, personality disorder of the schizoid type, personality disorder of the schizotypical type;

tic disorders, Tourette'"'"'s syndrome;

trichotillomania;

convulsive disorder;

seizure;

substance dependence;

substance abuse;

substance withdrawal;

drug addiction and/or withdrawal;

nicotine addiction and/or withdrawal; and

alcohol addiction and/or withdrawal.

8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as defined in claim 1.

9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as defined in claim 2.

10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as defined in claim 3.

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as defined in claim 4.

12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as defined claim 5.

6. (canceled)