2,4-Substituted pyridine derivatives

Abstract

Disclosed are compounds of the formula or pharmaceutically acceptable salts thereof wherein: represents: and A, B, G, D, E, R a , R b , W, and Z are defined herein. These compounds are agonists, antagonists or inverse agonists for GABA A brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABA A brain receptors and are therefore useful in the diagnosis and treatment of anxiety, depression, Down Syndrome, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABA A receptors in tissue samples.

What is claimed is:  
     
         1 ) A compound of the formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof wherein:  
       
         
           
           
               
               
           
         
       
       represents:  
       
         
           
           
               
               
           
         
       
       wherein: 
 A, B, D,and G are nitrogen or C-R 1 ;  
 with the proviso that not more than 2 of A, B, G, and D are nitrogen; and  
 E represents oxygen, sulfur or N-R 5 ;  
 R 1  at each occurrence is independently selected from the group consisting of hydrogen, halogen, cyano, haloalkyl, haloalkoxy, hydroxy, amino, —NH(R 2 ), —N(R 2 ) 2 , nitro, C 1 -C 8  alkoxy and R 2 ; wherein 
 R 2  at each occurrence is independently selected from the group consisting of C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, C 3 -C 8  cycloalkenyl, and C 5 -C 10  cycloalkynyl;  
 R 5  is selected from the group consisting of R 2 , aryl, and C 1 -C 8  alkoxy 1 , wherein R 2 , the aryl group and the C 1 -C 8  alkoxy, areoptionally substituted with 1, 2, 3, or 4 groups selected from the group consisting of hydroxy, cyano, halogen, nitro, haloalkyl, haloalkoxy, amino, —NH(R 2 ), and —N(R 2 ) 2 ;  
 
 R a  and R b  at each occurrence are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, haloalkyl, haloalkoxy, hydroxy, amino, —OR 2  wherein R 2  is substituted with 0-2 R 6 , —NH(R 2 ) wherein R 2  is substituted with 0-2 R 6 , —N(R 2 ) 2  wherein the R 2  groups are independently substituted with 0-2 R 6 , R 2  wherein the R 2  group is substituted with 0-2 R 6 , phenyl substituted with 0-3 R 6 , —XR 7 , and Y; 
 W represents phenyl, pyrrolyl, furanyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, pyrazinyl, benzimidazolyl, naphthyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzo[b]thiophenyl, benz[d]isoxazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, or quinoxalinyl, wherein each is substituted with R d , R d ′, and R d ″ which are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, haloalkyl, haloalkoxy, hydroxy, amino, R 2  substituted with 0-2 R 6 , —OR 2  substituted with 0-2 R 6 , —NH(R 2 ) wherein R 2  is substituted with 0-2 R 6 , phenyl substituted with 0-3 R 6 , —XR 7 , Y, and —N(C 1 -C 6  alkyl 1 )(C 1 -C 6  alkyl 2 ) where each alkyl is independently substituted with 0-2 R 6 , or alkyl 1 , alkyl 2  and the nitrogen to which they are attached form a heterocycloalkyl ring substituted with 0-2 R 6 ;  
 X at each occurrence is independently selected from the group consisting of —CH 2 —, —CHR 8 —, —O—, —S(O) m —, —NH—, —NR 8 —, —C(O)—, —C(O)O—, —C(O)NH—, —C(O)NR 8 —, —S(O) m NH—, —S(O) m NR 8 —, —NHC(O)—, —NR 8 C(O)—, —NHS(O) m —, and —NR 8 S(O) m —; wherein m is 0, 1, or 2;  
 R 6  at each occurrence is independently selected from the group consisting of halogen, hydroxy, R 2 , —OR 2 , —NH(R 2 ), —N(R 2 ) 2 , —NH—(R 2 —Y), —N(R 2 )—(R 2 —Y), —NH—(R 2 —N(R 2 )(R 2 )), —N(R 2 )—(R 2 —N(R 2 )(R 2 )), morpholinyl, pyrrolidinyl, piperidinyl, thiomorpholinyl, piperazinyl, homopiperazinyl, —S(O) m (R 2 ), haloalkyl, haloalkoxy, —CO(R 2 ), —CONH(R 2 ), CON(R 2 ) 2 , —XR 7 , and Y; 
 wherein m is 0, 1, or 2;  
 
 R 7  and R 8  at each occurrence independently carry the same definition as R 2 , wherein R 7  and R 8  are substituted with 0, 1, 2, 3, or 4 substituents selected from the group consisting of oxo, hydroxy, halogen, amino, cyano, nitro, haloalkyl, haloalkoxy, —O(R 2 ), —NH(R 2 ), —N(R 2 ) 2 , —NHC(O)(R 2 ), —N(R 2 )C(O)(R 2 ), —NHS(O) m (R 2 ), —S(O) m (R 2 ), —S(O) m NH(R 2 ), and —S(O) m N(R 2 ) 2 , and Y′; 
 wherein m is 0, 1, or 2;  
 
 Y and Y′ at each occurrence are independently selected from 5- to 8-membered carbocycles or heterocycles, which are saturated, partially unsaturated, or aromatic, and contain zero, one or two heteroatoms selected from N, O, and S, and which carbocycles or heterocycles may be further substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, hydroxy, amino, nitro, cyano, R 2 , —OR 2 , —NH(R 2 ), —N(R 2 ) 2 , and —S(O) a (R 2 ); wherein 
 a is 0, 1, or 2; and  
 
 
 Z is (CR a R b ) n , wherein n is 0, 1, or 2.  
 
     
     
         2 . A compound of the formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof wherein:  
       
         
           
           
               
               
           
         
       
       represents:  
       
         
           
           
               
               
           
         
       
       wherein: 
 A, B, D, and G are nitrogen or C-R 1 ;  
 with the proviso that not more than 2 of A, B, G, and D are nitrogen; and  
 E represents oxygen, sulfur or N-R 5 ;  
 R 1  at each occurrence is independently selected from the group consisting of hydrogen, C 1 -C 6  alkyl, halogen, cyano, haloalkyl, haloalkoxy, hydroxy, amino, —NH(C 1 -C 6  alkyl), and —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl); 
 R 5  is selected from the group consisting of C 1 -C 6  alkyl, aryl, and C 1 -C 6  alkoxy, wherein the C 1 -C 6  alkyl, the aryl group, and the C 1 -C 6  alkoxy are optionally substituted with 1, 2, 3, or 4 groups selected from the group consisting of hydroxy, cyano, halogen, nitro, haloalkyl, haloalkoxy, amino, —NH(C 1 -C 6  alkyl), and —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl);  
 
 R a  and R b  at each occurrence are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, haloalkyl, haloalkoxy, hydroxy, amino, C 1 -C 6  alkoxy substituted with 0-2 R 6 , —NH(C 1 -C 6  alkyl) wherein the C 1 -C 6  alkyl group is substituted with 0-2 R 6 , —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl) wherein the C 1 -C 6  alkyl groups are independently substituted with 0-2 R 6 , C 1 -C 6  alkyl wherein the C 1 -C 6  alkyl group is substituted with 0-2 R 6 , phenyl substituted with 0-3 R 6 , —XR 7 , and Y;  
 W represents phenyl, pyrrolyl, furanyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, pyrazinyl, benzimidazolyl, naphthyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzo[b]thiophenyl, benz[d]isoxazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, or quinoxalinyl, wherein each is substituted with R d , R d ′, and R d ″ which are independently selected from the group consisting of 
 hydrogen, halogen, cyano, nitro, haloalkyl, haloalkoxy, hydroxy, amino, C 1 -C 6  alkyl substituted with 0-2 R 6 , C 1 -C 6  alkoxy substituted with 0-2 R 6 , —NH(C 1 -C 6  alkyl) wherein the C 1 -C 6  alkyl is substituted with 0-2 R 6 , phenyl substituted with 0-3 R 6 , —XR 7 , Y, and —N(C 1 -C 6  alkyl 1 )(C 1 -C 6  alkyl 2 ) wherein alkyl 1  and alkyl 2  are independently substituted with 0-2 R 6 , or 
 alkyl 1 , alkyl 2  and the nitrogen to which they are attached form a heterocycloalkyl ring substituted with 0-2 R 6 ;  
 
