RU2007119310A - Enantiomers of 3-heteroaryl-8-azabicyclo- (3.2.1) -Oct-2-ena and their use as reverse capture inhibitors of monoamine neurotransmitters - Google Patents

Claims (14)

1. Enantiomerically pure compound of the formula I

or a pharmaceutically acceptable salt thereof, where R represents hydrogen or alkyl, wherein the alkyl is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; and Q represents a heteroaryl group, wherein the heteroaryl group is optionally substituted with one or more substituents independently selected from the group consisting of: halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, alkoxy, cycloalkoxy, alkoxyalkyl, cycloalkoxyalkyl, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, -NR'R ", - (C = O) NR′R ′ ′” or -NR ′ (C = O) R ′ ′; where R ′ and R ″ independently of each other represent hydrogen or alkyl. 2. The chemical compound according to claim 1, where R represents hydrogen or alkyl. 3. The chemical compound according to claim 1 or 2, where Q is benzothienyl. 4. The chemical compound according to claim 1 or 2, where Q is benzothienyl substituted with halogen. 5. The chemical compound according to claim 1, which is an enantiomerically pure compound of 3- (2-benzothienyl) -8H-8-azabicyclo [3.2.1] oct-2-ene or a pharmaceutically acceptable salt thereof. 6. The chemical compound according to claim 1, which is an enantiomerically pure compound 3- (7-fluoro-benzo [b] thiophen-2-yl) -8-aza-bicyclo [3.2.1] oct-2-ene; 3- (7-chloro-benzo [b] thiophen-2-yl) -8-aza-bicyclo [3.2.1] oct-2-ene; 3- (2-benzothienyl) -8-methyl-8-azabicyclo [3.2.1] oct-2-ene; 3- (7-fluoro-benzo [b] thiophen-2-yl) -8-methyl-8-azabicyclo [3.2.1] oct-2-ene or a pharmaceutically acceptable salt thereof. 7. The chemical compound according to claim 1, which is enantiomerically pure (+) - 3- (2-benzothienyl) -8H-8-azabicyclo [3.2.1] oct-2-ene or a pharmaceutically acceptable salt thereof. 8. The chemical compound according to claim 1, which is enantiomerically pure (-) - 3- (2-benzothienyl) -8H-8-azabicyclo [3.2.1] oct-2-ene or a pharmaceutically acceptable salt thereof. 9. The chemical compound according to claim 1, which is a enantiomerically pure (+) - 3- (7-fluoro-benzo [b] thiophen-2-yl) -8-aza-bicyclo [3.2.1] oct-2-ene; enantiomerically pure (-) - 3- (7-fluoro-benzo [b] thiophen-2-yl) -8-aza-bicyclo [3.2.1] oct-2-ene; enantiomerically pure (-) - 3- (7-chloro-benzo [b] thiophen-2-yl) -8-aza-bicyclo [3.2.1] oct-2-ene; enantiomerically pure (-) - 3- (2-benzothienyl) -8-methyl-8-azabicyclo [3.2.1] oct-2-ene; enantiomerically pure (+) - 3- (2-benzothienyl) -8-methyl-8-azabicyclo [3.2.1] oct-2-ene; enantiomerically pure (+) - 3- (7-fluoro-benzo [b] thiophen-2-yl) -8-methyl-8-aza-bicyclo [3.2.1] oct-2-ene; enantiomerically pure (-) - 3- (7-fluoro-benzo [b] thiophen-2-yl) -8-methyl-8-aza-bicyclo [3.2.1] oct-2-ene; or a pharmaceutically acceptable salt thereof. 10. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, excipient or diluent. 11. The use of a chemical compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament. 12. The use according to claim 11 for the manufacture of a pharmaceutical composition for the treatment, prevention or reduction of symptoms of a disease, or disorder, or condition of a mammal, including humans, that are sensitive to inhibition of reuptake of monoamine neurotransmitters in the central nervous system. 13. The use according to claim 11, where the disease, disorder or condition is a mood disorder, depression, atypical depression, depression secondary to pain, major depressive disorder, dysthymic disorder, bipolar disorder, bipolar disorder type I, bipolar disorder II type, cyclothymic disorder, mood disorder caused by a general medical condition, substance-induced mood disorder, pseudodementia, Ganser syndrome, obsessive-compulsive anxiety disorder, panic disorder, panic disorder without agoraphobia, panic disorder with agoraphobia, agoraphobia without a history of panic disorder, panic attack, memory disorders, memory loss, attention deficit hyperactivity disorder, obesity, anxiety, generalized anxiety disorder, eating disorder, illness Parkinson's, parkinsonism, dementia, age-related dementia, senile dementia, Alzheimer's disease, dementia-acquired immunodeficiency syndrome complex, age-related p memory disorder, specific phobia, sociophobia, social anxiety disorder, post-traumatic stress disorder, acute stress disorder, addiction to drugs, drug abuse, cocaine abuse, nicotine abuse, tobacco abuse, chronic alcoholism, alcoholism, kleptomania, pain, chronic pain, inflammatory pain, neuropathic pain, migraine pain, tension-type headache, chronic tension headache, more associated with depression, fibromyalgia, arthritis, osteoarthritis, rheumatoid arthritis, back pain, cancer pain, irritable bowel pain, irritable bowel syndrome, postoperative pain, pain after mastectomy (PMPS), pain after stroke, drug-induced neuropathy drugs, diabetic neuropathy, sympathetically supported pain, trigeminal neuralgia, toothache, myofascial pain, phantom pain, bulimia, premenstrual syndrome, premenstrual dysphoric disorder, syndrome p luteal phase, post-traumatic syndrome, chronic fatigue syndrome, urinary incontinence, stress urinary incontinence, urinary incontinence, bedwetting, premature ejaculation, erection problems, erectile dysfunction, premature female orgasm, legless leg syndrome (rest ), periodic limb movement syndrome, eating disorders, anorexia nervosa, sleep disorders, general developmental disorders, autism, Asperger's disorder, Rett's disorder, children's disintegration obstructive disorder, learning disability, motor skills disorder, mutism, trichotillomania, narcolepsy, depression after a stroke, brain damage caused by a stroke, neuronal damage caused by a stroke, or Gilles de la Tourette’s disease. 14. A method of treating, preventing or reducing the symptoms of a disease, or disorder, or condition in a living organism of an animal, including humans, that are sensitive to inhibition of reuptake of monoamine neurotransmitters in the central nervous system, comprising the step of introducing into the living organism an animal in need of this, a therapeutically effective amount of a compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof.