Aryl- and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin

Abstract

The compounds of the present invention are represented by the following aryl- and heteroaryl-substituted tetrahydrobenzazepine and dihydrobenzazapine derivatives having formulae I(A-E) and formula (II): where the carbon atom designated * is in the R or S configuration, and the substituents X and R 1 -R 9 are as defined herein.

1 . A compound of formulae I(A-B) having the following structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 the carbon atom designated * is in the R or S configuration; and 
 X is an indolyl which is optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 R 1  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, each of which is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 2  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, each of which is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 2  is gem-dimethyl; 
 R 3 , R 5 , and R 6  are each independently selected from the group consisting of H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 3 , R 5 , and R 6  are each independently a 5- or 6-membered monocyclic carbocycle or heterocycle or a [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycle or heterocycle containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 R 4  is H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, wherein each of the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 4  is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 ; or 
 R 4  is a monocyclic or bicyclic aryl or heteroaryl selected from the group consisting of phenyl, pyridyl, 2-oxo-pyridin-1-yl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyranyl, furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, indanyl, indenyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl, indolinyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indazolyl, benzimidazolyl, benzooxazolyl, benzothiazolyl, benzoisoxazolyl, benzoisothiazolyl, benzotriazolyl, benzo[1,3]dioxolyl, naphthyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, 2,3-dihydro-benzo[1,4]dioxinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 4H-chromenyl, indolizinyl, quinolizinyl, 6aH-thieno[2,3-d]imidazolyl, 1H-pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, thieno[2,3-b]furanyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, furo[2,3-b]pyridinyl, furo[3,2-b]pyridinyl, thieno[3,2-d]pyrimidinyl, furo[3,2-d]pyrimidinyl, thieno[2,3-b]pyrazinyl, imidazo[1,2-a]pyrazinyl, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazinyl, 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazinyl, 2-oxo-2,3-dihydrobenzo[d]oxazolyl, 3,3-dimethyl-2-oxoindolinyl, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, benzo[c][1,2,5]oxadiazolyl, benzo[c][1,2,5]thiadiazolyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, and 3-oxo-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 provided that for compounds of formula IA, X is a substituted indolyl and R 4  is substituted monocyclic or bicyclic aryl or heteroaryl; and 
 provided that for compounds of formula IB, X is a substituted indolyl and R 4  is H, —OR 12 , —S(O) n R 13 , —C(O)R 13 , —NR 10 R 11 , —CN, halogen, or C 1 -C 6  alkyl, wherein each of the C 1 -C 6  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 7  is selected from the group consisting of H, —S(O) n R 13 , —C(O)R 13 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 8  is selected from the group consisting of H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 7  and R 8  are gem-dimethyl, with the proviso that only one of R 7  and R 8  is gem-dimethyl; 
 R 9  is H, halogen, —OR 12 , —SR 10 , C 1 -C 6  alkyl, —CN, or —NR 10 R 11 , wherein each of C 1 -C 6  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are each independently selected from the group consisting of H, —C(O)R 13 , C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are each independently selected from the group consisting of phenyl, benzyl, and other 5- or 6-membered monocyclic heterocycles, wherein each of the phenyl, benzyl, and 5- or 6-membered monocyclic heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R 14 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a saturated or partially saturated monocyclic or fused bicyclic heterocycle selected from the group consisting of piperidine, pyrrolidine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 3-oxomorpholino, 3-oxothiomorpholino, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, and other monocyclic or fused bicyclic heterocycles containing 1-4 heteroatoms selected from oxygen, nitrogen and sulfur, wherein the heterocycle is attached to the benzazepine core via the nitrogen atom, and is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 12 , —NR 12 R 13 , —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4-diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, wherein the heterocycle is optionally substituted on a ring carbon with from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 12 , —NR 12 R 13 , —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, or on the additional nitrogen atom from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4-diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, wherein the heterocycle is optionally substituted on the additional nitrogen atom with a substituent selected independently at each occurrence thereof from the group consisting of phenyl, benzyl, and 5- or 6-membered aromatic heterocycles containing 1-3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein each of the phenyl, benzyl, and 5- and 6-membered heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R 14 ; or 
 when R 4  is —NR 10 R 11  or —C(O)NR 10 R 11 , either R 10  or R 11  is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substituents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 , or either R 10  or R 11  is a C 1 -C 3  alkyl substituted with a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 ; 
 R 12  is selected from the group consisting of H, C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, C 4 -C 7  cycloalkylalkyl, and —C(O)R 13 , wherein each of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 13  is selected from the group consisting of H, —NR 10 R 11 , C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 12  and R 13  are each independently selected from the group consisting of phenyl, benzyl, pyridazinyl, pyrimidinyl, pyrazinyl, 5- or 6-membered aromatic monocyclic heterocycles, and [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycles or heterocycles containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; or 
 R 12  and R 13  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperidine, pyrrolidine, piperazine, 1,4-diazepane, morpholine, thiomorpholine, and other heterocycles containing 1-4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the heterocycle is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 10 , —S(O) n R 10 , —C(O)R 10 , —C(O)NR 10 R 11  and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 14  is independently selected at each occurrence from a substituent in the group consisting of halogen, —NO 2 , —OR 12 , —NR 10 R 11 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) n R 13 , —CN, —C(O)R 13 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; and 
 R 15  is independently selected at each occurrence from a substituent in the group consisting of —CN, halogen, C(O)R 13 , C 1 -C 3  alkyl, —OR 12 , —NR 10 R 11 , —S(O) n R 13 , aryl, and heteroaryl, wherein each of the aryl or heteroaryl groups is optionally substituted from 1 to 4 times with substituents as defined above in R 14 ; 
 n is 0, 1, or 2; 
 with the following provisos that (1) when R 4  is —S(O) n R 13 , n cannot be 0; and (2) when R 9  is a substituted alkyl, R 15  cannot be —NR 10 R 11    
 or an oxide thereof, or a pharmaceutically acceptable salt thereof. 
 
