Compounds having 5-ht6 receptor affinity

Abstract

The present disclosure provides compounds having affinity for the 5HT6 receptor which are of the formula (I): wherein R 1 -R 3 A, B, D, E, G, Q, and x are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

1 . A compound of formula I: 
     
       
         
         
             
             
         
       
     
     wherein
 A, B, D, E and G, are each CH, CR 4  or N wherein at least one of A, B, D, E, or G is N; 
 - - - - - represents a single bond or a double bond; 
 Q is C when - - - - is a double bond, and Q is CH or N when - - - - - is a single bond; 
 x is 0, 1, 2, 3, or 4; 
 R 1  is SO 2 Ar, wherein 
 Ar is selected from formulas (a)-(r): 
 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Wherein
 J is CR 7  or N; 
 in formula (o), one K is N and the other is CH; 
 J is CR 7  or N; 
 K is, in each instance independently, CH or N; 
 W is O, S, or is absent; 
 X is, in each instance independently, O or NR 7 ; 
 Y is O, NR 7  or S; 
 Z is S or NR 7 ; 
 a is 1, 2, 3, 4 or 5; 
 b, l, m and v are independently 0, 1, 2, 3 or 4; 
 c, f, h, n, o, q, s, and u are independently 0, 1, 2 or 3; 
 d, and e are independently 1, 2 or 3; 
 g, i, j, and p are independently 0, 1 or 2; 
 k and t are 0 or 1; 
 R 2  is H or alkyl having 1 to 8 carbon atoms, cycloalkyl having 3 to 12 carbon atoms, or cycloalkylalkyl having 4 to 12 carbon atoms, each of which is branched or unbranched and each of which is unsubstituted or substituted one or more times with halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or any combination thereof; 
 R 3  is H or alkyl having 1 to 8 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or any combination thereof; 
 R 4  is halogen, nitro, alkyl having 1 to 8 carbon atoms, cycloalkyl having 3 to 12 carbon atoms, or cycloalkylalkyl having 4 to 12 carbon atoms, each of which is branched or unbranched and wherein the alkyl, cycloalkyl or cycloalkylalkyl is unsubstituted or substituted one or more times with halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or any combination thereof,
 an alkoxy having 1 to 8 carbon atoms, or 
 a heterocyclic group, which is saturated, partially saturated or unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is an N, O or S atom, which is unsubstituted or substituted one or more times by halogen, hydroxy, C 5-7 -aryl, C 1-4 -alkoxy, cyano, halogenated alkyl, nitro, or any combination thereof, 
 
 R 5  is amino, C 1-4 -alkylamino, C 1-4 -dialkylamino, NR 6 C(O)R 8 ,
 a heterocyclic group, which is saturated, partially saturated or unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is an N, O or S atom, which is unsubstituted or substituted one or more times by halogen, hydroxy, C 5-7 -aryl, C 1-4 -alkyl, C 1-4 -alkoxy, cyano, halogenated C 1-4 -alkyl, or —O—Ar′, wherein Ar′ is an C 5-7 -aryl; 
 
 R 6  is H or alkyl having 1 to 8 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times with halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or any combination thereof; 
 R 7  is, in each instance, independently H, halogen C(O)R 8 , CO 2 R 8 , NR 6 COR 8 , an alkyl having 1 to 12 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen, hydroxy, cyano, C 1-4 -alkoxy, oxo or any combination thereof, and wherein optionally one or more —CH 2 CH 2 — groups is replaced in each instance by —CH═CH— or —C—═C—,
 alkoxy having 1 to 8 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen, 
 cycloalkyl having 3 to 10 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, oxo, cyano, C 1-4 -alkyl, C 1-4 -alkoxy, or any combination thereof, 
 cycloalkylalkyl having 4 to 16 carbon atoms, which is unsubstituted or substituted in the cycloalkyl portion and/or the alkyl portion one or more times by halogen, oxo, cyano, hydroxy, C 1-4 -alkyl, C 1-4 -alkoxy or any combination thereof, 
 aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, CF 3 , OCF 3 , C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, cyano, or any combination thereof, 
 arylalkyl in which the aryl portion has 6 to 14 carbon atoms and the alkyl portion, which is branched or unbranched, has 1 to 5 carbon atoms, wherein the arylalkyl radical is unsubstituted, substituted in the aryl portion one or more times by halogen, CF 3 , OCF 3 , C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, cyano, methylenedioxy, ethylenedioxy, or any combination thereof, and/or substituted in the alkyl portion one or more times by halogen, oxo, hydroxy, cyano, or any combination thereof, and wherein in the alkyl portion one or more —CH 2 CH 2 — groups are each optionally replaced by —CH═CH— or —C/C— and one or more —CH 2 -groups are each optionally replaced by —O— or —NH—, 
 a heterocyclic group, which is saturated, partially saturated or unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is an N, O or S atom, which is unsubstituted or substituted one or more times by halogen, hydroxy, C 5-7 -aryl, C 1-4 -alkyl, C 1-4 -alkoxy, cyano, trifluoromethyl, nitro, oxo, or any combination thereof, or 
 a heterocycle-alkyl group, wherein the heterocyclic portion is saturated, partially saturated or unsaturated, and has 5 to 10 ring atoms in which at least 1 ring atom is an N, O or S atom, and the alkyl portion is branched or unbranched and has 1 to 5 carbon atoms, the heterocycle-alkyl group is unsubstituted, substituted one or more times in the heterocyclic portion by halogen, OCF 3 , hydroxy, C 5-7 -aryl, C 1-4 -alkyl, C 1-4 -alkoxy, cyano, trifluoromethyl, nitro, oxo, or any combination thereof, and/or substituted in the alkyl portion one or more times by halogen, oxo, hydroxy, cyano, or any combination thereof, and wherein in the alkyl portion one or more —CH 2 CH 2 — groups are each optionally replaced by —CH═CH— or —C/C—, and one or more —CH 2 — groups are each optionally replaced by —O— or —NH—; 
 
 R 8  is in each instance, independently, H or alkyl having 1 to 8, carbon atoms carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen; 
 
     or a pharmaceutically acceptable salt thereof; 
     with the following provisos:
 (i) when Ar is represented by formula (j) and G is CH or CR 4 , then at least one of A, B, D, or E represents CR 4  in which R 4  is other than H, halogen, alkyl, halogenated alkyl, or alkoxy; or when Ar is represented by formula (j) and G is N, then at least one of A, B, D, or E represents CR 4  in which R 4  is other than H, halogen, alkyl, halogenated alkyl, alkoxy, —OH, —NH 2 , or NO 2 ; 
 (ii) when one of A, B, D, or E represents N and the rest are CH, G is CH, and Ar is represented by one of formulas (d)-(i), then at least one R 7  substituent on said formula (d)-(i) is other than H, halogen, hydroxyl, alkyl, alkoxy, halogenated alkyl, halogenated alkoxy; and 
 (iii) when G is N and A, B, and D are CH or CR 4 , then:
 (1) R 2  is alkyl having 1 to 8 carbon atoms, 
 (2) Q is N, 
 (3) Ar is selected from formulas (d)-(g), or 
 (4) a combination of at least two of (1)-(3). 
 
 
   
   
       2 . The compound of  claim 1 , wherein R 2  is H. 
   
   
       3 . The compound of  claim 1 , wherein - - - - - represents a single bond and Q is CH or N. 
   
   
       4 . The compound of  claim 1 , wherein Ar is (a). 
   
   
       5 . The compound of  claim 1 , wherein Ar is (c). 
   
   
       6 . (canceled) 
   
   
       7 . The compound of  claim 1 , wherein Ar is (k). 
   
   
       8 . The compound of  claim 1 , wherein Ar is (n). 
   
   
       9 . The compound of  claim 8 , wherein Ar is 
     
       
         
         
             
             
         
       
       wherein W is O or is absent and X is, in each instance independently, O, NH, or N—CH 3 . 
     
   
   
       10 . (canceled) 
   
   
       11 . The compound of  claim 1 , wherein
 Q is N,   A, B, and D are CH,   E is CH or NH,   R 2  is H or CH 3 ,   R 3  is H, and   R 1  is SO 2 Ar wherein Ar is a heterocycle selected from formulas (a), (c) and (n).   
   
   
       12 - 35 . (canceled) 
   
   
       36 . The compound of  claim 1 , wherein
 A, D, and G are CH,   E is N,   B is CR 4  wherein R 4  is H, halogen or halogenated alkyl, and   R 1  is SO 2 Ar wherein Ar is phenyl substituted at least once by amino, dialkylamino, NR 6 COR 8 , N(CH 3 )COCH 3 ), or substituted or unsubstituted heterocyclic group,   pyridinyl substituted at least once by substituted or unsubstituted heterocyclic group,   unsubstituted or substituted moiety selected from the group consisting of dihydrobenzofuranyl, dihydrobenzodioxepinyl, dihydroindoly, and tetrahydroisoquinolinyl, or   thiazolyl substituted at least once by aryl.   
   
   
       37 . The compound of  claim 1 , wherein
 A, D, and G are CH,   E is N,   B is CR 4  wherein R 4  is H, halogen or halogenated alkyl, and   R 1  is SO 2 Ar wherein Ar is phenyl substituted at least once by amino, dialkylamino, NR 6 COR 8 , N(CH 3 )COCH 3 ), or substituted or unsubstituted heterocyclic group,
 pyridinyl substituted at least once by substituted or unsubstituted heterocyclic group, 
 unsubstituted or substituted dihydrobenzofuranyl, 
 unsubstituted or substituted dihydrobenzodioxepinyl, 
 thiazolyl substituted at least once by aryl, 
 unsubstituted dihydroindolyl or dihydroindolyl substituted by one or more acetyl and/or alkyl groups, or 
 unsubstituted tetrahydroisoquinolinyl or tetrahydroisoquinolinyl substituted by one or more alkyl groups. 
   
   
   
       38 . The compound of  claim 1 , wherein
 A, B, D, and G are CH,   E is N, and   R 1  is SO 2 Ar wherein Ar is 4-aminophenyl, 4-dimethylaminophenyl, 3-dimethylaminophenyl, p-C 6 H 4 (NHCOCH 3 ), p-C 6 H 4 (N(CH 3 )COCH 3 ) ,  3-(2-methylpyrimidin-4-yl)phenyl, 4-morpholin-4-ylphenyl, 4-pyrrolidin-1-ylphenyl, 3-pyrrolidin-1-ylphenyl, 4-morpholin-4-yl-pyridin-3-yl, 2,3-dihydrobenzofuran-5-yl, 3,4-dihydro-2H-1,5-benzodioxepin-7-yl, 4-methyl-2-phenyl-1,3-thiazol-5yl, 2,3,dihydro-1-H-indol-5-yl, 1-acetyl-2,3,dihydro-1-H-indol-5-yl, 1-methyl-2,3,dihydro-1-H-indol-5-yl, 1-ethyl-2,3,dihydro-1-H-indol-5-yl), 1,2,3,4-tetrahydroisoquinolin-7-yl, 1-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl, or 1-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl.   
   
   
       39 - 40 . (canceled) 
   
   
       41 . The compound of  claim 1 , wherein
 A, D and G are CH,   B is CR 4  wherein R 4  is H, halogen, halogenated alkyl, nitro, pyridine, dimethylpyrrole, tetrahydropyrrole, tetrahydropyridine, or tetrahydrooxazine,   E is N,   R 2  is CH 3 ,   R 3  is H,   - - - is a double bond and Q is C.   
   
   
       42 - 44 . (canceled) 
   
   
       45 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 N-(4-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}phenyl)acetamide,   1 (2,3-dihydro-1-benzofuran-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1 (3,4-dihydro-2H-1,5-benzodioxepin-7-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-[(4-methyl-2-phenyl-1,3-thiazol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   Methyl 5-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-2-furoate,   1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1 (1,3-benzodioxol-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-{[3-(2-methylpyrimidin-4-yl)phenyl]sulfonyl}-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine, and   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       46 . (canceled) 
   
   
       47 . The compound of  claim 1 , wherein the salt is the hydrochloride salt. 
   
   
       48 . (canceled) 
   
   
       49 . The compound of  claim 1 , wherein the salt is the hydroformate salt 
   
   
       50 . The compound of  claim 73  wherein the compound is 7-{[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one or a pharmaceutically acceptable salt thereof. 
   
   
       51 - 52 . (canceled) 
   
   
       53 . The method of  claim 58 , further comprising treating a central nervous system disorder (CNS), a memory/cognitive impairment, a gastrointestinal (GI) disorder, or a polyglutamine-repeat disease by administering a pharmacologically effective amount of a compound according to  claim 1  to a patient in need thereof. 
   
   
       54 . The method of  claim 53 , wherein the CNS disorder is Alzheimer's disease, Parkinson's disease, Huntington's disease, anxiety, depression, manic depression, epilepsy, obsessive compulsive disorders, migraine, sleep disorders, feeding disorders such as anorexia and bulimia, panic attacks, attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), withdrawal from drug abuse, psychoses, or disorders associated with spinal trauma and/or head injury. 
   
   
       55 . The method of  claim 53 , wherein the memory/cognitive impairment is associated with Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease Pick's disease, Creutzfeld Jakob disease, HIV, cardiovascular disease, head trauma or age-related cognitive decline. 
   
   
       56 . (canceled) 
   
   
       57 . The method of  claim 53 , wherein the compound of  claim 1  is administered in a pharmaceutically acceptable carrier. 
   
   
       58 . A method of modulating 5-HT6 receptor activity comprising administering a pharmacologically effective amount of a compound according to  claim 1  to a patient in need thereof. 
   
   
       59 . (canceled) 
   
   
       60 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       61 - 62 . (canceled) 
   
   
       63 . A compound of formula I: 
     
       
         
         
             
             
         
       
     
     wherein
 A, B, D, E and G, are each CH, CR 4 , or N, wherein at least one of A, B, D, E and G is N, 
 at least one of A, B, D, or E is CR 4 , where R 4  is a substituted or unsubstituted heterocyclic group; 
 - - - - - represents a single bond or a double bond; 
 Q is C when - - - - is a double bond, and Q is CH or N when - - - - - is a single bond; 
 x is 0, 1, 2, 3, or 4; 
 R 1  is SO 2 Ar, wherein 
 Ar is unsubstituted phenyl or unsubstituted pyridinyl; 
 R 2  is H or alkyl having 1 to 8 carbon atoms, cycloalkyl having 3 to 12 carbon atoms, or cycloalkylalkyl having 4 to 12 carbon atoms, each of which is branched or unbranched and each of which is unsubstituted or substituted one or more times with halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or any combination thereof; 
 R 3  is H or alkyl having 1 to 8 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or any combination thereof; and 
 R 4  is halogen, nitro, alkyl having 1 to 8 carbon atoms, cycloalkyl having 3 to 12 carbon atoms, or cycloalkylalkyl having 4 to 12 carbon atoms, each of which is branched or unbranched and which is unsubstituted or substituted one or more times with halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or any combination thereof,
 an alkoxy having 1 to 8 carbon atoms, or 
 a heterocyclic group, which is saturated, partially saturated or unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is an N, O or S atom, which is unsubstituted or substituted one or more times by halogen, hydroxy, C 5-7 -aryl, C 1-4 -alkyl, C 1-4 -alkoxy, cyano, halogenated alkyl, nitro, or any combination thereof, 
 
 
     or a pharmaceutically acceptable salt thereof. 
   
