Aminotetraline and aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy

Abstract

The present invention relates to aminotetraline and aminoindane derivatives of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such aminotetraline and aminoindane derivatives, and the use of such aminotetraline and aminoindane derivatives for therapeutic purposes. The aminotetraline and aminoindane derivatives are GlyT1 inhibitors.

1 .- 19 . (canceled) 
     
     
         20 . A method for treating a neurologic or psychiatric disorder or pain in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         A is a 5- or 6-membered ring; 
         R 1  is hydrogen, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 6 -alkyl, tri-(C 1 -C 4 -alkyl)-silyl-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylcarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkyloxycarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylaminocarbonylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylaminocarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylsulfonylamino-C 1 -C 4 -alkyl, (optionally substituted C 6 -C 12 -aryl-C 1 -C 6 -alkyl)amino-C 1 -C 4 -alkyl, optionally substituted C 6 -C 12 -aryl-C 1 -C 4 -alkyl, optionally substituted M 3 -M 12 -heterocyclyl-C 1 -C 4 -alkyl, C 3 -C 12 -cycloalkyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, halogenated C 1 -C 6 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, aminocarbonyl, C 1 -C 6 -alkylaminocarbonyl, (halogenated C 1 -C 4 -alkyl)aminocarbonyl, C 6 -C 12 -arylaminocarbonyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkoxy, halogenated C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, amino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylamino-C 1 -C 4 -alkoxy, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylcarbonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -arylcarbonylamino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkoxycarbonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -aryl-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylsulfonylamino-C 1 -C 4 -alkoxy, (halogenated C 1 -C 6 -alkyl)sulfonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -arylsulfonylamino-C 1 -C 4 -alkoxy, (C 6 -C 12 -aryl-C 1 -C 6 -alkyl)sulfonylamino-C 1 -C 4 -alkoxy, M 3 -M 12 -heterocyclylsulfonylamino-C 1 -C 4 -alkoxy, M 3 -M 12 -heterocyclyl-C 1 -C 4 -alkoxy, C 6 -C 12 -aryloxy, M 3 -M 12 -heterocyclyloxy, C 1 -C 6 -alkylthio, halogenated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylamino, (halogenated C 1 -C 6 -alkyl)amino, di-C 1 -C 6 -alkylamino, di-(halogenated C 1 -C 6 -alkyl)amino, C 1 -C 6 -alkylcarbonylamino, (halogenated C 1 -C 6 -alkyl)carbonylamino, C 6 -C 12 -arylcarbonylamino, C 1 -C 6 -alkylsulfonylamino, (halogenated C 1 -C 6 -alkyl)sulfonylamino, C 6 -C 12 -arylsulfonylamino or optionally substituted M 3 -M 12 -heterocyclyl; 
         W is —NR 7 — or a bond; 
         A 1  is optionally substituted C 1 -C 4 -alkylene or a bond; 
         Q is —S(O) 2 — or —C(O)—; 
         Y is —NR 8 — or a bond; 
         n1 is 0, 1, 2, or 3; 
         n2 is 0, 1, 2, or 3; 
         X 1  is >N— or >CH—; 
         R 6  is hydrogen, halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, —CN, hydroxy, C 1 -C 6 -alkoxy or halogenated C 1 -C 6 -alkoxy, or two radicals R 6  together with the carbon atom to which they are attached form a carbonyl group; 
         R 2  is hydrogen, halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 4 -alkyl, —CN, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkoxy, halogenated C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxycarbonyl, C 2 -C 6 -alkenyloxy, C 6 -C 12 -aryl-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylcarbonyloxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, aminosulfonyl, amino, C 1 -C 6 -alkylamino, C 2 -C 6 -alkenylamino, nitro or optionally substituted M 3 -M 12 -heterocyclyl, or two radicals R 2  together with the ring atoms of A to which they are bound form a 5- or 6 membered ring; 
         m is 0 or 1; 
         R 3  is hydrogen, halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy, or two radicals R 3  together with the carbon atom to which they are attached form a carbonyl group; 
         Y 1  is a bond or optionally substituted C 1 -C 4 -alkylene; 
         R 4a  is hydrogen, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, —CH 2 CN, C 6 -C 12 -aryl-C 1 -C 4 -alkyl, optionally substituted C 3 -C 12 -cycloalkyl, —CHO, C 1 -C 4 -alkylcarbonyl, (halogenated C 1 -C 4 -alkyl)carbonyl, C 6 -C 12 -arylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, C 1 -C 6 -alkylaminocarbonyl, C 2 -C 6 -alkenyl, —C(═NH)NH 2 , —C(═NH)NHCN, C 1 -C 6 -alkylsulfonyl, C 6 -C 12 -arylsulfonyl, amino, —NO or optionally substituted M 3 -M 12 -heterocyclyl; or 
         R 4a  is optionally substituted C 1 -C 4 -alkylene that is bound to a carbon atom in Y 1 ; 
         R 4b  is hydrogen, C 1 -C 6 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, —CH 2 CN, —CHO, C 1 -C 4 -alkylcarbonyl, (halogenated C 1 -C 4 -alkyl)carbonyl, C 6 -C 12 -arylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, C 1 -C 6 -alkylaminocarbonyl, C 2 -C 6 -alkenyl, —C(═NH)NH 2 , —C(═NH)NHCN, C 1 -C 6 -alkylsulfonyl, C 6 -C 12 -arylsulfonyl, amino, —NO or M 3 -M 12 -heterocyclyl; or 
         R 4a , R 4b  
 together are optionally substituted C 2 -C 6 -alkylene, wherein one —CH 2 — of C 2 -C 6 -alkylene may be replaced by an oxygen atom or —NR 10 ; 
 