     
     
         2 . The compound according to  claim 1 , wherein X is a substituted indolyl and R 4  is substituted monocyclic or bicyclic aryl or heteroaryl. 
     
     
         3 . The compound according to  claim 1 , wherein X is a substituted indolyl and R 4  is selected from the group consisting of H, —OR 12 , —S(O) n R 13 , —C(O)R 13 , —NR 10 R 11 , —CN, —S(O) n R 13 , halogen, and C 1 -C 6  alkyl, wherein each of the C 1 -C 6  alkyl is optionally substituted from 1 to 3 times with substituents as defined in R 15 . 
     
     
         4 . The compound according to  claim 1 , wherein:
 X is an indolyl, optionally substituted from 1 to 4 times with substituents as defined in R 14 ;   R 1  is H, methyl, ethyl, or isopropyl;   R 2  is H, methyl, or gem-dimethyl;   R 3  is H, methyl, hydroxy, methoxy, fluoro, chloro, cyano, trifluoromethyl, or trifluoromethoxy;   R 5  is H, fluoro, chloro, methyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, or methoxy;   R 6  is H, fluoro, chloro, methyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, or methoxy;   R 7  is H, gem-dimethyl, or C 1 -C 4  alkyl, wherein each of the C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined in R 15 ;   R 8  is H, hydroxy, fluoro, chloro, C 1 -C 3  alkyl optionally substituted with hydroxyl or amino, or amino optionally substituted with C 1 -C 3  alkyl; and   R 9  is H, fluoro, chloro, methyl, hydroxyl, or cyano.   
     
     
         5 . The compound according to  claim 4 , wherein:
 R 4  is H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, wherein each of the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined in R 15 ; or   R 4  is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 .   
     
     
         6 . The compound according to  claim 4 , wherein R 4  is phenyl, pyridyl, 2-oxo-pyridin-1-yl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyranyl, furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, indanyl, indenyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl, indolinyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indazolyl, benzimidazolyl, benzooxazolyl, benzothiazolyl, benzoisoxazolyl, benzoisothiazolyl, benzotriazolyl, benzo[1,3]dioxolyl, naphthyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, 2,3-dihydro-benzo[1,4]dioxinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 4H-chromenyl, indolizinyl, quinolizinyl, 6aH-thieno[2,3-d]imidazolyl, 1H-pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, thieno[2,3-b]furanyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, furo[2,3-b]pyridinyl, furo[3,2-b]pyridinyl, thieno[3,2-d]pyrimidinyl, furo[3,2-d]pyrimidinyl, thieno[2,3-b]pyrazinyl, imidazo[1,2-a]pyrazinyl, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazinyl, 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazinyl, 2-oxo-2,3-dihydrobenzo[d]oxazolyl, 3,3-dimethyl-2-oxoindolinyl, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, benzo[c][1,2,5]oxadiazolyl, benzo[c][1,2,5]thiadiazolyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-a]pyrazinyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl, optionally substituted from 1 to 4 times with substituents as defined in R 14 . 
     
     
         7 . The compound according to  claim 1 , wherein the carbon atom designated * is in the R configuration. 
     
     
         8 . The compound according to  claim 1 , wherein the carbon atom designated * is in the S configuration. 
     
     
         9 . The compound according to  claim 1 , wherein the compound is a (+) stereoisomer. 
     
     
         10 . The compound according to  claim 1 , wherein the compound is a (−) stereoisomer. 
     
     
         11 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound according to  claim 1 . 
     
     
         12 . A method of treating a disorder which is created by or is dependent upon decreased availability of norepinephrine, dopamine, or serotonin, said method comprising:
 administering to a patient in need of such treatment a therapeutically effective amount of a compound according to  claim 1  or a pharmaceutically acceptable salt thereof.   
     
     
         13 . The method according to  claim 12 , further comprising:
 administering a therapeutically effective amount of a serotonin 1A receptor antagonist or a pharmaceutically acceptable salt thereof.   
     
     
         14 . The method according to  claim 13 , wherein the serotonin 1A receptor antagonist is WAY 100135 or spiperone. 
     
     
         15 . The method according to  claim 12 , further comprising:
 administering a therapeutically effective amount of a selective neurokinin-1 receptor antagonist or a pharmaceutically acceptable salt thereof.   
     
     
         16 . The method according to  claim 12 , further comprising:
 administering a therapeutically effective amount of a norepinephrine precursor or a pharmaceutically acceptable salt thereof.   
     
     
         17 . The method according to  claim 16 , wherein the norepinephrine precursor is L-tyrosine or L-phenylalanine. 
     
     
         18 . The method according to  claim 12 , wherein the disorder is selected from the group consisting of: lower back pain, attention deficit hyperactivity disorder (ADHD), cognition impairment, anxiety disorders, generalized anxiety disorder (GAD), panic disorder, bipolar disorder or manic depression or manic-depressive disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), acute stress disorder, social phobia, simple phobias, pre-menstrual dysphoric disorder (PMDD), social anxiety disorder (SAD), major depressive disorder (MDD), postnatal depression, dysthymia, depression associated with Alzheimer's disease, Parkinson's disease, or psychosis, supranuclear palsy, eating disorders, obesity, anorexia nervosa, bulimia nervosa, binge eating disorder, analgesia, substance abuse disorders, chemical dependencies, nicotine addiction, cocaine addiction, alcohol and amphetamine addiction, Lesch-Nyhan syndrome, neurodegenerative diseases, Parkinson's disease, late luteal phase syndrome or narcolepsy, psychiatric symptoms, anger, rejection sensitivity, movement disorders, extrapyramidal syndrome, Tic disorders, restless leg syndrome (RLS), tardive dyskinesia, supranuclear palsy, sleep related eating disorder (SRED), night eating syndrome (NES), stress urinary incontinence (SUI), migraine, neuropathic pain, diabetic neuropathy, fibromyalgia syndrome (FS), chronic fatigue syndrome (CFS), sexual dysfunction, premature ejaculation, male impotence, and thermoregulatory disorders. 
     
     
         19 . A compound of formula (II) having the following structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is an indolyl which is optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 R 1  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, each of which is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 2  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, each of which is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 2  is gem-dimethyl; 
 R 3 , R 5 , and R 6  are each independently selected from the group consisting of H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 3 , R 5 , and R 6  are each independently a 5- or 6-membered monocyclic carbocycle or heterocycle or a [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycle or heterocycle containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 R 4  is H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, wherein each of the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 4  is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 ; or 
 R 4  is phenyl, pyridyl, 2-oxo-pyridin-1-yl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyranyl, furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, indanyl, indenyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl, indolinyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indazolyl, benzimidazolyl, benzooxazolyl, benzothiazolyl, benzoisoxazolyl, benzoisothiazolyl, benzotriazolyl, benzo[1,3]dioxolyl, naphthyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, 2,3-dihydro-benzo[1,4]dioxinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 4H-chromenyl, indolizinyl, quinolizinyl, 6aH-thieno[2,3-d]imidazolyl, 1H-pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, thieno[2,3-b]furanyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, furo[2,3-b]pyridinyl, furo[3,2-b]pyridinyl, thieno[3,2-d]pyrimidinyl, furo[3,2-d]pyrimidinyl, thieno[2,3-b]pyrazinyl, imidazo[1,2-a]pyrazinyl, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazinyl, 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazinyl, 2-oxo-2,3-dihydrobenzo[d]oxazolyl, 3,3-dimethyl-2-oxoindolinyl, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, benzo[c][1,2,5]oxadiazolyl, benzo[c][1,2,5]thiadiazolyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, or 3-oxo-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 R 7  is selected from the group consisting of H, —S(O) n R 13 , —C(O)R 13 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 7  is gem-dimethyl; 
 R 8  is H or C 1 -C 6  alkyl, wherein each of C 1 -C 6  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are each independently selected from the group consisting of H, —C(O)R 13 , C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are each independently selected from the group consisting of phenyl, benzyl, and other 5- or 6-membered monocyclic heterocycles, wherein each of the phenyl, benzyl, and 5- or 6-membered monocyclic heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R 14 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a saturated or partially saturated monocyclic or fused bicyclic heterocycle selected from the group consisting of piperidine, pyrrolidine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 3-oxomorpholino, 3-oxothiomorpholino, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, and other monocyclic or fused bicyclic heterocycles containing 1-4 heteroatoms selected from oxygen, nitrogen and sulfur, wherein the heterocycle is attached to the benzazepine core via the nitrogen atom, and is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 12 , —NR 12 R 13 , —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4-diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, wherein the heterocycle is optionally substituted on a ring carbon with from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 12 , —NR 12 R 13 , —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, or on the additional nitrogen atom from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4-diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, wherein the heterocycle is optionally substituted on the additional nitrogen atom with a substituent selected independently at each occurrence thereof from the group consisting of phenyl, benzyl, and 5- or 6-membered aromatic heterocycles containing 1-3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein each of the phenyl, benzyl, and 5- and 6-membered heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R 14 ; or 
 when R 4  is —NR 10 R 11  or —C(O)NR 10 R 11 , either R 10  or R 11  is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substituents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and 
 —S(O) n R 13 , or either R 10  or R 11  is a C 1 -C 3  alkyl substituted with a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 ; 
 R 12  is selected from the group consisting of H, C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, C 4 -C 7  cycloalkylalkyl, and —C(O)R 13 , wherein each of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 13  is selected from the group consisting of H, —NR 10 R 11 , C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 12  and R 13  are each independently selected from the group consisting of phenyl, benzyl, pyridazinyl, pyrimidinyl, pyrazinyl, 5- or 6-membered aromatic monocyclic heterocycles, and [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycles or heterocycles containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; or 
 R 12  and R 13  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperidine, pyrrolidine, piperazine, 1,4-diazepane, morpholine, thiomorpholine, and other heterocycles containing 1-4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the heterocycle is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 10 , —S(O) n R 10 , —C(O)R 10 , —C(O)NR 10 R 11  and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 n is 0, 1, or 2; 
 R 14  is independently selected at each occurrence from a substituent in the group consisting of halogen, —NO 2 , —OR 12 , —NR 10 R 11 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) n R 13 , —CN, —C(O)R 13 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; and 
 R 15  is independently selected at each occurrence from a substituent in the group consisting of —CN, halogen, —C(O)R 13 , C 1 -C 3  alkyl, —OR 12 , —NR 10 R 11 , —S(O) n R 13 , aryl, and heteroaryl, wherein each of the aryl or heteroaryl groups is optionally substituted from 1 to 4 times with substituents as defined above in R 14 ; 
 with the proviso that when R 2  is a 2-(4-nitrophenoxy)ethyl, R 5  cannot be OC(O)NMe 2 ; 
 or an oxide thereof, or a pharmaceutically acceptable salt thereof. 
 
     
     
         20 . The compound according to  claim 19 , wherein:
 R 1  is H, methyl, ethyl, or isopropyl;   R 2  is H, methyl, or gem-dimethyl;   R 3  is H, methyl, hydroxy, methoxy, fluoro, chloro, cyano, trifluoromethyl, or trifluoromethoxy;   R 5  is H, fluoro, chloro, methyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, or methoxy;   R 6  is H, fluoro, chloro, methyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, or methoxy;   R 7  is H, gem-dimethyl, or C 1 -C 4  alkyl, wherein each of the C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined in R 15 ; and   R 8  is H or C 1 -C 3  alkyl.   
     
     
         21 . The compound according to  claim 19 , wherein the compound is a (+) stereoisomer. 
     
     
         22 . The compound according to  claim 19 , wherein the compound is a (−) stereoisomer. 
     
     
         23 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound according to  claim 19 . 
     
     
         24 . A method of treating a disorder which is created by or is dependent upon decreased availability of norepinephrine, dopamine, or serotonin, said method comprising:
 administering to a patient in need of such treatment a therapeutically effective amount of a compound according to  claim 19  or a pharmaceutically acceptable salt thereof.   
     
     
         25 . The method according to  claim 24 , further comprising:
 administering a therapeutically effective amount of a serotonin 1A receptor antagonist or a pharmaceutically acceptable salt thereof.   
     
     
         26 . The method according to  claim 25 , wherein the serotonin 1A receptor antagonist is WAY 100135 or spiperone. 
     
     
         27 . The method according to  claim 24 , further comprising:
 administering a therapeutically effective amount of a selective neurokinin-1 receptor antagonist or a pharmaceutically acceptable salt thereof.   
     
     
         28 . The method according to  claim 24 , further comprising:
 administering a therapeutically effective amount of a norepinephrine precursor or a pharmaceutically acceptable salt thereof.   
     
     
         29 . The method according to  claim 28 , wherein the norepinephrine precursor is L-tyrosine or L-phenylalanine. 
     
     
         30 . The method according to  claim 24 , wherein the disorder is selected from the group consisting of: lower back pain, attention deficit hyperactivity disorder (ADHD), cognition impairment, anxiety disorders, generalized anxiety disorder (GAD), panic disorder, bipolar disorder or manic depression or manic-depressive disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), acute stress disorder, social phobia, simple phobias, pre-menstrual dysphoric disorder (PMDD), social anxiety disorder (SAD), major depressive disorder (MDD), postnatal depression, dysthymia, depression associated with Alzheimer's disease, Parkinson's disease, or psychosis, supranuclear palsy, eating disorders, obesity, anorexia nervosa, bulimia nervosa, binge eating disorder, analgesia, substance abuse disorders, chemical dependencies, nicotine addiction, cocaine addiction, alcohol and amphetamine addiction, Lesch-Nyhan syndrome, neurodegenerative diseases, Parkinson's disease, late luteal phase syndrome or narcolepsy, psychiatric symptoms, anger, rejection sensitivity, movement disorders, extrapyramidal syndrome, Tic disorders, restless leg syndrome (RLS), tardive dyskinesia, supranuclear palsy, sleep related eating disorder (SRED), night eating syndrome (NES), stress urinary incontinence (SUI), migraine, neuropathic pain, diabetic neuropathy, fibromyalgia syndrome (FS), chronic fatigue syndrome (CFS), sexual dysfunction, premature ejaculation, male impotence, and thermoregulatory disorders. 
     
     
         31 . A process for preparation of a product compound of formulae I(A-B) having the following structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 the carbon atom designated * is in the R or S configuration; and 
 X is an indolyl which is optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 R 1  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, each of which is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 2  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, each of which is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 2  is gem-dimethyl; 
 R 3 , R 5 , and R 6  are each independently selected from the group consisting of H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 3 , R 5 , and R 6  are each independently a 5- or 6-membered monocyclic carbocycle or heterocycle or a [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycle or heterocycle containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 R 4  is H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, or C 4 -C 7  cycloalkylalkyl, wherein each of the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 4  is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 ; or 
 R 4  is a monocyclic or bicyclic aryl or heteroaryl selected from the group consisting of phenyl, pyridyl, 2-oxo-pyridin-1-yl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyranyl, furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, indanyl, indenyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl, indolinyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indazolyl, benzimidazolyl, benzooxazolyl, benzothiazolyl, benzoisoxazolyl, benzoisothiazolyl, benzotriazolyl, benzo[1,3]dioxolyl, naphthyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, 2,3-dihydro-benzo[1,4]dioxinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 4H-chromenyl, indolizinyl, quinolizinyl, 6aH-thieno[2,3-d]imidazolyl, 1H-pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, thieno[2,3-b]furanyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, furo[2,3-b]pyridinyl, furo[3,2-b]pyridinyl, thieno[3,2-d]pyrimidinyl, furo[3,2-d]pyrimidinyl, thieno[2,3-b]pyrazinyl, imidazo[1,2-a]pyrazinyl, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazinyl, 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazinyl, 2-oxo-2,3-dihydrobenzo[d]oxazolyl, 3,3-dimethyl-2-oxoindolinyl, 2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, benzo[c][1,2,5]oxadiazolyl, benzo[c][1,2,5]thiadiazolyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-a]pyrazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, and 3-oxo-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; 
 provided that for compounds of formula IA, X is a substituted indolyl and R 4  is substituted monocyclic or bicyclic aryl or heteroaryl; and 
 provided that for compounds of formula IB, X is a substituted indolyl and R 4  is H, —OR 12 , —S(O) n R 13 , —C(O)R 13 , —NR 10 R 11 , —CN, halogen, or C 1 -C 6  alkyl, wherein each of the C 1 -C 6  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 7  is selected from the group consisting of H, —S(O) n R 13 , —C(O)R 13 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 8  is selected from the group consisting of H, halogen, —OR 12 , —S(O) n R 13 , —CN, —C(O)R 13 , —NR 10 R 11 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 7  and R 8  are gem-dimethyl, with the proviso that only one of R 7  and R 8  is gem-dimethyl; 
 R 9  is H, halogen, —OR 12 , —SR 10 , C 1 -C 6  alkyl, —CN, or —NR 10 R 11 , wherein each of C 1 -C 6  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are each independently selected from the group consisting of H, —C(O)R 13 , C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are each independently selected from the group consisting of phenyl, benzyl, and other 5- or 6-membered monocyclic heterocycles, wherein each of the phenyl, benzyl, and 5- or 6-membered monocyclic heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R 14 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a saturated or partially saturated monocyclic or fused bicyclic heterocycle selected from the group consisting of piperidine, pyrrolidine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 3-oxomorpholino, 3-oxothiomorpholino, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, and other monocyclic or fused bicyclic heterocycles containing 1-4 heteroatoms selected from oxygen, nitrogen and sulfur, wherein the heterocycle is attached to the benzazepine core via the nitrogen atom, and is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 12 , —NR 12 R 13 , —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4-diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, wherein the heterocycle is optionally substituted on a ring carbon with from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 12 , —NR 12 R 13 , —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, or on the additional nitrogen atom from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of —S(O) n R 13 , —C(O)R 13 , and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 10  and R 11  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperazine, 2-oxopiperazinyl, 2-oxo-1,4-diazepanyl, 5-oxo-1,4-diazepanyl, 1,4-diazepane, and other heterocycles containing one additional nitrogen atom in the ring, wherein the heterocycle is optionally substituted on the additional nitrogen atom with a substituent selected independently at each occurrence thereof from the group consisting of phenyl, benzyl, and 5- or 6-membered aromatic heterocycles containing 1-3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein each of the phenyl, benzyl, and 5- and 6-membered heterocycle is optionally substituted from 1 to 3 times with substituents as defined below in R 14 ; or 
 when R 4  is —NR 10 R 11  or —C(O)NR 10 R 11 , either R 10  or R 11  is a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substituents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 , or either R 10  or R 11  is a C 1 -C 3  alkyl substituted with a bridged bicyclic ring containing 6-12 carbon atoms and optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the bridged bicyclic ring is optionally substituted from 1 to 3 times with substitutents selected from the group consisting of C 1 -C 3  alkyl, —C(O)R 13 , and —S(O) n R 13 ; 
 R 12  is selected from the group consisting of H, C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, C 4 -C 7  cycloalkylalkyl, and —C(O)R 13 , wherein each of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 R 13  is selected from the group consisting of H, —NR 10 R 11 , C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; or 
 R 12  and R 13  are each independently selected from the group consisting of phenyl, benzyl, pyridazinyl, pyrimidinyl, pyrazinyl, 5- or 6-membered aromatic monocyclic heterocycles, and [5,5]-, [6,5]-, [6,6]-, or [6,7]-fused bicyclic carbocycles or heterocycles containing 1-5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, optionally substituted from 1 to 4 times with substituents as defined below in R 14 ; or 
 R 12  and R 13  are taken together with the nitrogen to which they are attached to form a heterocycle selected from the group consisting of piperidine, pyrrolidine, piperazine, 1,4-diazepane, morpholine, thiomorpholine, and other heterocycles containing 1-4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein the heterocycle is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OR 10 , —S(O) n R 10 , —C(O)R 10 , —C(O)NR 10 R 11  and C 1 -C 4  alkyl, wherein each of C 1 -C 4  alkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; 
 n is 0, 1, or 2; 
 R 14  is independently selected at each occurrence from a substituent in the group consisting of halogen, —NO 2 , —OR 12 , —NR 10 R 11 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) n R 13 , —CN, —C(O)R 13 , C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl, wherein each of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 6  cycloalkyl, and C 4 -C 7  cycloalkylalkyl is optionally substituted from 1 to 3 times with substituents as defined below in R 15 ; and 
 R 15  is independently selected at each occurrence from a substituent in the group consisting of —CN, halogen, —C(O)R 13 , C 1 -C 3  alkyl, —OR 12 , —NR 10 R 11 , —S(O) n R 13 , aryl, and heteroaryl, wherein each of the aryl or heteroaryl groups is optionally substituted from 1 to 4 times with substituents as defined above in R 14 ; 
 with the following provisos that (1) when R 4  is —S(O) n R 13 , n cannot be 0; and (2) when R 9  is a substituted alkyl, R 15  cannot be —NR 10 R 11 ; 
 or an oxide thereof, or a pharmaceutically acceptable salt thereof, 
 said process comprising:
 treating an intermediate compound of the formula: 
 
 
       
         
           
           
               
               
           
         
       
       under conditions effective to produce the product compound.