   
       64 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1-[(6-morpholin-4-ylpyridin-3-yl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine,   1-(2,3-dihydro-1H-indol-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   4-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}aniline, 3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1-[(4-morpholin-4-ylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine,   N,N-dimethyl-4-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}aniline,   N,N-dimethyl-3-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}aniline,   1-[(1-methyl-2,3-dihydro-1H-indol-6-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-[(1-ethyl-2,3-dihydro-1H-indol-6-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   N-methyl-N-(4-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}phenyl)acetamide, and   7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-1,2,3,4-tetrahydroquinoline,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       65 . The compound of  claim 1 , wherein the compound is selected from the group consisting of
 methyl-7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-1,2,3,4-tetrahydroquinoline,   methyl-6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-1,2,3,4-tetrahydroquinoline,   3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1-[(4-pyrrolidin-1-ylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine,   3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1-[(3-pyrrolidin-1-ylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine,   1-[(1-methyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-(2,2-dimethylpropanoyl)-5-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3 b]pyridin-1-yl]sulfonyl}-1H-indazole   6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}dihydroquinolin-2(1H)-one,   methyl-6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-3,4-dihydroquinolin-2(1H)-one, and   1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-3-(1-methylpiperidin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       66 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-{[6-(3-methoxypyrrolidin-1-yl)pyridin-3-yl]sulfonyl}-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   1-[(1-acetyl-2,3-dihydro-1H-indol-6-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   4-methyl-7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-3,4->dihydro-2H-1,4-benzoxazine,   1-(4-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}phenyl)pyrrolidin-2-one,   methyl-6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-1,3-benzoxazol-2(3H)-one,   1-[(1-methyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine, and   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       67 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methylpiperidin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-3-piperidin-4-yl-1H-pyrrolo[2,3-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-piperidin-4-yl-1H-pyrrolo[2,3-b]pyridine,   1-{[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl}-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-(3-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}phenyl)pyrrolidin-2-one,   1-[(5-bromo-2,3-dihydro-1-benzofuran-7-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine, and   6-ethyl-1-[(1-methyl-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       68 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 6-ethyl-1-[(1-methyl-1H-indol-6-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   6-ethyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1-[(3-pyrrolidin-1-ylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine,   6-ethyl-1-{[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl}-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-(3-{[6-ethyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl]sulfonyl}phenyl)pyrrolidin-2-one,   1-[(5-bromo-2,3-dihydro-1-benzofuran-7-yl)sulfonyl]-6-ethyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-6-ethyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-6-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-piperazin-1-yl-1H-pyrrolo[2,3-b]pyridine, and   1-{[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl}-3-piperazin-1-yl-1H-pyrrolo[2,3-b]pyridine,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       69 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   4-methyl-7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-3,4-dihydro-2H-1,4-benzoxazine,   1-[(1-methyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   1-(4-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}phenyl)pyrrolidin-2-one,   3-methyl-6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-1,3-benzoxazol-2(3H)-one,   5-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyri din-1-yl]sulfonyl}-1,3-dihydro-2H-benzimidazol-2-one,   7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one, and   1-(3,4-dihydro-2H-1,5-benzodioxepin-7-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       70 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 4-methyl-6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-3,4-dihydro-2H-1,4-benzoxazine,   4-methyl-7-{[3-(1-methylpiperidin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-3,4-dihydro-2H-1,4-benzoxazine,   4-methyl-7-{[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-3,4-dihydro-2H-1,4-benzoxazine,   4-methyl-7-[(3-piperidin-4-yl-1H-pyrrolo[3-2-b]pyridin-1-yl)sulfonyl]-3,4-dihydro-2H-1,4-benzoxazine,   1-{[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl}-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   1-(3-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyri din-1-yl]sulfonyl}phenyl)pyrrolidin-2-one,   1-[(5-bromo-2,3-dihydro-1-benzofuran-7-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   4-Methyl-7-(3-piperidin-4-yl-pyrrolo[3-2-b]pyridine-1-sulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine,   1-(3-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}phenyl)pyrrolidin-3-ol, and   1-[(6-morpholin-4-ylpyridin-3-yl)sulfonyl]-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       71 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 1-{[6-(3-methoxypyrrolidin-1-yl)pyridin-3-yl]sulfonyl}-3-(1,2,3,6-tetrahydropyridin-4-yl)-1,1-pyrrolo[3-2-b]pyridine,   1-[(5-methoxypyridin-3-yl)sulfonyl]-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   1-{[5-(3-methoxypyrrolidin-1-yl)pyridin-3-yl]sulfonyl}-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-13]pyridine,   7-{[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   7-{[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-3,4-dihydroquinolin-2(1H)-one,   4-methyl-6-{[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-3,4-dihydro-2H-1,4-benzoxazine,   6-{[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1-[(6-phenoxypyridin-3-yl)sulfonyl]-1H-pyrrolo[3-2-b]pyridine, and   2-methyl-8-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[3-2-b]pyridin-1-yl]sulfonyl}-1,2,3,4-tetrahydroisoquinoline,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       72 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 1-[(1,2-dimethyl-1H-imidazol-4-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   1-[(1,2-dimethyl-1H-imidazol-4-yl)sulfonyl]-5-fluoro-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   1-[(1,2-dimethyl-1H-imidazol-4-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5-(trifluoromethyl)-1H-indazole,   7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   1-[(1-methyl-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   4-methyl-7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-1-yl]sulfonyl}-3,4-dihydro-2H-1,4-benzoxazine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   4-acetyl-6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-1-yl]sulfonyl}-3,4-dihydro-2H-1,4-benzoxazine,   5-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-1-yl]sulfonyl}-1,2-benzisoxazole,   1-(1-benzothien-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   1-(1-benzofuran-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   6-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazol-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one, and   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-5-fluoro-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       73 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 5-fluoro-1-[(1-methyl-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   5-fluoro-1-[(1-methyl-1H-indol-6-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indazole,   1-{[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl}-3-(4-methylpiperazin-1-yl)-1H-indazole,   1-{[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl}-3-piperazin-1-yl-1H-indazole,   7-[(3-piperazin-1-yl-1H-indazol-1-yl)sulfonyl]-2H-1,4-benzoxazin-3(4H)-one,   7-{[3-(4-methylpiperazin-1-yl)-1H-indazol-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(4-methylpiperazin-1-yl)-1H-indazole,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-piperazin-1-yl-1H-indazole,   3-piperazin-1-yl-1-(pyridin-3-ylsulfonyl)-1H-indazole,   4-methyl-7-{[3-(4-methylpiperazin-1-yl)-1H-indazol-1-yl]sulfonyl}-3,4-dihydro-2H-1,4-benzoxazine,   4-methyl-7-[(3-piperazin-1-yl-1H-indazol-1-yl)sulfonyl]-3,4-dihydro-2H-1,4-benzoxazine, and   7-[(3-piperazin-1-yl-1H-indazol-1-yl)sulfonyl]-2H-1,4-benzoxazin-3(4H)-one,   
     or a pharmaceutically acceptable salt thereof. 
   
   
       74 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 1-(1-benzofuran-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[4,3-b]pyridine,   1-(1-benzothien-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[4,3-b]pyridine,   1-(1-benzofuran-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine,   1-(1-benzothien-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine,   1-{[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl}-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[4,3-b]pyridine,   1-{[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl}-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine,   7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[4,3-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   7-{[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl]sulfonyl}-2H-1,4-benzoxazin-3(4H)-one,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine,   1-[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl]-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[4,3-b]pyridine,   1-(1,2-benzisoxazol-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[4,3-b]pyridine, and   1-(1,2-benzisoxazol-5-ylsulfonyl)-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridine,   
     or a pharmaceutically acceptable salt thereof.