 X at each occurrence is independently selected from the group consisting of —CH 2 —, —CHR 8 —, —O—, —S(O) m —, —NH—, —NR 8 —, —C(O)—, —C(O)O—, —C(O)NH—, —C(O)NR 8 —, —S(O) m NH—, —S(O) m NR 8 —, —NHC(O)—, —NR 8 C(O)—, —NHS(O) m —, and —NR 8 S(O) m —; wherein m is 0, 1, or 2;  
 R 6  at each occurrence is independently selected from the group consisting of halogen, hydroxy, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), —NH—(C 1 -C 6  alkyl-Y), —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-Y), —NH—(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)), —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)), morpholinyl, pyrrolidinyl, piperidinyl, thiomorpholinyl, piperazinyl, homopiperazinyl, —S(O) m (C 1 -C 6  alkyl), haloalkyl, haloalkoxy, —CO(C 1 -C 6  alkyl), —CONH(C 1 -C 6  alkyl), CON(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), —XR 7 , and Y; wherein 
 m is 0, 1, or 2;  
 
 R 7  and R8 at each occurrence are independently C 1 -C 8  alkyl, wherein R 7  and R 8  are substituted with 0, 1, 2, 3, or 4 substituents selected from the group consisting of oxo, hydroxy, halogen, amino, cyano, nitro, haloalkyl, haloalkoxy, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), —NHS(O) m (C 1 - 6  alkyl), —S(O) m (C 1 -C 6  alkyl), —S(O) m NH(C 1 -C 6  alkyl), and —S(O) m N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), and Y′; 
 wherein m is .0, 1, or 2; and  
 
 Y and Y′ at each occurrence are independently selected from 5- to 8-membered carbocycles or heterocycles, which are saturated, partially unsaturated, or aromatic, and contain zero, one or two heteroatoms selected from N, O, and S, and which carbocycles or heterocycles may be further substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, hydroxy, amino, nitro, cyano, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), and —S(O) a (C 1 -C 6  alkyl); wherein 
 a is 0, 1, or 2; and  
 
 
 Z is (CR a R b ) n , wherein n is 0, 1, or 2.  
 
     
     
         3 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein A, B, G, D, R a , R b , W, and Z are defined as in  claim 1 .  
     
     
         4 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R a , R b , and W are defined as in  claim 1 .  
     
     
         5 . A compound or salt according to  claim 4  wherein 
 R 1  is hydrogen, halogen, C 1 -C 2 alkyl or C 1 -C 2 alkoxy;  
 R a  is selected from hydrogen, halogen, C 1 -C 6  alkyl, C 1  C 6 alkoxy, haloalkyl, haloalkoxy, hydroxy C 1 -C 6 alkyl, mono- or di-(C 1 -C 6 )alkylamino, mono- or di-(C 1 -C 6 ) alkyl 3 amino(C 1 -C 6 )alkyl where each alkyl 3  may be substituted by mono- or di-(C 1 -C 6 )alkylamino, heterocycloalkyl(C 1 -C 6 )alkyl, heterocycloalkyl(C 1 -C 6 )alkylamino, and heterocycloalkyl which may be substituted by C 1 -C 6 alkyl;  
 R b  is selected from hydrogen, halogen, hydroxy, methyl, and ethyl, and  
 W is phenyl, pyridyl, thienyl, or pyrimidinyl, each of which is substituted with R d , R d ′, and R d ″, where R d , R d ′, and R d ″ are independently selected from hydrogen, halogen, hydroxy, haloalkyl, haloalkoxy di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkoxy, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, mono- or di-(C 1 -C 6 )alkylamino, C 1 -C 6  alkylamino (C 1 -C 6 )alkoxy, C 3 -C 7  cycloalkylamino(C 1 -C 6 )alkoxy, and heteroaryl(C 1 -C 6 )alkoxy.  
 
     
     
         6 . A compound or salt of  claim 5  wherein R d , R d ′, and R d  are independently hydrogen, fluorine or hydroxyl.  
     
     
         7 . A compound or salt according to  claim 5 , wherein W is phenyl carrying R d , R d ′, and R d ″ where one of R d , R d ′, and R d ″ is hydrogen and the other two are independently hydrogen, haloalkyl, haloalkoxy C 1 -C 6  alkyl, C 1 -C 6  alkoxy, mono- or di-(C 1 -C 6 )alkylamino, C 1 -C 6  alkylamino(C 1 -C 6 )alkoxy, C 3 -C 7  cycloalkylamino(C 1 -C 6 )alkoxy, or heteroaryl(C 1 -C 6 )alkoxy.  
     
