5-(Phenylisoxazolylethoxy) - Triazol- 3 -Yl Substituted Pyridine Compounds for the Treatment of Neurological, Psychiatric or Pain Disorders
The present invention is directed to novel compounds of formula (I)/(II)/(III), their use in therapy and pharmaceutical compositions comprising said novel compounds.
1 . A compound of formula I
as well as pharmaceutically acceptable salts, hydrates, isoforms and/or enantiomers thereof.
2 . A compound according to claim 1 , wherein the compound is the S-enantiomer.
3 . A compound according to claim 1 , wherein the compound is the R-enantiomer.
4 . A compound of formula II
as well as pharmaceutically acceptable salts, hydrates and/or isoforms thereof.
5 . A compound of formula III
as well as pharmaceutically acceptable salts, hydrates and/or isoforms thereof.
6 . A compound according to any one of claims 1 - 5 in crystalline form.
7 . A hydrochloride salt of a compound according to any one of claims 1 - 5 .
8 . A sulphate salt of a compound according to any one of claims 1 - 5 .
9 . A salt selected from 4-(5-{(1R)-1-[5-(3-chlorophenyl)isoxazol-3-yl]ethoxy}-4-methyl-4H-1,2,4-triazol-3-yl)pyridine hydrochloride and 4-(5-{(1R)-1-[5-(3-chlorophenyl)isoxazol-3-yl]ethoxy}-4-methyl-4H-1,2,4-triazol-3-yl)pyridine sulphate.
10 . A compound according to any one of claims 1 - 9 for use in therapy.
11 . A pharmaceutical composition comprising a compound according to any one of claims 1 - 9 as an active ingredient, together with a pharmacologically and pharmaceutically acceptable carrier.
12 . Use of a compound according to any one of claims 1 - 9 , or a pharmaceutically acceptable salt or an optical isomer thereof, for the manufacture of a medicament for the treatment of a mGluR5 receptor-mediated disorder.
13 . Use according to claim 12 , wherein said disorder is a neurological disorder.
14 . Use according to claim 12 , wherein said disorder is a psychiatric disorder.
15 . Use according to claim 12 , wherein said disorder is a gastrointestinal disorder.
16 . Use according to claim 12 , wherein said disorder is any one of gastroesophageal reflux disease, IBS, functional dyspepsia, cough, obesity, Alzheimer's disease, senile dementia, AIDS-induced dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's Chorea, migraine, epilepsy, schizophrenia, depression, anxiety, acute anxiety, obsessive compulsive disorder, ophthalmological disorders such as retinopathies, diabetic retinopathies, glaucoma, auditory neuropathic disorders such as tinnitus, chemotherapy induced neuropathies, post-herpetic neuralgia and trigeminal neuralgia, tolerance, dependency, addiction and craving disorders, neurodevelopmental disorders including Fragile X, autism, mental retardation, schizophrenia and Down's Syndrome, pain related to migraine, inflammatory pain, neuropathic pain disorders such as diabetic neuropathies, arthritis and rheumatitiod diseases, low back pain, post-operative pain, pain associated with various conditions including angina, renal or billiary colic, menstruation, migraine and gout; stroke, head trauma, anoxic and ischemic injuries, hypoglycemia, cardiovascular diseases and epilepsy.
17 . Use according to claim 16 , wherein said disorder is a chronic pain disorder.
18 . Use according to claim 16 , wherein said disorder is an acute pain disorder.
19 . Use according to claim 16 , wherein said disorder is anxiety.
20 . Use according to claim 16 , wherein said disorder is depression.
21 . Use according to claim 16 , wherein said disorder is Parkinson's disease.
22 . Use according to claim 16 , wherein said pain disorder is a neuropathic pain disorder.
23 . Use according to claim 16 , wherein said pain disorder is migraine.
24 . Use according to claim 16 , wherein said pain disorder is inflammatory pain.
25 . Use according to claim 16 , wherein said disorder is gastroesophageal reflux disease.
26 . Use according to claim 16 , wherein said disorder is cough.
27 . A method for the treatment or prevention of a mGluR5 receptor-mediated disorder, wherein an effective amount of a compound according to any one of claims 1 - 9 is administered to a subject in need of such treatment or prevention.
28 . A method according to claim 27 , wherein said disorder is a neurological disorder.
29 . A method according to claim 27 , wherein said disorder is a psychiatric disorder.
30 . A method according to claim 27 , wherein said disorder is any one of gastroesophageal reflux disease, IBS, functional dyspepsia, cough, obesity, Alzheimer's disease, senile dementia, AIDS-induced dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's Chorea, migraine, epilepsy, schizophrenia, depression, anxiety, acute anxiety, obsessive compulsive disorder, ophthalmological disorders such as retinopathies, diabetic retinopathies, glaucoma, auditory neuropathic disorders such as tinnitus, chemotherapy induced neuropathies, post-herpetic neuralgia and trigeminal neuralgia, tolerance, dependency, addiction and craving disorders, neurodevelopmental disorders including Fragile X, autism, mental retardation, schizophrenia and Down's Syndrome, pain related to migraine, inflammatory pain, neuropathic pain disorders such as diabetic neuropathies, arthritis and rheumatitiod diseases, low back pain, post-operative pain, pain associated with various conditions including angina, renal or billiary colic, menstruation, migraine and gout; stroke, head trauma, anoxic and ischemic injuries, hypoglycemia, cardiovascular diseases and epilepsy.
31 . A method according to claim 30 , wherein said disorder is a chronic pain disorder.
32 . A method according to claim 30 , wherein said disorder is an acute pain disorder.
33 . A method according to claim 30 , wherein said disorder is anxiety.
34 . A method according to claim 30 , wherein said disorder is depression.
35 . A method according to claim 30 , wherein said disorder is Parkinson's disease.
36 . A method according to claim 30 , wherein said pain disorder is a neuropathic pain disorder.
37 . A method according to claim 30 , wherein said pain disorder is migraine.
38 . A method according to claim 30 , wherein said pain disorder is inflammatory pain.
39 . A method according to claim 30 , wherein said disorder is gastroesophageal reflux disease.
40 . A method according to claim 30 , wherein said disorder is cough.