         X 2  is —O—, —NR 11a —, —S—, >CR 12a R 12b  or a bond; 
         X 3  is —O—, —NR 11b —, —S—, >CR 13a R 13b  or a bond; 
         R 5  is optionally substituted C 6 -C 12 -aryl, optionally substituted C 3 -C 12 -cycloalkyl or optionally substituted M 3 -M 12 -heterocyclyl; 
         R 7  is hydrogen or C 1 -C 6 -alkyl; 
         R 8  is hydrogen, C 1 -C 6 -alkyl, C 3 -C 32 -cycloalkyl, amino-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl-C 1 -C 4 -alkyl or M 3 -M 12 -heterocyclyl; or 
         R 8 , R 1  
 together are C 1 -C 4 -alkylene; 
 
         R 10  is hydrogen or C 1 -C 6 -alkyl; 
         R 11a  is hydrogen or C 1 -C 6 -alkyl; 
         R 11b  is hydrogen or C 1 -C 6 -alkyl; 
         R 12a  is hydrogen, optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, M 3 -M 12 -heterocyclyl-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl or hydroxy; 
         R 12b  is hydrogen or C 1 -C 6 -alkyl, or 
         R 12a , R 12b  
 together with the carbon atom to which they are attached form a carbonyl or are optionally substituted C 2 -C 4 -alkylene, wherein one —CH 2 — of C 2 -C 4 -alkylene may be replaced by an oxygen atom or —NR 14 —; 
 
         R 13a  is hydrogen, optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, M 3 -M 12 -heterocyclyl-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl or hydroxy; 
         R 13b  is hydrogen or C 1 -C 6 -alkyl, or 
         R 13a , R 13b  
 together with the carbon atom to which they are attached form a carbonyl or are optionally substituted C 1 -C 4 -alkylene, wherein one —CH 2 — of C 1 -C 4 -alkylene may be replaced by an oxygen atom or —NR 15 —; 
 
         R 14  is hydrogen or C 1 -C 6 -alkyl; and 
         R 15  is hydrogen or C 1 -C 6 -alkyl, 
         or a physiologically tolerated salt thereof. 
       
     
     
         21 . The method of  claim 20 , wherein A is a benzene ring or a ring selected from the group consisting of the following 5- or 6-membered heterocyclic rings: 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 20 , wherein R 1  is C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, or C 3 -C 12 -cycloalkyl. 
     
     
         23 . The method of  claim 20 , wherein W is a bond and A 1  is a bond. 
     
     
         24 . The method of  claim 20 , wherein Q is —S(O) 2 — and Y is —NR 8 —. 
     
     
         25 . The method of  claim 20 , wherein at least one of n1 and n2 is 1, 2, or 3 and the sum of n1+n2 is 2, 3, or 4. 
     
     
         26 . The method of  claim 20 , wherein X 1  is >N—, n1 is 1, and n2 is 1; or X 1  is >CH—, n1 is 1, and n2 is 1. 
     
     
         27 . The method of  claim 20 , wherein R 6  is hydrogen, C 1 -C 4 -alkyl, or two radicals R 6  together with the carbon atom to which they are attached form a carbonyl group. 
     
     
         28 . The method of  claim 20 , wherein the compound of formula (I) is 
       
         
           
           
               
               
           
         
       
     
     
         29 . The method of  claim 20 , wherein R 2  is hydrogen or halogen. 
     
     
         30 . The method of  claim 20 , wherein R 3  is hydrogen or C 1 -C 6 -alkyl. 
     
     
         31 . The method of  claim 20 , wherein Y 1  is a bond. 
     
     
         32 . The method of  claim 20 , wherein R 4a  is hydrogen, C 1 -C 6 -alkyl, optionally substituted C 3 -C 12 -cycloalkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, or M 3 -M 12 -heterocyclyl and R 4b  is hydrogen or C 1 -C 6 -alkyl; or wherein R 4a , R 4b  together are optionally substituted C 2 -C 6 -alkylene, wherein one —CH 2 — of C 2 -C 6 -alkylene may be replaced by an oxygen atom. 
     
     
         33 . The method of  claim 20 , wherein X 2  is >CR 12a R 12b , X 3  is a bond, and R 12a  is hydrogen or C 1 -C 6 -alkyl and R 12b  is hydrogen or C 1 -C 6 -alkyl. 
     
     
         34 . The method of  claim 20 , wherein the compound of formula (I) is 
       
         
           
           
               
               
           
         
       
       wherein R 16a R 16b , R 16c , R 16d , R 16e  independently are hydrogen, halogen, or halogenated C 1 -C 6 -alkyl. 
     
     
         35 . The method of  claim 20 , wherein m is 1. 
     
     
         36 . The method of  claim 20 , wherein
 A is a benzene ring;   R 1  is C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, or optionally substituted M 3 -M 12  heterocyclyl;   W is a bond;   A 1  is a bond;   Q is —S(O) 2 —;   Y is —NR 8 —;   n1 is 1 or 2;   n2 is 1 or 2;   R 6  is hydrogen, C 1 -C 6 -alkyl, or two radicals R 6  together with the carbon atom to which they are attached form a carbonyl group;   X 1  is ->N— or >CH—;   R 2  is hydrogen;   m is 1;   R 3  is hydrogen;   Y 1  is a bond;   R 4a , R 4b  
 together are optionally substituted C 2 -C 6 -alkylene; 
   X 2  is >CR 12a R 12b ;   X 3  is a bond;   R 5  is optionally substituted phenyl;   R 12a  is hydrogen;   R 12b  is hydrogen; and   R 12b  is hydrogen.   
     
     
         37 . The method of  claim 20 , wherein the compound of formula (I) is selected from the group consisting of:
 N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)-1-methyl-1H-imidazole-4-sulfonamide;   N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)-1-methyl-1H-pyrazole-4-sulfonamide;   N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)methanesulfonamide;   N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)ethanesulfonamide;   N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)propane-1-sulfonamide;   N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)-2,2-difluorobenzo[d][1,3]dioxole-5-sulfonamide;   N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)-3-methylazetidin-3-yl)-1-methyl-1H-imidazole-4-sulfonamide;   N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)-3-methylazetidin-3-yl)ethanesulfonamide;   N—((R)-1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin-3-yl)-1-methyl-1H-imidazole-4-sulfonamide;   N—((S)-1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin-3-yl)-1-methyl-1H-imidazole-4-sulfonamide;   N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)piperidin-4-yl)-1-methyl-1H-imidazole-4-sulfonamide;   N-((1R,3r)-3-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclobutyl)-1-methyl-1H-imidazole-4-sulfonamide;   N-((1S,3s)-3-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclobutyl)-1-methyl-1H-imidazole-4-sulfonamide;   N—((S)-1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-oxopyrrolidin-3-yl)propane-1-sulfonamide;   N-(1-((7S,8R)-8-benzyl-7-(3-azabicyclo[3.1.0]hexan-3-yl)-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)-1-methyl-1H-imidazole-4-sulfonamide;   N-(1-((7S,8R)-8-benzyl-7-(3-azabicyclo[3.1.0]hexan-3-yl)-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)-1-methyl-1H-1,2,3-triazole-4-sulfonamide;   N-(1-((7S,8R)-8-benzyl-7-(3-azabicyclo[3.1.0]hexan-3-yl)-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)propane-1-sulfonamide;   or a physiologically tolerated salt thereof.   
     
     
         38 . The method of  claim 20 , wherein the compound of formula (I) is N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)ethanesulfonamide, or a physiologically tolerated salt thereof. 
     
     
         39 . The method of  claim 20 , wherein the compound of formula (I) is N-(1-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)azetidin-3-yl)propane-1-sulfonamide, or a physiologically tolerated salt thereof. 
     
     
         40 . The method of  claim 20 , wherein the neurologic or psychiatric disorder is selected from the group consisting of attention deficit hyperactivity disorder, schizophrenia, psychotic disorder associated with schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition and substance-induced psychotic disorder, cognitive disorder, delirium, amnestic disorders or cognitive impairment including age related cognitive decline, anxiety disorder, substance-related disorder, obesity, bulimia nervosa, compulsive eating disorder, bipolar disorder, mood disorder, learning disorder, pervasive developmental disorder, movement disorder, medication-induced parkinsonism, Gilles de la Tourette's syndrome, epilepsy, muscular spasms, disorders associated with muscular spasticity or weakness, tremors; dyskinesias, urinary incontinence, neuronal damage including ocular damage, retinopathy or macular degeneration of the eye, tinnitus, hearing impairment and loss, brain edema, emesis, and sleep disorder 
     
     
         41 . The method of  claim 40 , wherein the cognitive disorder is selected from the group consisting of dementia associated with Alzheimer's disease, dementia associated with ischemia, multi-infarct dementia, dementia associated with trauma, dementia associated with vascular problems or stroke, dementia associated with HIV disease, dementia associated with Parkinson's disease, dementia associated with Huntington's disease, dementia associated with Pick's disease, dementia associated with Creutzfeldt-Jacob disease, dementia associated with perinatal hypoxia, and dementia associated with substance abuse. 
     
     
         42 . The method of  claim 40 , wherein the anxiety disorder is selected from the group consisting of acute stress disorder, agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, panic attack, panic disorder, post-traumatic stress disorder, separation anxiety disorder, social phobia, specific phobia, substance-induced anxiety disorder, and anxiety due to a general medical condition. 
     
     
         43 . The method of  claim 40 , wherein the substance-related disorder is selected from the group consisting of substance-induced delirium, persisting dementia, persisting amnestic disorder, psychotic disorder or anxiety disorder, tolerance, dependence or withdrawal from substances, wherein the substances are selected from the group consisting of alcohol, amphetamines, cannabis, cocaine, hallucinogens, inhalants, nicotine, opioids, phencyclidine, sedatives, hypnotics or anxiolytics. 
     
     
         44 . The method of  claim 40 , wherein the mood disorder is selected from the group consisting of depression, unipolar depression, seasonal depression and post-partum depression, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PDD), mood disorders due to a general medical condition, and substance-induced mood disorders. 
     
     
         45 . The method of  claim 40 , wherein the pervasive development disorder is selected from the group consisting of disorder including autistic disorder, attention deficit disorders including attention-deficit hyperactivity disorder (ADHD) and conduct disorder. 
     
     
         46 . The method of  claim 40 , wherein the movement disorder is akinesias or akinetic-rigid syndromes. 
     
     
         47 . The method of  claim 40 , wherein the sleep disorder is insomnia or narcolepsy. 
     
     
         48 . A method for treating a neurologic or psychiatric disorder or pain in a mammalian patient in need thereof which comprises administering to the patient a pharmaceutical composition comprising a carrier and an effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         A is a 5- or 6-membered ring; 
         R 1  is hydrogen, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 6 -alkyl, tri-(C 1 -C 4 -alkyl)-silyl-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylcarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkyloxycarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylaminocarbonylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylaminocarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylsulfonylamino-C 1 -C 4 -alkyl, (optionally substituted C 6 -C 12 -aryl-C 1 -C 6 -alkyl)amino-C 1 -C 4 -alkyl, optionally substituted C 6 -C 12 -aryl-C 1 -C 4 -alkyl, optionally substituted M 3 -M 12 -heterocyclyl-C 1 -C 4 -alkyl, C 3 -C 12 -cycloalkyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, halogenated C 1 -C 6 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, aminocarbonyl, C 1 -C 6 -alkylaminocarbonyl, (halogenated C 1 -C 4 -alkyl)aminocarbonyl, C 6 -C 12 -arylaminocarbonyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkoxy, halogenated C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, amino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylamino-C 1 -C 4 -alkoxy, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylcarbonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -arylcarbonylamino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkoxycarbonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -aryl-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylsulfonylamino-C 1 -C 4 -alkoxy, (halogenated C 1 -C 6 -alkyl)sulfonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -arylsulfonylamino-C 1 -C 4 -alkoxy, (C 6 -C 12 -aryl-C 1 -C 6 -alkyl)sulfonylamino-C 1 -C 4 -alkoxy, M 3 -M 12 -heterocyclylsulfonylamino-C 1 -C 4 -alkoxy, M 3 -M 12 -heterocyclyl-C 1 -C 4 -alkoxy, C 6 -C 12 -aryloxy, M 3 -M 12 -heterocyclyloxy, C 1 -C 6 -alkylthio, halogenated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylamino, (halogenated C 1 -C 6 -alkyl)amino, di-C 1 -C 6 -alkylamino, di-(halogenated C 1 -C 6 -alkyl)amino, C 1 -C 6 -alkylcarbonylamino, (halogenated C 1 -C 6 -alkyl)carbonylamino, C 6 -C 12 -arylcarbonylamino, C 1 -C 6 -alkylsulfonylamino, (halogenated C 1 -C 6 -alkyl)sulfonylamino, C 6 -C 12 -arylsulfonylamino or optionally substituted M 3 -M 12 -heterocyclyl; 
         W is —NR 7 — or a bond; 
         A 1  is optionally substituted C 1 -C 4 -alkylene or a bond; 
         Q is —S(O) 2 — or —C(O)—; 
         Y is —NR 8 — or a bond; 
         n1 is 0, 1, 2, or 3; 
         n2 is 0, 1, 2, or 3; 
         X 1  is >N— or >CH—; 
         R 6  is hydrogen, halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, —CN, hydroxy, C 1 -C 6 -alkoxy or halogenated C 1 -C 6 -alkoxy, or two radicals R 6  together with the carbon atom to which they are attached form a carbonyl group; 
         R 2  is hydrogen, halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 4 -alkyl, —CN, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkoxy, halogenated C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkenyloxy, C 6 -C 12 -aryl-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylcarbonyloxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, aminosulfonyl, amino, C 1 -C 6 -alkylamino, C 2 -C 6 -alkenylamino, nitro or optionally substituted M 3 -M 12 -heterocyclyl, or two radicals R 2  together with the ring atoms of A to which they are bound form a 5- or 6 membered ring; 
         m is 0 or 1; 
         R 3  is hydrogen, halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy, or two radicals R 3  together with the carbon atom to which they are attached form a carbonyl group; 
         Y 1  is a bond or optionally substituted C 1 -C 4 -alkylene; 
         R 4a  is hydrogen, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, —CH 2 CN, C 6 -C 12 -aryl-C 1 -C 4 -alkyl, optionally substituted C 3 -C 12 -cycloalkyl, —CHO, C 1 -C 4 -alkylcarbonyl, (halogenated C 1 -C 4 -alkyl)carbonyl, C 6 -C 12 -arylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, C 1 -C 6 -alkylaminocarbonyl, C 2 -C 6 -alkenyl, —C(═NH)NH 2 , —C(═NH)NHCN, C 1 -C 6 -alkylsulfonyl, C 6 -C 12 -arylsulfonyl, amino, —NO or optionally substituted M 3 -M 12 -heterocyclyl; or 
         R 4a  is optionally substituted C 1 -C 4 -alkylene that is bound to a carbon atom in Y 1 ; 
         R 4b  is hydrogen, C 1 -C 6 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, —CH 2 CN, —CHO, C 1 -C 4 -alkylcarbonyl, (halogenated C 1 -C 4 -alkyl)carbonyl, C 6 -C 12 -arylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, C 1 -C 6 -alkylaminocarbonyl, C 2 -C 6 -alkenyl, —C(═NH)NH 2 , —C(═NH)NHCN, C 1 -C 6 -alkylsulfonyl, C 6 -C 12 -arylsulfonyl, amino, —NO or M 3 -M 12 -heterocyclyl; or 
         R 4a , R 4b  
 together are optionally substituted C 2 -C 6 -alkylene, wherein one —CH 2 — of C 2 -C 6 -alkylene may be replaced by an oxygen atom or —NR 10 ; 
 
         X 2  is —O—, —NR 11a —, —S—, >CR 12a R 12b  or a bond; 
         X 3  is —O—, —NR 11b —, —S—, >CR 13a R 13b  or a bond; 
         R 5  is optionally substituted C 6 -C 12 -aryl, optionally substituted C 3 -C 12 -cycloalkyl or optionally substituted M 3 -M 12 -heterocyclyl; 
         R 7  is hydrogen or C 1 -C 6 -alkyl; 
         R 8  is hydrogen, C 1 -C 6 -alkyl, C 3 -C 1 -cycloalkyl, amino-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl-C 1 -C 4 -alkyl or M 3 -M 12 -heterocyclyl; or 
         R 8 , R 1  
 together are C 1 -C 4 -alkylene; 
 
         R 10  is hydrogen or C 1 -C 6 -alkyl; 
         R 11a  is hydrogen or C 1 -C 6 -alkyl; 
         R 11b  is hydrogen or C 1 -C 6 -alkyl; 
         R 12a  is hydrogen, optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, M 3 -M 12 -heterocyclyl-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl or hydroxy; 
         R 12b  is hydrogen or C 1 -C 6 -alkyl, or 
         R 12a , R 12b  
 together with the carbon atom to which they are attached form a carbonyl or are optionally substituted C 2 -C 4 -alkylene, wherein one —CH 2 — of C 2 -C 4 -alkylene may be replaced by an oxygen atom or —NR 14 —; 
 
         R 13a  is hydrogen, optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, M 3 -M 12 -heterocyclyl-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl or hydroxy; 
         R 13b  is hydrogen or C 1 -C 6 -alkyl, or 
         R 13a , R 13b  
 together with the carbon atom to which they are attached form a carbonyl or are optionally substituted C 1 -C 4 -alkylene, wherein one —CH 2 — of C 1 -C 4 -alkylene may be replaced by an oxygen atom or —NR 15 —; 
 
         R 14  is hydrogen or C 1 -C 6 -alkyl; and 
         R 5  is hydrogen or C 1 -C 6 -alkyl, 
         or a physiologically tolerated salt thereof.