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- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20120302564
- Publication Date: November 29, 2012
- Appl. No: 13/361002
- Application Filed: January 30, 2012
- Claim: 1-23. (canceled)
- Claim: 24. A compound of formula (I): [chemical expression included] or a pharmaceutically acceptable salt thereof; wherein: R1 is -phenyl, 2-pyridyl, 3-pyridyl or 4-pyridyl, in each case substituted with a substituent different from H in an ortho position of the linkage to the backbone structure and optionally substituted with further substituents different from H; R2 is hydrogen, C1-4 alkyl, optionally substituted with up to 2 halo atoms; R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, halogen, C1-4 alkyl, optionally substituted with up to 5 halo atoms or —OC1-2 (halo)alkyl, C3-8 cycloalkyl, optionally substituted with halo, —C1-2 (halo)alkyl or —OC1-2 (halo)alkyl, —CN, —OH, —OC1-4 alkyl, optionally substituted with up to 5 halo atoms or —OC1-2 (halo)alkyl, C3-8 cycloalkyl optionally substituted with halo, —C1-2 (halo)alkyl, or —OC1-2 (halo)alkyl, —O(CH2)n—R10, wherein n can be 1 or 2; R10 is a cyclic group which can be unsubstituted or substituted preferably up to 4 times by halogen, C1-4 alkyl, optionally substituted with up to 5, preferably up to 3 halogen atoms, or OC1-4 alkyl, optionally substituted with up to 5, preferably up to 3 halogen atoms, wherein the compound of formula (I) is not 1-(2-hydroxyphenyl)-4-methyl-(1,2,4)triazolo[4,3-a]quinoxaline, 1-(2-chlorophenyl)-4-methyl-(1,2,4)triazolo[4,3-a]quinoxaline, 1-(2-nitrophenyl)-4-methyl-(1,2,4)triazolo[4,3-a]quinoxaline, 1-(2-methoxyphenyl)-4-methyl-(1,2,4)triazolo[4,3-a]quinoxaline, 1-(5-amino-2-chlorophenyl)-4-methyl-(1,2,4)triazolo[4,3-a]quinoxaline, 1-(5-amino-2-methoxyphenyl)-4-methyl-(1,2,4)triazolo[4,3-a]quinoxaline, 1-(5-amino-2-methylphenyl)-4-methyl-(1,2,4)triazolo[4,3-a]quinoxaline, or 1-(2-hydroxy-3-methoxyphenyl)-4-methyl-(1,2,4)triazolo[4,3-a]quinoxaline.
- Claim: 25. The compound of claim 24, wherein R1 is substituted with 1 to 3 substituents R7, R8 and/or R9 different from U so that at least one of these substituents is in an ortho position of the attachment site to the backbone structure, wherein R7, R8, R9 are independently from each other representing halogen, NO2, —C1-6 alkyl, optionally substituted with up to 5 fluorine atoms, —OC4-6 alkyl, optionally substituted with up to 53 fluorine atoms, —SC1-6 alkyl, optionally substituted with up to 5 fluorine atoms, -phenyl which can be substituted with up to two halogen atoms or —CF3 groups, —O(CH2)n—R11, wherein n can be 0, 1, 2, 3 or 4 R11 represents if n=2, 3 or 4: —OH, —OC1-4 alkyl, —O(C═O)C1-4 alkyl, if n==0, 1, 2, 3 or 4: —C3-6 alkyl, a cyclic group, which is linked to O(CH2)n via a covalent bond or via —C(═O)—, —CH(OH)—, or —CH(halogen)-, wherein the cyclic group is preferably selected from phenyl, C3-8 (hetero)cycloalkyl, such as cyclopropyl, cyclobutyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl, pyran-4-yl, 2-pyridyl, 3-pyridyl, or 4-pyridyl.
- Claim: 26. The compound of claim 25, wherein R1 represents phenyl, which is substituted with 1, 2 or 3 substituents R7, R8 or R9 wherein at least one of these substituents is in an ortho position of the attachment site to the backbone structure, or wherein R1 is 2-pyridyl, 3 pyridyl or 4-pyridyl which is substituted with 1, 2 or 3 substituents R7, R8 or R9, wherein one of these substituents is in an ortho position of the attachment site of the backbone structure.
- Claim: 27. The compound of claim 24, where R1 represents phenyl which is substituted with halogen, particularly Cl, in position 2 and C1-6 alkoxy optionally substituted with OH or OCH3, particularly —OCH2CH2CH2OH, in position 3, 5 or 6, particularly in position 5, wherein phenyl is attached via position 1 to the backbone.
- Claim: 28. The compound of claim 24, wherein R2 represents methyl optionally substituted with up to 2 fluorine atoms.
- Claim: 29. The compound of claims 24, wherein R3 and R6 are H.
- Claim: 30. The compound of claim 24, wherein R4 and R5 are independently from each other representing hydrogen, —OH, halogen, —CH3, —CF3, —OCH3, —OCHF2, —OCF3, —O(CH2)n—R10, wherein n can be 1 or 2, and wherein R10 is as defined in claim 1.
- Claim: 31. The compound of claim 24, wherein R4 is H and R5 is different from H or wherein R4 is different from H and R5 is H.
- Claim: 32. The compound of claim 24, wherein R2 is CH3, and R4 is H and R5 is different from H or wherein R2 is CH3, R4 is different from H and R5 is H.
- Claim: 33. The compound of claim 25, wherein R7, R8, R9 are independently from each other representing halogen, —CH3 optionally substituted with up to 3 fluorine atoms, —OC1-6 alkyl, optionally substituted with up to 3 fluorine atoms or —(OCH2)n—R11, wherein n can be 1, 2, 3 or 4 and wherein is as defined in claim 2, and particularly —OCH2CH2CH2OH.
