التفاصيل البيبلوغرافية
| العنوان: |
NOVEL 1,4-DIAZA-BICYCLO[3.2.2]NONYL PYRIMIDINYL DERIVATIVES AND THEIR MEDICAL USE |
| Document Number: |
20090197872 |
| تاريخ النشر: |
August 6, 2009 |
| Appl. No: |
12/299108 |
| Application Filed: |
May 29, 2007 |
| مستخلص: |
This invention relates to novel 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivatives and their use in the manufacture of pharmaceutical compositions. The compounds of the invention are found to be cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances. |
| Inventors: |
Peters, Dan (Malmo, SE); Olsen, Gunnar M. (Smorum, DK); Nielsen, Elsebet Ostergaard (Kobenhavn, DK); Timmermann, Daniel B. (Herlev, DK); Loechel, Steven Charles (Frederiksberg, DK); Mikkelsen, Jens Damsgaard (Lyngby, DK); Hansen, Henrik Bjork (Kobenhavn, DK); Redrobe, John Paul (Rodovre, DK); Christensen, Jeppe Kejser (Kobenhavn, DK); Dyhring, Tino (Solrod, DK) |
| Claim: |
1-10. (canceled) |
| Claim: |
11. A 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidine derivative represented by Formula I [chemical expression included] or a pharmaceutically acceptable salt thereof; wherein X represents a single (covalent) bond (i.e. X is absent) or O; and Ar represents a monocyclic or bicyclic, carbocyclic or heterocyclic group, which monocyclic or bicyclic, carbocyclic or heterocyclic group may optionally be substituted one or more times with alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, carboxy, alkyl-carbonyl, alkoxy-carbonyl, alkyl-carbonyl-oxy, carbamoyl, amido, sulfamoyl, phenyl and/or benzyl. |
| Claim: |
12. The 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivative of claim 11, or a pharmaceutically acceptable salt thereof, wherein X represents a single (covalent) bond (i.e. X is absent) or O. |
| Claim: |
13. The 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivative of claim 11, or a pharmaceutically acceptable salt thereof, wherein Ar represents a monocyclic or bicyclic, carbocyclic or heterocyclic group, which monocyclic or bicyclic, carbocyclic or heterocyclic group may optionally be substituted one or two times with alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, carboxy, alkyl-carbonyl, alkoxy-carbonyl, alkyl-carbonyl-oxy, carbamoyl, amido, sulfamoyl, phenyl and/or benzyl. |
| Claim: |
14. The 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivative of claim 13, or a pharmaceutically acceptable salt thereof, wherein Ar represents phenyl, optionally substituted one or more times with alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, carboxy, alkyl-carbonyl, alkoxy-carbonyl, alkyl-carbonyl-oxy, carbamoyl, amido, sulfamoyl, phenyl and/or benzyl. |
| Claim: |
15. The 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivative of claim 13, or a pharmaceutically acceptable salt thereof, wherein Ar represents a monocyclic or bicyclic heterocyclic group selected from furanyl, thienyl, benzofuranyl and benzothienyl, optionally substituted one or more times with alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, halo, haloalkyl, haloalkoxy, cyano, nitro, amino, carboxy, alkyl-carbonyl, alkoxy-carbonyl, alkyl-carbonyl-oxy, carbamoyl, amido, sulfamoyl, phenyl and/or benzyl. |
| Claim: |
16. The 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivative of claim 11, which is [2-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-carbamic acid phenyl ester; N-[2-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-3-fluoro-benzamide; N-[2-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-3-methoxy-benzamide; N-[2-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-4-methoxy-benzamide; N-[2-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-4-fluoro-benzamide; Benzofuran-2-carboxylic acid [2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-amide; Furan-2-carboxylic acid [2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]amide; 5-Bromo-furan-2-carboxylic acid [2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-amide; Naphthalene-2-carboxylic acid [2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-amide; 4-Chloro-N-[2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-benzamide; 3-Chloro-N-[2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-5-yl]-benzamide; 4-Bromo-N-[2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-benzamide; 3-Bromo-N-[2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-benzamide; N-[2-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-2-methoxy-benzamide; or 2-Chloro-N-[2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-benzamide; or a pharmaceutically acceptable salt thereof. |
| Claim: |
17. A pharmaceutical composition comprising a therapeutically effective amount of the 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivative of claim 11, or a pharmaceutically-acceptable salt thereof, together with at least one pharmaceutically-acceptable carrier or diluent. |
| Claim: |
18. A method of treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, including a human, which disorder, disease or condition is responsive to modulation of cholinergic receptors and/or monoamine receptors, which method comprises the step of administering to such a living animal body in need thereof a therapeutically effective amount of the 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivative of claim 11 or a pharmaceutically acceptable salt thereof. |
| Claim: |
19. The method according to claim 18, wherein the disease, disorder or condition is a cognitive disorder, learning deficit, memory deficits and dysfunction, Down's syndrome, Alzheimer's disease, attention deficit, attention deficit hyperactivity disorder (ADHD), Tourette's syndrome, psychosis, depression, Bipolar Disorder, mania, manic depression, schizophrenia, cognitive or attention deficits related to schizophrenia, obsessive compulsive disorders (OCD), panic disorders, eating disorders such as anorexia nervosa, bulimia and obesity, narcolepsy, nociception, AIDS-dementia, senile dementia, autism, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, anxiety, non-OCD anxiety disorders, convulsive disorders, epilepsy, neurodegenerative disorders, transient anoxia, induced neuro-degeneration, neuropathy, diabetic neuropathy, peripheral dyslexia, tardive dyskinesia, hyperkinesia, mild pain, moderate or severe pain, pain of acute, chronic or recurrent character, pain caused by migraine, postoperative pain, phantom limb pain, inflammatory pain, neuropathic pain, chronic headache, central pain, pain related to diabetic neuropathy, to post therapeutic neuralgia, or to peripheral nerve injury, bulimia, post-traumatic syndrome, social phobia, sleeping disorders, pseudodementia, Ganser's syndrome, pre-menstrual syndrome, late luteal phase syndrome, fibromyalgia, chronic fatigue syndrome, mutism, trichotillomania, jet-lag, arrhythmias, smooth muscle contractions, angina pectoris, premature labour, diarrhoea, asthma, tardive dyskinesia, hyperkinesia, premature ejaculation, erectile difficulty, hypertension, inflammatory disorders, inflammatory skin disorders, acne, rosacea, Crohn's disease, inflammatory bowel disease, ulcerative colitis, diarrhoea, or withdrawal symptoms caused by termination of use of addictive substances, including nicotine containing products such as tobacco, opioids such as heroin, cocaine and morphine, benzodiazepines and benzodiazepine-like drugs, and alcohol. |
| Current U.S. Class: |
514/221 |
| Current International Class: |
61; 07; 61 |
| رقم الانضمام: |
edspap.20090197872 |
| قاعدة البيانات: |
USPTO Patent Applications |