Hexahydrodiazepinoquinolines carrying a substituted alkyl radical

Abstract

The present invention relates to tricyclic hexahydrodiazepinoquinolines carrying a substituted alkyl radical, to a method for producing them, to a pharmaceutical composition containing such compounds, to their use as modulators, especially agonists or partial agonists, of the 5-HT 2C receptor, their use for preparing a medicament for the prevention or treatment of conditions and disorders which respond to the modulation of 5-HT 2C receptor, to a method for preventing or treating conditions and disorders which respond to the modulation of 5-HT 2C receptor, and processes for preparing such compounds and compositions.

1 .- 39 . (canceled) 
     
     
         40 . A method for treating disorders which respond to the modulation of the 5-HT 2c  receptor comprising
 administering to a subject in need thereof at least one compound of formula (I)   
       
         
           
           
               
               
           
         
         wherein 
         R 1  is selected from the group consisting of hydrogen, cyano, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, —C(═O)R 9 , phenyl, phenyl-C 1 -C 2 -alkyl and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO and SO 2  and optionally also 1 or 2 C═O and/or C═S groups as ring members, where the cyclic moieties in the three last-mentioned radicals may be substituted with one or more substituents R 10 ; 
         each R 2  is independently selected from the group consisting of cyano, nitro, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, fluorinated C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, —CH 2 NR 11a R 11b , —C(═O)R 9 ,
 phenyl, phenyl-C 1 -C 2 -alkyl, and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO 2 , C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R 10 ; or 
 two radicals R 2  bound to the same carbon atom, together with the carbon atom they are bound to, form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring, where the ring may contain 1, 2, 3 or 4 heteroatoms or heteroatom-containing groups selected from O, S, N, SO, SO 2 , C═O and C═S as ring members, and where the ring may be substituted with one or more substituents R 10 ; 
 
         R 3a  and R 3b , independently of each other, are selected from the group consisting of hydrogen, cyano, nitro, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, fluorinated C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl,
 —CH 2 NR 11a R 11b , —C(═O)R 9 , phenyl, phenyl-C 1 -C 2 -alkyl, and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO 2 , C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R 10 ; 
 
         R 4a  and R 4b , independently of each other, are selected from the group consisting of hydrogen, cyano, nitro, C 1 -C6-alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, fluorinated C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl,
 —CH 2 NR 11a R 11b , —C(═O)R 9 , phenyl, phenyl-C 1 -C 2 -alkyl, and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO 2 , C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R 10 ; or 
 R 4a  and R 4b  form together a group ═O or ═S; or 
 R 4a  and R 4b , together with the carbon atom they are bound to, form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring, where the ring may contain 1, 2, 3 or 4 heteroatoms or heteroatom-containing groups selected from O, S, N, SO, SO 2 , C═O and C═S as ring members, and where the ring may be substituted with one or more substituents R 10 ; 
 
         R 5a  and R 5b , independently of each other, are selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxyl, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, fluorinated C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, —NR 11a R 11b , —CH 2 NR 11a R 11b , —NR 11a C(O)R 9 ,
 —C(═O)R 9 , SO 2 NR 11a R 11b , C 1 -C 6 -alkylcarbonyloxy, fluorinated C 1 -C 6 -alkylcarbonyloxy, phenyl, phenyl-C 1 -C 2 -alkyl, phenoxy, phenylsulfonyl, benzyloxy and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO 2 , C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R 10 ; where R 5a  and R 5b  are not simultaneously hydroxyl; or 
 R 5a  and R 5b , together with the carbon atom they are bound to, form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring, where the ring may contain 1, 2, 3 or 4 heteroatoms or heteroatom-containing groups selected from O, S, N, SO, SO 2 , C═O and C═S as ring members, and where the ring may be substituted with one or more substituents R 10 ; 
 
         R 6  is C 1 -C 6 -alkyl which carries one or more substituents R 8 ; 
         each R 7  is independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkenyl, fluorinated C 3 -C 8 -cycloalkenyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, fluorinated C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, —NR 11a R 11b , —CH 2 NR 11a R 11b , —NR 11a C(O)R 9 , —C(═O)R 9 , SO 2 NR 11a R 11b , C 1 -C 6 -alkylcarbonyloxy, fluorinated C 1 -C 6 -alkylcarbonyloxy, phenyl, phenyl-C 1 -C 2 -alkyl, phenoxy, phenylsulfonyl, benzyloxy and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO 2 , C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R 10 ; or
 two radicals R 7  bound on neighboring carbon atoms, together with the carbon atoms they are bound to, form a 3-, 4-, 5-, 6-, 7- or 8-membered partially unsaturated or maximally unsaturated ring, where the ring may contain 1, 2, 3 or 4 heteroatoms or heteroatom-containing groups selected from O, S, N, SO, SO 2 , C═O and C═S as ring members, and where the ring may be substituted with one or more substituents R 10 ; 
 
         each R 8  is independently selected from the group consisting of hydroxyl, halogen, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl and —NR 11a R 11b ; 
         each R 9  is independently selected from the group consisting of hydrogen, cyano, hydroxyl, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, —NR 11a R 11b , —CH 2 NR 11a R 11b , phenyl, phenyl-C 1 -C 2 -alkyl, phenoxy, benzyloxy and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO 2 , C═O and C═S as ring members, where the cyclic moieties in the five last-mentioned radicals may be substituted with one or more substituents R 10 ; 
         each R 10  is independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, fluorinated C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, —COOH, —NR 11a R 11b , —CH 2 NR 11a R 11b , C 1 -C 6 -alkylcarbonyl, fluorinated C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, fluorinated C 1 -C 6 -alkoxycarbonyl, SO 2 NR 11a R 11b , C 1 -C 6 -alkylcarbonyloxy and fluorinated C 1 -C 6 -alkylcarbonyloxy;
 or two radicals R 10 , together with the atom(s) they are bound to, form a saturated, partially unsaturated or maximally unsaturated 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring, where the heterocyclic ring contains 1, 2 or 3 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO 2 , C═O and C═S as ring members; 
 
         R 11a  and R 11b , independently of each other and independently of each occurrence, are selected from the group consisting of hydrogen, cyano, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkylcarbonyl, fluorinated C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, fluorinated C 1 -C 6 -alkoxycarbonyl, phenyl and benzyl, where the phenyl moieties in the two last-mentioned radicals may carry 1, 2 or 3 substituents selected from halogen, cyano nitro, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy and fluorinated C 1 -C 6 -alkoxy; or,
 if R 11a  and R 11b  are bound to the same nitrogen atom, together with this nitrogen atom may form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring, where the ring may further contain 1, 2, 3 or 4 heteroatoms or heteroatom-containing groups selected from O, S, N, SO, SO 2 , C═O and C═S as ring members, and where the ring may be substituted with one or more substituents selected from halogen, cyano nitro, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy and fluorinated C 1 -C 6 -alkoxy; 
 
         a is 0, 1 or 2; and 
         b is 0, 1, 2 or 3;
 or an N-oxide, a tautomeric form, a stereoisomer or a pharmaceutically acceptable salt thereof. 
 
       
     
     
         41 . The method as claimed in  claim 40 , where the disorders are selected from the group consisting of damage of the central nervous system, disorders of the central nervous system, eating disorders, ocular hypertension, cardiovascular disorders, gastrointestinal disorders and diabetes. 
     
     
         42 . The method as claimed in  claim 41 , where the disorders are selected from the group consisting of bipolar disorder, depression, atypical depression, mood episodes, adjustment disorders, anxiety, panic disorders, post-traumatic syndrome, psychoses, schizophrenia, cognitive deficits of schizophrenia, memory loss, dementia of aging, Alzheimer's disease, neuropsychiatric symptoms in Alzheimer's disease, behavioral disorders associated with dementia, social phobia, mental disorders in childhood, attention deficit hyperactivity disorder, organic mental disorders, autism, mutism, disruptive behavior disorder, impulse control disorder, borderline personality disorder, obsessive compulsive disorder, migraine and other conditions associated with cephalic pain or other pain, raised intracranial pressure, seizure disorders, epilepsy, substance use disorders, alcohol abuse, cocaine abuse, tobacco abuse, smoking cessation, sexual dysfunction/erectile dysfunction in males, sexual dysfunction in females, premenstrual syndrome, late luteal phase syndrome, chronic fatigue syndrome, sleep disorders, sleep apnoea, chronic fatigue syndrome, psoriasis, Parkinson's disease, psychosis in Parkinson's disease, neuropsychiatric symptoms in Parkinson's disease, Lewy Body dementia, neuropsychiatric symptoms in Lewy Body dementia, spinal cord injury, trauma, stroke, pain, bladder dysfunction/urinary incontinence, encephalitis, meningitis, eating disorders, obesity, bulimia, weight loss, anorexia nervosa, ocular hypertension, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, diabetes mellitus, type I diabetes, type II diabetes, type III diabetes, diabetes secondary to pancreatic diseases, diabetes related to steroid use, diabetes complications, hyperglycemia and insulin resistance. 
     
     
         43 . The method as claimed in  claim 42 , where the disorders are selected from the group consisting of schizophrenia, depression, bipolar disorders, obesity, substance use disorders, neuropsychiatric symptoms in Alzheimer's disease and neuropsychiatric symptoms in Parkinson's disease. 
     
     
         44 . The method as claimed in  claim 40 , where R 1  is hydrogen. 
     
     
         45 . The method as claimed in  claim 40 , where R 2  is selected from methyl and CF 3 . 
     
     
         46 . The method as claimed in  claim 40 , where R 3a  and R 3b  are hydrogen. 
     
     
         47 . The method as claimed in  claim 40 , where R 4a  and R 4b  are hydrogen. 
     
     
         48 . The method as claimed in  claim 40 , where R 5a  is hydrogen or methyl and R 5b  is hydrogen 
     
     
         49 . The method as claimed in  claim 40 , where each R 8  is independently selected from the group consisting of halogen, C 1 -C 6 -alkoxy and fluorinated C 1 -C 6 -alkoxy. 
     
     
         50 . The method as claimed in  claim 40 , where R 6  is fluorinated C 1 -C 2 -alkyl. 
     
     
         51 . The method as claimed in  claim 40 , where R 6  is fluorinated methyl. 
     
     
         52 . The method as claimed in  claim 40 , where R 6  is CHF 2  or CF 3 . 
     
     
         53 . The method as claimed in  claim 40 , where R 6  is C 1 -C 4 -alkoxy-methyl. 
     
     
         54 . The method as claimed in  claim 40 , where R 6  is C 1 -C 4 -alkyl which carries a hydroxyl substituent. 
     
     
         55 . The method as claimed in  claim 40 , where a is 0 or 1. 
     
     
         56 . The method as claimed in  claim 40 , where in case that a is 1, R 2  is bound in β-position to the nitrogen ring atom carrying R 1 . 
     
     
         57 . The method as claimed in  claim 40 , where b is 0 or 1. 
     
     
         58 . The method as claimed in  claim 40 , wherein the at least one compound of formula (I) is at least one compound of formula (I1.1) 
       
         
           
           
               
               
           
         
         where
 R 7a  is H, Cl, F or methyl; 
 a is 0 or 1; and 
 R 2 , R 6 , R 7  and b are as defined as in  claim 40 . 
 
       
     
     
         59 . A method for treating disorders which respond to the modulation of the 5-HT 2c  receptor comprising administering to a subject in need thereof at least one compound selected from the group consisting of
 8-(Trifluoromethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   (S)-8-(Trifluoromethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   (R)-8-(Trifluoromethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   8-(2,2,2-Trifluoroethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   (S)-8-(2,2,2-Trifluoroethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   (R)-8-(2,2,2-Trifluoroethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   8-(Difluoromethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   (S)-8-(Difluoromethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   (R)-8-(Difluoromethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   4-Methyl-8-(trifluoromethyl)-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   8-(Difluoromethyl)-4-methyl-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   (4-Methyl-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinolin-8-yl)methanol;   8-(Fluoromethyl)-4-methyl-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   8-(Ethoxymethyl)-4-methyl-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline; and   8-(Methoxymethyl)-4-methyl-2,3,4,6,7,8-hexahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline;   and stereoisomers and pharmaceutically acceptable salts thereof.   
     
     
         60 . The method as claims in  claim 59 , where the disorders are selected from the group consisting of damage of the central nervous system, disorders of the central nervous system, eating disorders, ocular hypertension, cardiovascular disorders, gastrointestinal disorders and diabetes. 
     
     
         61 . The method as claims in  claim 60 , where the disorders are selected from the group consisting of bipolar disorder, depression, atypical depression, mood episodes, adjustment disorders, anxiety, panic disorders, post-traumatic syndrome, psychoses, schizophrenia, cognitive deficits of schizophrenia, memory loss, dementia of aging, Alzheimer's disease, neuropsychiatric symptoms in Alzheimer's disease, behavioral disorders associated with dementia, social phobia, mental disorders in childhood, attention deficit hyperactivity disorder, organic mental disorders, autism, mutism, disruptive behavior disorder, impulse control disorder, borderline personality disorder, obsessive compulsive disorder, migraine and other conditions associated with cephalic pain or other pain, raised intracranial pressure, seizure disorders, epilepsy, substance use disorders, alcohol abuse, cocaine abuse, tobacco abuse, smoking cessation, sexual dysfunction/erectile dysfunction in males, sexual dysfunction in females, premenstrual syndrome, late luteal phase syndrome, chronic fatigue syndrome, sleep disorders, sleep apnoea, chronic fatigue syndrome, psoriasis, Parkinson's disease, psychosis in Parkinson's disease, neuropsychiatric symptoms in Parkinson's disease, Lewy Body dementia, neuropsychiatric symptoms in Lewy Body dementia, spinal cord injury, trauma, stroke, pain, bladder dysfunction/urinary incontinence, encephalitis, meningitis, eating disorders, obesity, bulimia, weight loss, anorexia nervosa, ocular hypertension, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, diabetes mellitus, type I diabetes, type II diabetes, type III diabetes, diabetes secondary to pancreatic diseases, diabetes related to steroid use, diabetes complications, hyperglycemia and insulin resistance. 
     
     
         62 . The method as claimed in  claim 61 , where the disorders are selected from the group consisting of schizophrenia, depression, bipolar disorders, obesity, substance use disorders, neuropsychiatric symptoms in Alzheimer's disease and neuropsychiatric symptoms in Parkinson's disease.