- Claim: 34. The compound of claim 24, wherein R10 represents phenyl or quinolin-2-yl, which can be substituted up to two times by halogen and/or —OCH3.
- Claim: 35. The compound of claim 25, wherein R11 represents if n=2, 3 or 4: —OH or —OCH3 and if n=0, 1, 2, 3 or 4: phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, [chemical expression included]
- Claim: 36. The compound of claim 24, as described in any one of the Examples 1-31, 34-106 and 107-111, particularly as described in Example 98, or a pharmaceutically acceptable salt thereof.
- Claim: 37. The compound of claim 24, which is (i) a PDE2 inhibitor, (ii) a PDE10 inhibitor, and/or (iii) a PDE2 and PDE10 inhibitor.
- Claim: 38. A method comprising administering to a subject having a disorder a pharmaceutically acceptable amount of a compound to treat the disorder, wherein the compound is of formula (I): [chemical expression included] or a pharmaceutically acceptable salt thereof; wherein: R1 is -phenyl, 2-pyridyl, 3-pyridyl or 4-pyridyl, in each case substituted with a substituent different from H in an ortho position of the linkage to the backbone structure and optionally substituted with further substituents different from H; R2 is hydrogen, C1-4 alkyl, optionally substituted with up to 2 halo atoms; R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, halogen, C1-4 alkyl, optionally substituted with up to 5 halo atoms or —OC1-2 (halo)alkyl, C3-8 cycloalkyl, optionally substituted with halo, —C1-2 (halo)alkyl or —OC1-2(halo)alkyl, —CN, —OH, —OC1-4 alkyl, optionally substituted with up to 5 halo atoms or —OC1-2 (halo)alkyl, C3-8 cycloalkyl optionally substituted with halo, —C1-2 (halo)alkyl, or —OC1-2 (halo)alkyl, —O(CH2)n—R10, wherein n can be 1 or 2; and R10 is a cyclic group which can be unsubstituted or substituted up to 4 times by halogen, C1-4alkyl, optionally substituted with up to 5 halogen atoms, or OC1-4 alkyl, optionally substituted with up to 5 halogen atoms.
- Claim: 39. A compound comprising a pharmaceutically acceptable carrier and a compound of formula (I): [chemical expression included] or a pharmaceutically acceptable salt thereof; wherein: R1 is -phenyl, 2-pyridyl, 3-pyridyl or 4-pyridyl, in each case substituted with a substituent different from H in an ortho position of the linkage to the backbone structure and optionally substituted with further substituents different from H; R2 is hydrogen, C1-4 alkyl, optionally substituted with up to 2 halo atoms; R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, halogen, C1-4 alkyl, optionally substituted with up to 5 halo atoms or —OC1-2 (halo)alkyl, C3-8 cycloalkyl, optionally substituted with halo, —C1-2 (halo)alkyl or —OC1-2 (halo)alkyl, —CN, —OH, —OC1-4 alkyl, optionally substituted with up to 5 halo atoms or —OC1-2 (halo)alkyl, C3-8 cycloalkyl optionally substituted with halo, —C2 (halo)alkyl, or —OC1-2 (halo)alkyl, —O(CH2), —R10, wherein n can be 1 or 2; and R10 is a cyclic group which can be unsubstituted or substituted up to 4 times by halogen, C1-4 alkyl, optionally substituted with up to 5 halogen atoms, or OC1-4 alkyl, optionally substituted with up to 5 halogen atoms for use together with a pharmaceutically acceptable carrier.
- Claim: 40. A composition comprising the compound of claim 24 and a further active ingredient.
- Claim: 41. The composition according to claim 40, wherein the further active agent is an NMDA modulating agent or an acetylcholine neurotransmitter modulating agent.
- Claim: 42. The method of claim 38, wherein the disorder is associated with at least one of PDE2 or 10 hyperactivity and said pharmaceutically effective amount is sufficient to treat said disorder.
- Claim: 43. The method of claim 38, wherein the disorder is selected from the group consisting of a nervous central system disorder, obesity, type II diabetes, a metabolic syndrome, glucose intolerance, a neurologic disorder; and a psychiatric disorder.
- Claim: 44. The method of claim 38, wherein the disorder is (1) characterized by a symptom of cognitive deficiency in a mammal; (2) an organic mental disorder; (3) mental retardation; (4) an affective disorder; (5) a neurotic, stress-related and somatoform disorder; (6) a behavioral disorder and emotional disorders with onset usually occurring in childhood and adolescence, attention deficit hyperactivity syndrome (ADHD); (7) a disorder of psychological development, developmental disorders of scholastic skills; (8) schizophrenia and other psychotic disorder; (9) a disorder of adult personality and behavior; (10) a mental and behavioral disorders due to psychoactive substance use; (11) an extrapyramidal and movement disorder; (12) an episodic and paroxysmal disorders, epilepsy; (13) a systemic atrophies primarily affecting the central nervous system, ataxia; (14) a behavioral syndrome associated with physiological disturbances and physical factors; (15) a sexual dysfunction comprising excessive sexual drive; and (16) a factitious disorder.
- Claim: 45. The method of claim 44, wherein the disorder is Alzheimer's disease.
- Claim: 46. A method of treating disorders associated with hyperactivity of at least one of PDE2 or 10 comprising administering to a patient in need thereof the compound of claim 39.
- Current U.S. Class: 5142/332
- Current International Class: 61; 61; 61; 61; 61; 61; 61; 61; 07; 61
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