Substituted pyrazole compounds

• US 20070010531A1
• Filed: 03/10/2004
• Published: 01/11/2007
• 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, Finsinger, Dirk, Bartoszyk, Gerd, Van Amsterdam, Christoph, Arlt, Michael
• Granted Patent: US 7,842,695 B2
• Time in Patent Office: Days
• US Class Current: 514/255.50
• 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 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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 231/40 Acylated on said nitrogen atom
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings

Abstract

Compounds of the formula (I) and salts and solvates thereof, in which X, R¹, R², R³, and R⁵ 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 R′

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, 3,4,5trifluorophenyl, 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 R³ denotes H.

4. Compounds of the formula I according to claim 1, in which R⁴ denotes H.

5. Compounds of the formula I according to claim 1, in which R² 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- or 2,6-difluoro- or -dicyanophenyl, thiophen-2yl 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, or 2- or 3-pyrazinyl.

6. Compounds of the formula I according to claim 1, in which X denotes 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-HT2A 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 physiologically 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 I according to 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 obsessivecompulsive disorder (OCD).

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