Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof

Abstract

The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nAChR), activation of nAChRs, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (indazoles and benzothiazoles), which act as ligands for the α7 nAChR subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein
 x is O or S; 
 R 1  is H, F, Cl, Br, I, OH, CN, nitro, NH 2 , alkyl having 1 to 4 carbon atoms, fluorinated alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, alkoxy having 1 to 4 carbon atoms, cycloalkoxy having 3 to 7 carbon atoms, cycloalkylalkoxy having 4 to 7 carbon atoms, alkylthio having 1 to 4 carbon atoms, fluorinated alkoxy having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, hydroxyalkoxy having 2 to 4 carbon atoms, monoalkylamino having 1 to 4 carbon atoms, dialkylamino wherein each alkyl group independently has 1 to 4 carbon atoms, Ar or Het; 
 R 2  is H, alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, or cycloalkylalkyl having 4 to 7 carbon atoms; 
 Ar is an aryl group containing 6 to 10 carbon atoms which is unsubstituted or substituted one or more times by alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, halogen, dialkylamino wherein the alkyl portions each have 1 to 8 carbon atoms, amino, cyano, hydroxyl, nitro, halogenated alkyl having 1 to 8 carbon atoms, halogenated alkoxy having 1 to 8 carbon atoms, hydroxyalkyl having 1 to 8 carbon atoms, hydroxyalkoxy having 2 to 8 carbon atoms, alkenyloxy having 3 to 8 carbon atoms, alkylthio having 1 to 8 carbon atoms, alkylsulphinyl having 1 to 8 carbon atoms, alkylsulphonyl having 1 to 8 carbon atoms, monoalkylamino having 1 to 8 carbon atoms, cycloalkylamino wherein the cycloalkyl group has 3 to 7 carbon atoms and is optionally substituted by C 1-4 -alkyl, C 1- alkoxy, hydroxylamino, monoalkylamino having 1 to 4 carbon atoms, and/or dialklyamino in which each alkyl group has 1 to 4 carbon atoms, aryloxy wherein the aryl portion contains 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl C 1-4 -hydroxyalkoxy, carboxy, cyano, C 1-4 -alkoxy-carbonyl C 1-4 -alkylthio, C 1-4 -alkylsulphinyl C 1-4 alkylsulphonyl, phenoxy, or acetoxy, arylthio wherein the aryl portion contains 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, C 1-4 -alkoxy-carbonyl C 1-4 -alkylthio, C 1-4 -alkylsulphinyl C 1-4 -alkylsulphonyl, phenoxy, or acetoxy, cycloalkyloxy wherein the cycloalkyl group has 3 to 7 carbon atoms and is optionally substituted by C 1-4 -alkyl, C 1-4 -alkoxy, hydroxyl, amino, monoalkylamino having 1 to 4 carbon atoms, and/or dialklyamino in which each alkyl group has 1 to 4 carbon atoms, sulfo, sulfonylamino, or combinations thereof; and 
 Het is a heterocyclic group, which is fully saturated, partially saturated or fully unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, aryl having 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy carboxy, cyano, C 1-4 -alkoxy-carbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or acetoxy, alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, cyano, trifluoromethyl, nitro, oxo, amino, monoalkylamino having 1 to 8 carbon atoms, dialkylamino wherein each alkyl group has 1 to 8 carbon atoms, 
 or combinations thereof; or 
 a pharmaceutically acceptable salt thereof, 
 wherein if the compound exhibits chirality it can be in the form of a mixture of enantiomers such as a racemate or a mixture of diastereomers, or can be in the form of a single enantiomer or a single diastereomer 
 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
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         5 . (canceled) 
     
     
         6 . A compound according to Formula I′: 
       
         
           
           
               
               
           
         
       
       wherein
 A is an indazolyl according to subformula (a), 
 R 1  is H, F, Cl, Br, I, OH, CN, nitro, NH 2 , alkyl having 1 to 4 carbon atoms, fluorinated alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, alkoxy having 1 to 4 carbon atoms, cycloalkoxy having 3 to 7 carbon atoms, alkylthio having 1 to 4 carbon atoms, fluorinated alkoxy having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, hydroxyalkoxy having 2 to 4 carbon atoms, monoalkylamino having 1 to 4 carbon atoms, dialkylamino wherein each alkyl group independently has 1 to 4 carbon atoms, Ar or Het; 
 R 2  is H, alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, or cycloalkylalkyl having 4 to 7 carbon atoms; 
 Ar is an aryl group containing 6 to 10 carbon atoms which is unsubstituted or substituted one or more times by alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, halogen, dialkylamino wherein the alkyl portions each have 1 to 8 carbon atoms, amino, cyano, hydroxyl, nitro, halogenated alkyl having 1 to 8 carbon atoms, halogenated alkoxy having 1 to 8 carbon atoms, hydroxyalkyl having 1 to 8 carbon atoms, hydroxyalkoxy having 2 to 8 carbon atoms, alkenyloxy having 3 to 8 carbon atoms, alkylthio having 1 to 8 carbon atoms, alkylsulphinyl having 1 to 8 carbon atoms, alkylsulphonyl having 1 to 8 carbon atoms, monoalkylamino having 1 to 8 carbon atoms, cycloalkylamino wherein the cycloalkyl group has 3 to 7 carbon C atoms and is optionally substituted by C 1-4 -alkyl C 1-4 -alkoxy, hydroxyl, amino, monoalkylamino having 1 to 4 carbon atoms, and/or dialklyamino in which each alkyl group has 1 to 4 carbon atoms, aryloxy wherein the aryl portion contains 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, C 1-4 -alkoxy-carbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or acetoxy, arylthio wherein the aryl portion contains 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C-hydroxyalkoxy, carboxy, cyano, C 1-4 -alkoxy-carbonyl, C 1-4 -alkylthio C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or acetoxy, cycloalkyloxy wherein the cycloalkyl group has 3 to 7 carbon atoms and is optionally substituted by C 1-4 -alkyl, C 1-4 -alkoxy, hydroxyl, amino, monoalkylamino having 1 to 4 carbon atoms, and/or dialklyamino in which each alkyl group has 1 to 4 carbon atoms, sulfo, sulfonylamino, or combinations thereof; and 
 Het is a heterocyclic group, which is fully saturated, partially saturated or fully unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, aryl having 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl C 1-4 -hydroxyalkoxy, carboxy, cyano, C 1-4 -alkoxy-carbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl C 1- -alkylsulphonyl, phenoxy, or acetoxy, alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, cyano, trifluoromethyl, nitro, oxo, amino, monoalkylamino having 1 to 8 carbon atoms, dialkylamino wherein each alkyl group has 1 to 8 carbon atoms, or combinations thereof; or 
 a pharmaceutically acceptable salt thereof. 
 wherein if the compound exhibits chirality it can be in the form of a mixture of enantiomers such as a racemate or a mixture of diastereomers, or can be in the form of a single enantiomer or a single diastereomer, and 
 wherein the indazolyl group of subformula (a) is attached to the remainder of the compound via its 3 position. 
 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
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         12 . (canceled) 
     
     
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         14 . (canceled) 
     
     
         15 . A method according to  claim 1 , wherein R 2  is H or methyl. 
     
     
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         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . A compound according to  claim 6 , wherein R 2  is H or methyl. 
     
     
         38 . A compound according to  claim 1 , wherein said compound is in the form of a hydrochloride or hydroformate salt. 
     
     
         39 . A compound according to  claim 6 , wherein said compound is in the form of a hydrochloride or hydroformate salt. 
     
     
         40 . A compound according to  claim 1 , wherein Ar is substituted or unsubstituted phenyl or naphthyl, and Het is substituted or unsubstituted tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, isoxazolinyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl, indolyl, quinolinyl, isoquinolinyl, or naphthyridinyl. 
     
     
         41 . A compound according to  claim 6 , wherein Ar is substituted or unsubstituted phenyl or naphthyl, and Het is substituted or unsubstituted tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, isoxazolinyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl, indolyl, quinolinyl, isoquinolinyl, or naphthyridinyl. 
     
     
         42 . A compound according to  claim 1 , wherein:
 Ar is an aryl group containing 6 to 10 carbon atoms which is unsubstituted or substituted one or more times by alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, halogen, dialkylamino wherein the alkyl portions each have 1 to 8 carbon atoms, amino, cyano, hydroxyl, nitro, halogenated alkyl having 1 to 8 carbon atoms, halogenated alkoxy having 1 to 8 carbon atoms, hydroxyalkyl having 1 to 8 carbon atoms, hydroxyalkoxy having 2 to 8 carbon atoms, alkenyloxy having 3 to 8 carbon atoms, alkylthio having 1 to 8 carbon atoms, alkylsulphinyl having 1 to 8 carbon atoms, alkylsulphonyl having 1 to 8 carbon atoms, monoalkylamino having 1 to 8 carbon atoms, cycloalkylamino wherein the cycloalkyl group has 3 to 7 carbon atoms, aryloxy wherein the aryl portion contains 6 to 10 carbon atoms, arylthio wherein the aryl portion contains 6 to 10 carbon atoms, cycloalkyloxy wherein the cycloalkyl group has 3 to 7 carbon atoms, sulfo, sulfonylamino, acylamido, acyloxy or combinations thereof; and   Het is a heterocyclic group, which is fully saturated, partially saturated or fully unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, aryl having 6 to 10 carbon atoms, alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, cyano, trifluoromethyl, nitro, oxo, amino, monoalkylamino having 1 to 8 carbon atoms, dialkylamino wherein each alkyl group has 1 to 8 carbon atoms, or combinations thereof.   
     
     
         43 . A compound according to  claim 6 , wherein:
 Ar is an aryl group containing 6 to 10 carbon atoms which is unsubstituted or substituted one or more times by alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, halogen, dialkylamino wherein the alkyl portions each have 1 to 8 carbon atoms, amino, cyano, hydroxyl, nitro, halogenated alkyl having 1 to 8 carbon atoms, halogenated alkoxy having 1 to 8 carbon atoms, hydroxyalkyl having 1 to 8 carbon atoms, hydroxyalkoxy having 2 to 8 carbon atoms, alkenyloxy having 3 to 8 carbon atoms, alkylthio having 1 to 8 carbon atoms, alkylsulphinyl having 1 to 8 carbon atoms, alkylsulphonyl having 1 to 8 carbon atoms, monoalkylamino having 1 to 8 carbon atoms, cycloalkylamino wherein the cycloalkyl group has 3 to 7 carbon atoms, aryloxy wherein the aryl portion contains 6 to 10 carbon atoms, arylthio wherein the aryl portion contains 6 to 10 carbon atoms, cycloalkyloxy wherein the cycloalkyl group has 3 to 7 carbon atoms, sulfo, sulfonylamino, acylamido, acyloxy or combinations thereof; and   Het is a heterocyclic group, which is fully saturated, partially saturated or fully unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, aryl having 6 to 10 carbon atoms, alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, cyano, trifluoromethyl, nitro, oxo, amino, monoalkylamino having 1 to 8 carbon atoms, dialkylamino wherein each alkyl group has 1 to 8 carbon atoms, or combinations thereof.   
     
     
         44 . A compound according to  claim 1 , wherein:
 Ar is an aryl group containing 6 to 10 carbon atoms which is unsubstituted or substituted one or more times by alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, halogen, dialkylamino wherein the alkyl portions each have 1 to 8 carbon atoms, amino, cyano, hydroxyl, nitro, halogenated alkyl having 1 to 8 carbon atoms, halogenated alkoxy having 1 to 8 carbon atoms, hydroxyalkyl having 1 to 8 carbon atoms, hydroxyalkoxy having 2 to 8 carbon atoms, alkenyloxy having 3 to 8 carbon atoms, alkylthio having 1 to 8 carbon atoms, alkylsulphinyl having 1 to 8 carbon atoms, alkylsulphonyl having 1 to 8 carbon atoms, monoalkylamino having 1 to 8 carbon atoms, cycloalkylamino wherein the cycloalkyl group has 3 to 7 carbon atoms and is optionally substituted by C 1-4 -alkyl, C 1-4 -alkoxy, hydroxyl, amino, monoalkylamino having 1 to 4 carbon atoms, and/or dialklyamino in which each alkyl group has 1 to 4 carbon atoms, aryloxy wherein the aryl portion contains 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, or C 1-4 -alkoxy-carbonyl, arylthio wherein the aryl portion contains 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, or C 1-4 -alkoxy-carbonyl, cycloalkyloxy wherein the cycloalkyl group has 3 to 7 carbon atoms and is optionally substituted by C 1-4 -alkyl, C 1-4 -alkoxy, hydroxyl, amino, monoalkylamino having 1 to 4 carbon atoms, and/or dialklyamino in which each alkyl group has 1 to 4 carbon atoms, sulfo, sulfonylamino, or combinations thereof; and   Het is a heterocyclic group, which is fully saturated, partially saturated or fully unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, aryl having 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, or C 1-4 -alkoxy-carbonyl, alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, cyano, trifluoromethyl, nitro, oxo, amino, monoalkylamino having 1 to 8 carbon atoms, dialkylamino wherein each alkyl group has 1 to 8 carbon atoms, or combinations thereof.   
     
     
         45 . A compound according to  claim 6 , wherein:
 Ar is an aryl group containing 6 to 10 carbon atoms which is unsubstituted or substituted one or more times by alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, halogen, dialkylamino wherein the alkyl portions each have 1 to 8 carbon atoms, amino, cyano, hydroxyl, nitro, halogenated alkyl having 1 to 8 carbon atoms, halogenated alkoxy having 1 to 8 carbon atoms, hydroxyalkyl having 1 to 8 carbon atoms, hydroxyalkoxy having 2 to 8 carbon atoms, alkenyloxy having 3 to 8 carbon atoms, alkylthio having 1 to 8 carbon atoms, alkylsulphinyl having 1 to 8 carbon atoms, alkylsulphonyl having 1 to 8 carbon atoms, monoalkylamino having 1 to 8 carbon atoms, cycloalkylamino wherein the cycloalkyl group has 3 to 7 carbon atoms and is optionally substituted by C 1-4 -alkyl, C 1-4 -alkoxy, hydroxyl, amino, monoalkylamino having 1 to 4 carbon atoms, and/or dialklyamino in which each alkyl group has 1 to 4 carbon atoms, aryloxy wherein the aryl portion contains 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, or C 1-4 -alkoxy-carbonyl, arylthio wherein the aryl portion contains 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, or C 1-4 -alkoxy-carbonyl, cycloalkyloxy wherein the cycloalkyl group has 3 to 7 carbon atoms and is optionally substituted by C 1-4 -alkyl, C 1-4 -alkoxy, hydroxyl, amino, monoalkylamino having 1 to 4 carbon atoms, and/or dialklyamino in which each alkyl group has 1 to 4 carbon atoms, sulfo, sulfonylamino, or combinations thereof; and   Het is a heterocyclic group, which is fully saturated, partially saturated or fully unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, aryl having 6 to 10 carbon atoms and is optionally substituted by halogen, C 1-4 -alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4 -alkylamino, dialkylamino in which each alkyl group has 1 to 4 carbon atoms, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, or C 1-4 -alkoxy-carbonyl, alkyl having 1 to 8 carbon atoms, alkoxy having 1 to 8 carbon atoms, cyano, trifluoromethyl, nitro, oxo, amino, monoalkylamino having 1 to 8 carbon atoms, dialkylamino wherein each alkyl group has 1 to 8 carbon atoms, or combinations thereof.   
     
     
         46 . A compound according to  claim 44 , wherein R 2  is H or methyl. 
     
     
         47 . A compound according to  claim 45 , wherein R 2  is H or methyl. 
     
     
         48 . A compound according to  claim 1 , wherein R 1  is H, F, Cl, Br, I, OH, CN, nitro, NH 2 , alkyl having 1 to 4 carbon atoms, fluorinated alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, alkoxy having 1 to 4 carbon atoms, cycloalkoxy having 3 to 7 carbon atoms, cycloalkylalkoxy having 4 to 7 carbon atoms, alkylthio having 1 to 4 carbon atoms, fluorinated alkoxy having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, hydroxyalkoxy having 2 to 4 carbon atoms, monoalkylamino having 1 to 4 carbon atoms, or dialkylamino wherein each alkyl group independently has 1 to 4 carbon atoms. 
     
     
         49 . A compound according to  claim 48 , wherein R 2  is H or methyl. 
     
     
         50 . A compound according to  claim 6 , wherein R 1  is H, F, Cl, Br, I, OH, CN, nitro, NH 2 , alkyl having 1 to 4 carbon atoms, fluorinated alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, alkoxy having 1 to 4 carbon atoms, cycloalkoxy having 3 to 7 carbon atoms, cycloalkylalkoxy having 4 to 7 carbon atoms, alkylthio having 1 to 4 carbon atoms, fluorinated alkoxy having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, hydroxyalkoxy having 2 to 4 carbon atoms, monoalkylamino having 1 to 4 carbon atoms, or dialkylamino wherein each alkyl group independently has 1 to 4 carbon atoms. 
     
     
         51 . A compound according to  claim 50 , wherein R 2  is H or methyl. 
     
     
         52 . A compound according to  claim 1 , wherein R 1  is H, F, Cl, Br, I, OH, CN, nitro, NH 2 , alkyl having 1 to 4 carbon atoms, fluorinated alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, alkoxy having 1 to 4 carbon atoms, cycloalkoxy having 3 to 7 carbon atoms, cycloalkylalkoxy having 4 to 7 carbon atoms, alkylthio having 1 to 4 carbon atoms, fluorinated alkoxy having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, hydroxyalkoxy having 2 to 4 carbon atoms, monoalkylamino having 1 to 4 carbon atoms, or dialkylamino wherein each alkyl group independently has 1 to 4 carbon atoms. 
     
     
         53 . A compound according to  claim 52 , wherein R 2  is H or methyl. 
     
     
         54 . A compound according to  claim 6 , wherein R 1  is H, F, Cl, Br, I, OH, CN, nitro, NH 2 , alkyl having 1 to 4 carbon atoms, fluorinated alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, alkoxy having 1 to 4 carbon atoms, cycloalkoxy having 3 to 7 carbon atoms, cycloalkylalkoxy having 4 to 7 carbon atoms, alkylthio having 1 to 4 carbon atoms, fluorinated alkoxy having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, hydroxyalkoxy having 2 to 4 carbon atoms, monoalkylamino having 1 to 4 carbon atoms, or dialkylamino wherein each alkyl group independently has 1 to 4 carbon atoms. 
     
     
         55 . A compound according to  claim 54 , wherein R 2  is H or methyl. 
     
     
         56 . A compound according to  claim 1 , wherein R 1  is alkyl having 1 to 4 carbon atoms, fluorinated alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, fluorinated alkoxy having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, or hydroxyalkoxy having 2 to 4 carbon atoms 
     
     
         57 . A compound according to  claim 56 , wherein R 2  is H or methyl. 
     
     
         58 . A compound according to  claim 6 , wherein R 1  is alkyl having 1 to 4 carbon atoms, fluorinated alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, fluorinated alkoxy having 1 to 4 carbon atoms, hydroxyalkyl having 1 to 4 carbon atoms, or hydroxyalkoxy having 2 to 4 carbon atoms 
     
     
         59 . A compound according to  claim 58 , wherein R 2  is H or methyl. 
     
     
         60 . A compound according to  claim 1 , wherein said compound is 1-Methyl-1H-Indazole-3-carboxamide, N-1-aza-bicyclo[2,2,2]oct-3-yl or a pharmaceutically acceptable salt thereof. 
     
     
         61 . A compound according to  claim 1 , wherein said compound is (R) 1-Methyl-1H-Indazole-3-carboxamide, N-1-aza-bicyclo[2,2,2]oct-3-yl or a pharmaceutically acceptable salt thereof. 
     
     
         62 . A compound according to  claim 1 , wherein said compound is (S) 1-Methyl-1H-Indazole-3-carboxamide, N-1-aza-bicyclo[2,2,2]oct-3-yl or a pharmaceutically acceptable salt thereof. 
     
     
         63 . A compound according to  claim 1 , wherein said compound is N-((3R)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(bromo)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         64 . A compound according to  claim 1 , wherein said compound is N-((3R)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(furan-3-yl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         65 . A compound according to  claim 1 , wherein said compound is N-((3R)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(phenyl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         66 . A compound according to  claim 1 , wherein said compound is N-((3R)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(thiophen-2-yl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         67 . A compound according to  claim 1 , wherein said compound is N-((3R)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(thiophen-3-yl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         68 . A compound according to  claim 1 , wherein said compound is N-((3S)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(bromo)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         69 . A compound according to  claim 1 , wherein said compound is N-((3S)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(furan-3-yl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         70 . A compound according to  claim 1 , wherein said compound is N-((3S)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(phenyl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         71 . A compound according to  claim 1 , wherein said compound is N-((3S)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(thiophen-2-yl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         72 . A compound according to  claim 1 , wherein said compound is N-((3S)-1-Azabicyclo[2.2.2]oct-3-yl)-6-(thiophen-3-yl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt thereof. 
     
     
         73 . A compound according to  claim 1 , wherein said compound is 1-Aza-bicyclo[2,2,2]oct-3-ylcarboxamide, N-1H-indazol-3-yl or a pharmaceutically acceptable salt thereof. 
     
     
         74 . A compound according to  claim 1 , wherein said compound is (S) 1-Aza-bicyclo[2,2,2]oct-3-ylcarboxamide, N-1H-indazol-3-yl or a pharmaceutically acceptable salt thereof. 
     
     
         75 . A compound according to  claim 1 , wherein said compound is (R) 1-Aza-bicyclo[2,2,2]oct-3-ylcarboxamide, N-1H-indazol-3-yl or a pharmaceutically acceptable salt thereof.