Pyrazole compounds

• US 20060276650A1
• Filed: 03/08/2004
• Published: 12/07/2006
• Est. Priority Date: 04/05/2003
• Status: Active Grant

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Inventors: Schiemann, Kai, Seyfried, Christoph, Schadt, Oliver, Bartoszyk, Gerd, Van Amsterdam, Christoph
• Granted Patent: US 7,960,413 B2
• Time in Patent Office: Days
• US Class Current: 544/364
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• 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 25/20 Hypnotics; Sedatives
• 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 25/36 Opioid-abuse
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 403/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings

Abstract

Compounds of the formula (I) and salts and solvates thereof, in which X, R¹, R², R³, R⁴, R⁵ and R⁶ have the meanings indicated in Claim 1, are suitable as ligands of 5 HT receptors.

Claims

1. Compounds of the formula I

2. Compounds of the formula I according to claim 1, in which R⁶ denotes phenyl, 2-, 3- or 4-cyanophenyl, 2-, 3- or 4-fluorophenyl, 2-, 3- or 4-methyl-, ethyl-, n-propyl- or n-butylphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5- or 3,6-difluoro-, dichloro- or dicyanophenyl, 3,4,5-trifluorophenyl, 3,4,5-trimethoxy- or triethoxyphenyl, thiophen-2-yl or thiophen-3-yl.

3. Compounds of the formula I according to claim 1, in which R⁴ denotes H, Hal, CN, A or NO₂.

4. Compounds of the formula I according to claim 1, in which R² denotes H or alkyl.

5. Compounds of the formula I according to claim 1, in which R³ denotes phenyl, 2-, 3- or 4-cyanophenyl, 2-, 3 or 4-fluorophenyl, 2-, 3- or 4-methyl-, ethyl-, n-propyl- or n-butylphenyl, 2,3-, 2,4-, 2,5-, 2,6-difluoro- or dicyanophenyl, thiophen-2-yl or thiophen-3-yl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, quinolinyl, isoquinolinyl, 2- or 4-pyridazyl, 2-, 4- or 5-pyrimidyl, 2- or 3-pyrazinyl or 2- or 3-furanyl.

6. Compounds of the formula I according to claim 1, in which X has the meaning N.

7. Compounds of the formulae IA, IB, IC, ID, IE and IF:

8. Process for the preparation of compounds of the formula IA

9. Process for the preparation of compounds of the formula IB

10. Compounds of the formula I according to claim 1 and physiologically acceptable salts and solvates thereof as medicaments.

11. Use of the compounds of the formula I according to claim 1, and salts and solvates thereof, for the preparation of a medicament for the treatment and prophylaxis of diseases which can be influenced by the binding of the compounds of the formula I to 5 HT receptors.

12. Use of compounds of the formula I according to claim 1 and/or physiologically acceptable salts and solvates thereof for the preparation of a medicament having a 5-HT receptor-antagonistic action.

13. Use of compounds of the formula I according to claim 1 and/or physiologically acceptable salts and solvates thereof for the preparation of a medicament having a 5-HT_2A receptor-antagonistic action.

14. Pharmaceutical composition characterised by a content of at least one compound of the formula I according to claim 1 and/or one of its physiologically acceptable salts and/or one of its solvates.

15. Process for the preparation of pharmaceutical compositions, characterised in that a compound of the formula I according to claim 1 and/or one of its physiological acceptable salts and/or one of its solvates is converted into a suitable dosage form together with at least one solid, liquid or semi-liquid excipient or adjuvant.

16. Use of compounds of the formula claim 1 and/or physiologically acceptable salts or solvates thereof for the preparation of a medicament for the prophylaxis and/or treatment of psychoses, neurological disorders, amyotrophic lateral sclerosis, eating disorders, such as bulimia, anorexia nervosa, of premenstrual syndrome and/or for positively influencing obsessive-compulsive disorder (OCD).

17. Compounds of the formula I in which Het denotes one of the following radicals: