Heteroaryl substituted fused bicyclic heteroaryl compounds as GABAA receptor ligands

Abstract

This invention relates to heteroaryl substituted fused bicyclic heteroaryl compounds, such as heteroaryl substituted imidazopyridines, imidazopyrazines, imidazopyridizines, imidazopyrimidines, and imidazothiazoles, which may be described by Formula I or Formula II: The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABA A receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Processes for preparing compounds of Formula I and Formula II are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I or Formula II in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABA A receptors in tissue sections.

1 . A compound of the formula:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein: 
 Z 1  is nitrogen or CR 1 ;  
 Z 2  is nitrogen or CR 2 ;  
 Z 3  is nitrogen or CR 3 ;  
 Z 4  is nitrogen or CR 4 ;  
 Z 5  is nitrogen or carbon;  
 Z 6  is nitrogen or carbon; 
 provided that no more than two of Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , and Z 6  are nitrogen;  
 
 R 1 , R 2 , R 3 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano, amino, haloalkyl, and haloalkoxy;  
 (ii) alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, (cycloalkyl)alkyl, —NH(R 10 ), —N(R 10 )(R 11 ), hydroxyalkyl, aminoalkyl, (R 10 )NHalkyl, (R 10 )(R 11 )Nalkyl, alkanoyl, alkoxycarbonyl, alkylsulfonyl, (C 1 -C 6 )alkylsulfinyl, alkylthio, mono- and dialkylaminocarbonyl, heterocycloalkyl, aryl, and heteroaryl, each of which is unsubstituted or substituted with 1, 2, 3, or 4 substituents independently selected from R 20 ;  
 (iii) groups of the formula:  
                     wherein G is alkyl, —O—, —C(═O)—, or CH 2 —C(═O)—, and    R A  is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is unsubstituted or substituted with 1, 2, 3, or 4 of R 20 ;    
 (iv) groups of the formula:  
                     
 wherein J is N, CH, or C-alkyl, and  
 R B  and R C  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, (cycloalkyl)alkyl, heterocycloalkyl, aryl, arylalkyl, alkanoyl, heteroaryl, and mono and dialkylaminoalkyl, each of which is unsubstituted or substituted with 1 or 2 substituents independently chosen from halogen, hydroxy, cyano, amino, nitro, alkoxy, haloalkoxy, alkyl and haloalkyl; or  
 R B  and R C  and the atom to which they are attached form a 4- to 10-membered monocyclic or bicyclic ring, comprising: 
 a) 0, 1, 2 or 3 double bonds, and  
 b) 0, 1, 2 or 3 of oxo, O, S, SO, SO 2 , or N—R D , wherein R D  is (1)hydrogen; or  
 (2) Ar 1 , alkyl, cycloalkyl, heterocycloalkyl, or Ar 1 alkyl; wherein Ar 1  is aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently chosen from halogen, hydroxy, cyano, amino, nitro, alkoxy, and alkyl; and  
 
 (v) —OC(═O)R E , —C(═O)NH 2 , —C(═O)NHR E , —C(═O)NR E R F , —S(O) n R E , —S(O) n NH 2 , —S(O) n NHR E , —S(O) n NR E R F , —NHC(═O)R E , —C(═NR E )R F , —HC═N—OH, —HC═N(alkoxy), —HC═N(alkyl), —NR E C(═O)R F , —NHS(O) n R E , and —NR E S(O) n R F , wherein n is 0, 1 or 2;  
 
 R E  and R F  are independently selected at each occurrence from alkyl, cycloalkyl, heterocycloalkyl, alkoxy, mono- and dialkylamino, aryl, and heteroaryl, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from R 30 ;  
 R 5  represents: 
 (i) hydrogen, halogen, cyano, or haloalkyl;  
 (ii) alkyl, cycloalkyl, (cycloalkyl)alkyl, each of which comprises from 0 to 3 double bonds and/or from 0 to 3 triple bonds, and is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from R 30 ; or  
 (iii) aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of haloalkyl, amino, —NH(R 10 ), —N(R 10 )(R 11 ), carboxamido, (R 10 )NHcarbonyl, (R 10 )(R 11 )Ncarbonyl, halogen, hydroxy, nitro, cyano, amino, alkyl, alkoxy, alkoxy substituted with amino or mono- or dialkylamino, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkyloxy, heterocycloalkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aminoalkyl, and mono- and dialkylaminoalkyl;  
 
 R 10  and R 1 , are independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, alkanoyl, and mono and dialkylaminoalkyl;  
 Q represents —C(R 6 )(R 7 ), —N(alkyl)- or oxygen, wherein R 6  and R 7  independently represent hydrogen, fluorine, or alkyl; with the proviso that Q is not oxygen when X 2  is nitrogen;  
 R 20  is independently selected at each occurrence from: halogen, hydroxy, nitro, cyano, amino, alky, alkoxy, alkoxy substituted with amino or mono- or dialkylamino, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, alkenyl, alkynyl, haloalkyl, haloalkoxy, mono- and dialkylamino, aminoalkyl, and mono- and dialkylaminoalkyl;  
 R 30  is independently selected at each occurrence from: halogen, hydroxy, nitro, cyano, amino, alkyl, alkoxy; alkoxy substituted with amino or mono- or dialkylamino, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkyloxy, heterocycloalkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, mono- and dialkylamino, aminoalkyl, and mono- and dialkylaminoalkyl; and  
 the group:  
                     represents a 5 to 7 membered heteroaryl group containing from 1 to 4 heteroatoms independently selected from nitrogen, sulfur, and oxygen, unsubstituted or substituted at each carbon atom by R, and unsubstituted or substituted at each nitrogen atom available for substitution by R′, wherein    R is independently chosen at each occurrence from halogen, amino, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, (cycloalkyl)alkyl, haloalkyl, haloalkoxy, carboxamido, and 3- to 7-membered carbocyclic and heterocyclic rings, each of which is unsubstituted or substituted with one or more substituents independently selected from halogen, oxo, hydroxy, alkyl, and alkoxy;    R′ is independently chosen at each occurrence from alkyl, cycloalkyl, cycloalkyl(alkyl), and 3- to 7-membered carbocyclic and heterocyclic rings, each of which unsubstituted or substituted with one or more substituents independently selected from halogen, oxo, hydroxy, alkyl, and alkoxy;    X 1  and X 2  independently represent nitrogen, carbon or CH;    Y is nitrogen, carbon, —CH—, —CH 2 —, or absent; and    W represents aryl or heteroaryl, each of which is unsubstituted or substituted with from 0 to 4 groups independently selected from R 30 , —C(═O)OR E , —C(═O)NR E , —C(O)R E , —OR E  and —S(O) m R E , wherein m is 0, 1, or 2.    
 
   
   
       2 . A compound or salt according to  claim 1 , wherein 
 R 1 , R 2 , R 3 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano, amino, halo(C 1 -C 6 ) alkyl, and halo(C 1 -C 6 )alkoxy,  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, ((C 3 -C 8 )cycloalkyl)(C 1 -C 4 )alkyl, —NH(R 10 ), —N(R 10 )(R 11 ), hydroxy(C 1 -C 6 )alkyl, amino(C 1 -C 6 )alkyl, (R 10 )NH—, (C 1 -C 6 )alkyl, (R 10 )(R 11 )N(C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, 
 (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkylsulfonyl, (C 1 -C 6 )alkylsulfinyl, (C 1 -C 6 )alkylthio, mono- and di(C 1 -C 6 )alkylaminocarbonyl, and 3- to 8-membered heterocycloalkyl, aryl, and heteroaryl, each of which is unsubstituted or substituted with 1, 2, 3, or 4 substituents independently selected from R 20 ;  
 
 (iii) groups of the formula:  
                     wherein G is (C 1 -C 6 )alkyl, —O—, —C(═O)—, or —CH 2 —C(═O)—, and    R A  is 3- to 8-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is unsubstituted or substituted with 1, 2, 3, or 4 of R 20 ;    
 (iv) groups of the formula:  
                     wherein J is N, CH, or C—(C 1 -C 6 )alkyl and    R B  and R C  are each independently selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 cycloalkyl) (C 1 -C 4 )alkyl, 3- to 8-membered heterocycloalkyl, aryl, aryl(C 1 -C 4 )alkyl, (C 1 -C 6 )alkanoyl, 3- to 8-membered heteroaryl, and mono and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or 2 substituents independently chosen from halogen, hydroxy, cyano, amino, nitro, C 1 -C 6 alkoxy, halo(C 1 -C 6 )alkoxy, C 1 -C 6 alkyl and halo(C 1 -C 6 )alkyl; or    R B  and R C  and the atom to which they are attached form a 4- to 10-membered monocyclic or bicyclic ring, comprising: 
 a) 0, 1, 2 or 3 double bonds, and  
 b) 0, 1, 2 or 3 of oxo; O, S, SO, SO 2 , or N—R D , wherein R D  is (1) hydrogen; or (2) Ar 1 , (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, 3- to 8-membered heterocycloalkyl, or Ar 1 (C 1 -C 6 )alkyl wherein Ar 1  is aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently chosen from halogen, hydroxy, cyano, amino, nitro, C 1 -C 6 alkoxy, and C 1 -C 6 alkyl; and  
   
 (v) —OC(═O)R E , —C(═O)NH 2 , —C(═O)NHR E , —C(═O)NR E R F , —S(O) n R E , —S(O) n NH 2 , —S(O) n NHR E , —S(O) n NR E R F , —NHC(═O)R E , —C(═NR E )R F , —HC═N—OH, —HC═N(C 1 -C 6 alkoxy), —HC═N(C 1 -C 6 alkyl), —NR E C(═O)R F , —NHS(O) n R E , and —NR E S(O) n R F , wherein n is 0, 1 or 2, 
 R E  and R F  are independently selected at each occurrence from (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, 3- to 8-membered heterocycloalkyl, (C 1 -C 6 )alkoxy, mono- and di(C 1 -C 6 )alkylamino, aryl, and 3- to 8-membered heteroaryl, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from R 30 ;  
 
   R 5  represents: 
 (i) hydrogen, halogen or cyano;  
 (ii) (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 cycloalkyl)(C 1 -C 4 )alkyl, or an analogue of the foregoing that comprises from 1 to 3 double bonds and/or from 1 to 3 triple bonds, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from R 30 ; or  
 (iii) 3- to 8-membered aryl, 3- to 8-membered aryl(C 1 -C 4 )alkyl, 3- to 8-membered heteroaryl, or 3- to 8-membered heteroaryl(C 1 -C 4 )alkyl, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo(C 1 -C 6 alkyl, amino, —NH(R 10 ), —N(R 10 )(R 11 ), carboxamido, (R 10 )NHcarbonyl, (R 10 )(R 11 )Ncarbonyl, halogen, hydroxy, nitro, cyano, amino, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy substituted with amino or mono- or di(C 1 -C 6 )alkylamino, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkoxy, heterocyclo(C 1 -C 4 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl;  
   R 10  and R 1 , are independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkylalkyl, aryl, aryl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, and mono and di(C 1 -C 6 )alkylaminoalkyl;    R 20  is independently selected at each occurrence from the group consisting of halogen, hydroxy, nitro, cyano, amino, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy substituted with amino or mono- or di(C 1 -C 6 )alkylamino, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono- and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl;    R 30  is independently selected at each occurrence from halogen, hydroxy, nitro, cyano, amino, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy substituted with amino or mono- or di(C 1 -C 6 )alkylamino, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkoxy, 3- to 8-membered heterocycloalkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono- and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl;    Q represents C(R 6 )(R 7 ), N(C 1 -C 6 alkyl) or oxygen, wherein R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6 alkyl; with the proviso that Q is not oxygen when X 2  is nitrogen;    R is independently chosen at each occurrence from halogen, amino, C 1 -C 6 alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, C 1 -C 6 alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 cycloalkyl)(C 1 -C 4 )alkyl, halo(C 1 -C 6 )alkyl, haloalkoxy, carboxamido, and 3- to 7-membered carbocyclic and heterocyclic rings, each of which is unsubstituted substituted with from 1 to 4 substituents independently selected from halogen, oxo, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;    R′ is independently chosen at each occurrence from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl(C 1 -C 4 alkyl), and 3- to 7-membered carbocyclic and heterocyclic rings, each of which is unsubstituted or substituted with from 1 to 4 substituents independently selected from halogen, oxo, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy; and    W represents 3- to 8-membered aryl or heteroaryl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 , —C(═O)OR E , —C(═O)NR E , —C(O)R E , —OR E  and —S(O) m R E , wherein m is 0, 1, or 2.    
   
   
       3 . A compound or salt according to  claim 2  of the formula:  
     
       
         
         
             
             
         
       
     
     wherein X 3  and X 4  are independently selected from the group consisting of CH, CR, N, O, S, NH, and N(C 1 -C 6 )alkyl provided that at least one of X 1 , X 2 , X 3 , and X 4  is CH or CR; 
 and wherein R is independently chosen at each occurrence from: halogen, amino, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, carboxamido, and  3 - to 7-membered carbocyclic or heterocyclic rings, each of which is unsubstituted or substituted with from 1 to 4 substituents independently selected from halogen, oxo, hydroxy, (C 1 -C 4 )alkyl, and —O(C 1 -C 4 alkyl).  
 
   
   
       4 . A compound or salt according to  claim 3 , wherein Z 1  is CR 1 , Z 2  is CR 2 , Z 3  is CR 3 , and Z 4  is nitrogen.  
   
   
       5 . A compound or salt according to  claim 3 , wherein Z 1  is CR 1 , Z 2  is CR 2 , Z 3  is nitrogen, and Z 4  is CR 4 .  
   
   
       6 . A compound or salt according to  claim 3 , wherein Z 1  is CR 1 , Z 2  is nitrogen, Z 3  is CR 3  and Z 4  is CR 4 .  
   
   
       7 . A compound or salt according to  claim 3 , wherein Z 1  is nitrogen, Z 2  is CR 2 , Z 3  is CR 3  and Z 4  is CR 4 .  
   
   
       8 . A compound or salt according to  claim 3 , wherein X 2  is carbon and Q is oxygen.  
   
   
       9 . A compound or salt according to  claim 3 , wherein X 2  is carbon and Q is —NH—, or —N(C 1 -C 6 alkyl)-.  
   
   
       10 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       11 . A compound or salt according to  claim 10 , wherein Q is C(R 6 )(R 7 ).  
   
   
       12 . A compound or salt according to  claim 11 , wherein 
 each R is independently selected from the group consisting of: 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 1 , R 2 , R 3 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6  alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .    
   
   
       13 . A compound or salt according to  claim 3  of the formula  
     
       
         
         
             
             
         
       
     
   
   
       14 . A compound or salt according to  claim 13 , wherein Q is C(R 6 )(R 7 ).  
   
   
       15 . A compound or salt according to  claim 14 , wherein: 
 each R is independently selected from the group consisting of: 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 1 , R 2 , R 3 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3- C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6 alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .    
   
   
       16 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       17 . A compound or salt according to  claim 16 , wherein Q is C(R 6 )(R 7 ).  
   
   
       18 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       19 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       20 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       21 . A compound or salt according to  claim 20 , wherein Q is C(R 6 )(R 7 ).  
   
   
       22 . A compound or salt according to  claim 2  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       23 . A compound or salt according to  claim 22 , wherein Q is C(R 6 )(R 7 ).  
   
   
       24 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       25 . A compound or salt according to  claim 3  of the formula  
     
       
         
         
             
             
         
       
     
   
   
       26 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       27 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       28 . A compound or salt according to  claim 27 , wherein Q is C(R 6 )(R 7 ).  
   
   
       29 . A compound or salt according to  claim 28 , wherein: 
 each R is independently selected from the group consisting of 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy, and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 1 , R 2 , R 3 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6 alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .    
   
   
       30 . A compound or salt according to  claim 29 , wherein R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl.  
   
   
       31 . A compound or salt according to  claim 30 , wherein 
 R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl; and    W represents phenyl, 2-thiazoyl, or 2-pyridyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .    
   
   
       32 . A compound or salt according to  claim 31 , wherein R 1  and R 4  are independently selected from hydrogen, halogen, methyl, ethyl, methoxy, and ethoxy.  
   
   
       33 . A compound or salt according to  claim 3  of the formula  
     
       
         
         
             
             
         
       
     
   
   
       34 . A compound or salt according to  claim 33 , wherein Q is C(R 6 )(R 7 ).  
   
   
       35 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       36 . A compound or salt according to  claim 35  wherein Q is C(R 6 )(R 7 ).  
   
   
       37 . A compound or salt according to  claim 36 , wherein: 
 each R is independently selected from the group consisting of 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy, and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 1 , R 2 , and R 3  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3- C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6 alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .    
   
   
       38 . A compound or salt according to  claim 37 , wherein R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl.  
   
   
       39 . A compound or salt according to  claim 38 , wherein: 
 each R is independently selected from the group consisting of 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy, and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 1 , R 2 , and R 3  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6 alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .    
   
   
       40 . A compound or salt according to  claim 39 , wherein R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl.  
   
   
       41 . A compound or salt according to  claim 40 , wherein W represents phenyl, 2-thiazoyl, or 2-pyridyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .  
   
   
       42 . A compound or salt according to  claim 39  wherein R 1  is selected from hydrogen, halogen, methyl, ethyl, methoxy, and ethoxy.  
   
   
       43 . A compound or salt according to  claim 3  of the formula  
     
       
         
         
             
             
         
       
     
   
   
       44 . A compound or salt according to  claim 43 , wherein Q is C(R 6 )(R 7 ).  
   
   
       45 . A compound or salt according to  claim 3  of the formula  
     
       
         
         
             
             
         
       
     
   
   
       46 . A compound or salt according to  claim 45 , wherein Q is C(R 6 )(R 7 ).  
   
   
       47 . A compound or salt according to  claim 46 , wherein: 
 each R is independently selected from the group consisting of 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy, and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 2 , R 3 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3- C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6 alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .    
   
   
       48 . A compound or salt according to  claim 47 , wherein R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl.  
   
   
       49 . A compound or salt according to  claim 48 , wherein W represents phenyl, 2-thiazoyl, or 2-pyridyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .  
   
   
       50 . A compound or salt according to  claim 47  wherein R 1  is selected from hydrogen, halogen, methyl, ethyl, methoxy, and ethoxy.  
   
   
       51 . A compound or salt according to  claim 3  of the formula  
     
       
         
         
             
             
         
       
     
   
   
       52 . A compound or salt according to  claim 51 , wherein Q is C(R 6 )(R 7 ).  
   
   
       53 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       54 . A compound or salt according to  claim 53 , wherein Q is C(R 6 )(R 7 ).  
   
   
       55 . A compound or salt according to  claim 54 , wherein: 
 each R is independently selected from the group consisting of 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy, and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 1 , R 2 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
   (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and 
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3- C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6  alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 R 30  groups.    
   
   
       56 . A compound or salt according to  claim 55 , wherein R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl.  
   
   
       57 . A compound or salt according to  claim 56 , wherein W represents phenyl, 2-thiazoyl, or 2-pyridyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .  
   
   
       58 . A compound or salt according to  claim 55 , wherein R 1  is selected from hydrogen, halogen, methyl, ethyl, methoxy, and ethoxy.  
   
   
       59 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       60 . A compound or salt according to  claim 59 , wherein Q is C(R 6 )(R 7 ).  
   
   
       61 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       62 . A compound or salt according to  claim 61 , wherein Q is C(R 6 )(R 7 ).  
   
   
       63 . A compound or salt according to  claim 62 , wherein: 
 each R is independently selected from the group consisting of 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy, and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 1 , R 3 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3- C 8 )cycloalkyl, or (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6  alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .    
   
   
       64 . A compound or salt according to  claim 63 , wherein R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl.  
   
   
       65 . A compound or salt according to  claim 64 , wherein W represents phenyl, 2-thiazoyl, or 2-pyridyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .  
   
   
       66 . A compound or salt according to  claim 63  wherein R 1  is selected from hydrogen, halogen, methyl, ethyl, methoxy, and ethoxy.  
   
   
       67 . A compound or salt according to  claim 3  of the formula:  
     
       
         
         
             
             
         
       
     
   
   
       68 . A compound or salt according to  claim 67 , wherein Q is C(R 6 )(R 7 ).  
   
   
       69 . A compound or salt according to  claim 68 , wherein: 
 each R is independently selected from the group consisting of 
 (i) hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl and halo(C 1 -C 6 )alkoxy, and  
 (ii) phenyl and pyridyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;  
   R 1 , R 2 , R 3 , and R 4  are independently selected from: 
 (i) hydrogen, halogen, hydroxy, nitro, cyano and amino;  
 (ii) (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkyl ether, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heteroaryl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, each of which is unsubstituted or substituted with 1 or substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy; and  
 (iii) groups of the formula  
                     wherein R A  is 5- to 7-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is unsubstituted or substituted with 1 or 2 substituents independently selected from hydroxy, halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy;    
   R 5  represents hydrogen, halogen, (C 1 -C 6 )alkyl, (C 3- C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl, benzyl, thiophenyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, or pyrimidinyl;    R 6  and R 7  independently represent hydrogen, fluorine, or C 1 -C 6  alkyl; and    W represents phenyl, thienyl, thiazolyl, pyridyl, imidazolyl, pyrazolyl, isoxazolyl, or pyrimidinyl, each of which is unsubstituted or substituted with from 1 to 4 R 30  groups.    
   
   
       70 . A compound or salt according to  claim 69 , wherein R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl.  
   
   
       71 . A compound or salt according to  claim 70 , wherein W represents phenyl, 2-thiazoyl, or 2-pyridyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .  
   
   
       72 . A compound or salt according to  claim 69 , wherein R 1  is selected from hydrogen, halogen, methyl, ethyl, methoxy, and ethoxy.  
   
   
       73 . A compound of the formula:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof wherein: 
 R 1  and R 2  are independently selected from hydrogen, halogen, nitro, cyano, haloalkyl, haloalkoxy, alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, (cycloalkyl)alkyl, mono and dialkylamino, and aminoalkyl;  
 R 5  represents: 
 (i) hydrogen, halogen, cyano, or haloalkyl;  
 (ii) alkyl, cycloalkyl, (cycloalkyl)alkyl, each of which comprises from 0 to 3 double bonds and/or from 0 to 3 triple bonds, and is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from R 30 ; or  
 (iii) aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of alkyl, haloalkyl, amino, —NH(R 10 ), —N(R 10 )(R 11 ), carboxamido, (R 10 )NHcarbonyl, (R 10 )(R 11 )Ncarbonyl, halogen, hydroxy, nitro, cyano, amino, alkoxy, haloalkoxy, alkoxy substituted with amino or mono- or di-alkylamino, cycloalkyl, (cycloalkyl)alkyl, (cycloalkyl)alkoxy, heterocycloalkyl, alkenyl, alkynyl, aminoalkyl, and mono- and di-alkylaminoalkyl;  
 
 Q represents C(R 6 )(R 7 ), N(alkyl) or oxygen, wherein R 6  and R 7  independently represent hydrogen, fluorine, or alkyl; with the proviso that Q is not oxygen when X 2  is nitrogen;  
 R 10  and R 11  are independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, alkanoyl, and mono and dialkylaminoalkyl;  
 R 30  is independently selected at each occurrence from halogen, hydroxy, nitro, cyano, amino, alkyl, alkoxy, alkoxy substituted with amino or mono- or dialkylamino, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkyloxy, heterocycloalkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, mono- and dialkylamino, aminoalkyl, and mono- and dialkylaminoalkyl;  
 the group:  
                     
  represents a 5 to 7 membered heteroaryl group containing from 1 to 4 heteroatoms independently selected from nitrogen, sulfur, and oxygen, wherein the ring is unsubstituted or substituted at each carbon atom by R, and unsubstituted or substituted at each nitrogen atom available for substitution by R′, wherein 
 R is independently chosen at each occurrence from halogen, amino, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, (cycloalkyl)alkyl, haloalkyl, haloalkoxy, carboxamido, and 3- to 7-membered carbocyclic and heterocyclic rings, each of which is unsubstituted or substituted with one or more substituents independently selected from halogen, oxo, hydroxy, alkyl, and alkoxy;  
 R′ is independently chosen at each occurrence from alkyl, cycloalkyl, cycloalkyl(alkyl), and 3- to 7-membered carbocyclic and heterocyclic rings, each of which is unsubstituted or substituted with one or more substituents independently selected from halogen, oxo, hydroxy, alkyl, and alkoxy;  
 
 X 1  and X 2  independently represent nitrogen, carbon or CH;  
 Y is nitrogen, carbon, —CH—, —CH 2 —, or absent; and  
 W represents aryl or heteroaryl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 , —CO 2 H, —C(═O)OR E , —C(═O)NR E , —C(O)R E , —OR E , and —S(O) m R E , wherein R E  is independently selected at each occurrence from alkyl, cycloalkyl, heterocycloalkyl, alkoxy, mono- and dialkylamino, aryl, and heteroaryl, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from R 30 , and wherein m is 0, 1, or 2.  
 
   
   
       74 . A compound or salt according to  claim 73 , wherein: 
 R 1  and R 2  are independently selected from hydrogen, halogen, nitro, cyano, halo(C 1- C 6 )alkyl, halo(C 1- C 6 )alkoxy, C 1- C 6 alkyl, C 1- C 6 alkoxy, C 3- C 7 cycloalkyl, C 2- C 6 alkenyl, C 2 -C 6 alkynyl, (C 3- C 7 )cycloalkyl) C 1- C 4 alkyl, mono and di(C 1- C 6 )alkylamino, and amino(C 1- C 6 )alkyl;    R 5  represents: 
 (i) hydrogen, halogen, cyano, or haloalkyl;  
 (ii) (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 cycloalkyl)(C 1 -C 4 )alkyl, each of which comprises from 0 to 3 double bonds and/or from 0 to 3 triple bonds, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from R 30 ; or  
 (iii) aryl, aryl(C 1 -C 4 )alkyl, 3- to 8-membered heteroaryl, or 3- to 8-membered heteroaryl(C 1 -C 4 )alkyl, each of which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, amino, —NH(R 10 ), —N(R 10 )(R 11 ), carboxamido, (R 10 )NHcarbonyl, (R 10 )(R 11 )Ncarbonyl, halogen, hydroxy, nitro, cyano, amino, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy substituted with amino or mono- or di(C 1 -C 6 )alkylamino, halo(C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl (C 1 -C 4 )alkoxy, heterocyclo(C 1 -C 4 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, amino(C 1 -C 6 ) alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl;  
   Q represents C(R 6 )(R 7 ), N(C 1 -C 6 alkyl) or oxygen, wherein R 6  and R 7  independently represent hydrogen, fluorine, or (C 1 -C 6 )alkyl; with the proviso that Q is not oxygen when X 2  is nitrogen;    R 10  and R 1 , are independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, aryl, aryl(C 1 -C 4 )alkyl, (C 1 -C 6 )alkanoyl, and mono and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl;    R 30  is independently selected at each occurrence from halogen, hydroxy, nitro, cyano, amino, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy substituted with amino or mono- or di(C 1 -C 6 )alkylamino, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkoxy, 3- to 8-membered heterocyclo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono- and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl;    R is independently chosen at each occurrence from halogen, amino, C 1 -C 6 alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, C 1 -C 6 alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 cycloalkyl)(C 1 -C 4 )alkyl, halo(C 1 -C 6 )alkyl, haloalkoxy, carboxamido, and 3- to 7-membered carbocyclic and heterocyclic rings, each of which is unsubstituted or substituted with from 1 to 4 substituents independently selected from halogen, oxo, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy;    R′ is independently chosen at each occurrence from C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl(C 1 -C 4 alkyl), and 3- to 7-membered carbocyclic and heterocyclic rings, each of which is unsubstituted or substituted with from 1 to 4 substituents independently selected from halogen, oxo, hydroxy, C 1 -C 4 alkyl, and C 1 -C 4 alkoxy; and    W represents 3- to 8-membered aryl or heteroaryl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 , —C(═O)OR E , —C(═O)NR E , —C(O)R E , —OR E  and —S(O) m R E , wherein m is 0, 1, or 2.    
   
   
       75 . A compound or salt according to  claim 74  of the formula  
     
       
         
         
             
             
         
       
     
     wherein R 5  represents hydrogen, halogen, or (C 1 -C 6 )alkyl, and R 6  and R 7  independently represent hydrogen or (C 1 -C 6 )alkyl.  
   
   
       76 . A compound or salt according to  claim 75 , wherein W represents phenyl, 2-thiazoyl, or 2-pyridyl, each of which is unsubstituted or substituted with from 1 to 4 groups independently selected from R 30 .  
   
   
       77 . A compound or salt according to  claim 76 , wherein R 1  and R 2  are independently selected from hydrogen, halogen, nitro, cyano, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, heterocycloalkyl, halo(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkoxy, mono and di(C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, and mono- and di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl.  
   
   
       78 . A pharmaceutical composition comprising a compound or salt according to  claim 1  or  claim 73  combined with a pharmaceutically acceptable carrier or excipient.  
   
   
       79 . A method for altering the signal-transducing activity of GABA A  receptors, said method comprising contacting a cell expressing GABA A  receptors with a solution comprising a compound or salt according to  claim 1  or  claim 78  at a concentration sufficient to detectably alter the electrophysiology of the cell, wherein a detectable alteration of the electrophysiology of the cell indicates an alteration of the signal-transducing activity of GABA A  receptors.  
   
   
       80 . A method for altering the signal-transducing activity of GABA A  receptors, said method comprising contacting cells expressing GABA A  receptors with a solution comprising a compound or salt according to  claim 1  or  claim 78  at a concentration sufficient to detectably alter the chloride conductance in vitro of the cell expressing GABA A  receptors.  
   
   
       81 . The method of  claim 80  wherein the cell is recombinantly expressing a heterologous GABA A  receptor and the alteration of the electrophysiology of the cell is detected by intracellular recording or patch clamp recording.  
   
   
       82 . The method of  claim 80  wherein the cell is a neuronal cell that is contacted in vivo in an animal, the solution is a body fluid, and the alteration in the electrophysiology of the cell is detected as a reproducible change in the animal's behavior.  
   
   
       83 . The method of  claim 82  wherein the animal is a human, the cell is a brain cell, and the fluid is cerebrospinal fluid.  
   
   
       84 . A method for altering the signal-transducing activity of GABA A  receptors, the method comprising exposing cells expressing the GABA A  receptors to a compound or salt according to  claim 1  or  claim 78  at a concentration sufficient to inhibit Ro15-1788 binding in vitro to cells expressing a cloned human GABA A  receptor.  
   
   
       85 . A method for the treatment of anxiety, depression, a sleep disorder, schizophrenia, attention deficit-hyperactivity disorder, or for the enhancement of memory comprising administering an effective amount of a compound or salt of  claim 1  or  claim 78  to a patient in need thereof.  
   
   
       86 . A method for demonstrating the presence of GABA A  receptors a cell or tissue sample, said method comprising: 
 contacting a cell or tissue sample with a labeled compound or salt according to  claim 1  or  claim 78;     washing the cell or tissue sample to remove unbound labeled compound or salt; and    detecting the presence of labeled compound of salt in the cell or tissue sample.    
   
   
       87 . The method of  claim 86  in which the cell or tissue sample is a tissue section.  
   
   
       88 . The method of  claim 86  in which the labeled compound or salt contains a radioactive label or a directly or indirectly luminescent label.  
   
   
       89 . The method of  claim 86  in which each measurement of the amount of labeled compound or salt in a sample is carried out by viewing the autoradiograms and the comparison is a comparison of the exposure density of the autoradiograms.  
   
   
       90 . A packaged pharmaceutical composition comprising the pharmaceutical composition of  claim 1  or  claim 78  in a container and further comprising at least one of: 
 instructions for using the composition to treat a patient suffering from an anxiety disorder, or    instructions for using the composition to treat a patient suffering from depression, or    instructions for using the composition to treat a patient suffering from a sleeping disorder,    instructions for using the composition to treat a patient suffering from schizophrenia, or    instructions for using the composition to treat a patient suffering from attention deficit-hyperactivity disorder.    
   
   
       91 . A packaged pharmaceutic composition comprising a pharmaceutical composition of  claim 1  or  claim 78  in a container and further comprising at least one of: 
 instructions for using the composition to treat a patient suffering from Alzheimer's dementia, or    instructions for using the composition to enhance memory in a patient.    
   
   
       92 . The use of a compound or salt according to  claim 1  or  claim 78  for the manufacture of a medicament for the treatment of anxiety, depression, a sleep disorder, schizophrenia, or attention deficit-hyperactivity disorder.  
   
   
       93 . The use of a compound or salt according to  claim 1  or  claim 78  for the manufacture of a medicament for the enhancement of memory.  
   
   
       94 . A compound according to  claim 1  or  claim 78  wherein in a assay of GABA A  receptor binding that determines the displacement of  3 H-Flumazenil from rat cortical tissue in 0.05 M Tris HCl buffer at 4° C. the compound exhibits an K i  of 1 micromolar or less.  
   
   
       95 . A compound according to  claim 94  wherein in a assay of GABA A  receptor binding the compound exhibits an K i  of 100 nanomolar or less.  
   
   
       96 . A compound according to  claim 94  wherein in a assay of GABA A  receptor binding the compound exhibits an K i  of 10 nanomolar or less.