     
         8 . A compound or salt of  claim 7  wherein R a  is hydrogen, hydroxy(C 1 -C 6 )alkyl, 4-(C 1 -C 6 )alkyl-[1,4]diazepan-1-yl(C 1 -C 6 )alkyl, 4-(C 1 -C 6 )alkyl-piperazin-1-yl(C 1 -C 6 )alkyl, mono- or di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl((C 1 -C 6 )alkyl)amino(C 1 -C 6 )alkyl, mono- or di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, or pyrrolidin-1-yl or piperidin-1-yl(C 1 -C 6 )alkylamino (C 1 -C 6 )alkyl.  
     
     
         9 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein G, D, E, R a , R b , W, and Z are defined as in  claim 1 .  
     
     
         10 . A compound or salt of  claim 7  wherein R a  is hydroxymethyl.  
     
     
         11 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R a , R b , W, and Z are defined as in  claim 1 .  
     
     
         12 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R a , R b , W, and Z are defined as in  claim 1 .  
     
     
         13 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R a , R b , and Z are defined as in  claim 1;  and 
 W is phenyl or thienyl, each of which is optionally mono- of disubstituted with groups independently selected from C 1 -C 6  alkyl, C 1 -C 6  alkoxy, halogen, hydroxy, haloalkyl, haloalkoxy, mono- or di-(C 1 -C 6 )alkylamino, C 1 -C 6  alkylamino(C 1 -C 6 )alkoxy, C 1 -C 6  alkoxy, C 3 -C 7  cycloalkylamino(C 1 -C 6 )alkoxy, and heteroaryl(C 1 -C 6 )alkoxy.  
 
     
     
         14 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R a , R b , and Z are defined as in  claim 1;  and 
 W is phenyl or thienyl substituted with R d , R d ′, and R d ″.  
 
     
     
         15 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R a , R b , and Z are defined as in  claim 1 , and  
 W is phenyl or thienyl each of which is substituted with R d , R d ′, and R d ″.  
 
     
     
         16 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R a , and R b , are defined as in  claim 1  and 
 W is phenyl, pyridyl, thienyl, or pyrimidinyl each of which is substituted with R d , R d ′, and R d ″ wherein 
 R d , R d ′, and R d ″ are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, haloalkyl, haloalkoxy, hydroxy, amino, and C 1 -C 6  alkyl substituted with 0-2 R 6 , C 1 -C 6  alkoxy substituted with 0-2 R 6 , —NH(C 1-6  alkyl) substituted with 0-2 R 6 , —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl) wherein each alkyl is independently substituted with 0-2 R 6 , —XR 7 , and Y;  
 X at each occurrence is independently selected from the group consisting of —CH 2 —, —CHR 8 —, —O—, —NH—, and —NR 8 —;  
 R 6  at each occurrence is independently selected from the group consisting of halogen, hydroxy, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), —NH—(C 1 -C 6  alkyl-Y), —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-Y), —NH—(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)), —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)), morpholinyl, pyrrolidinyl, piperidinyl, thiomorpholinyl, piperazinyl, homopiperazinyl, —S(O) m  (OC-C 6  alkyl), haloalkyl, haloalkoxy, —CO(C 1 -C 6  alkyl), —CONH(C 1 -C 6  alkyl), CON(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), —XR 7 , and Y; wherein 
 m is 0, 1, or 2;  
 
 R 7  and R 8  at each occurrence are independently C 1 -C 8  alkyl, wherein R 7  and R 8  are substituted with 0, 1, 2, 3, or 4 substituents selected from the group consisting of oxo, hydroxy, halogen, amino, cyano, nitro, haloalkyl, haloalkoxy, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl); and  
 Y at each occurrence is independently selected from 5- to 8-membered carbocycles or heterocycles, which are saturated, partiallyunsaturated, or aromatic and contain zero, one or two heteroatom(s) selected from N, O, and S, and which carbocycles or heterocycles may be further substituted with one or more substituents selected from halogen, oxo, hydroxy, amino, nitro, cyano, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, and mono- or di C 1 -C 6  alkylamino.  
 
 
     
     
         17 . A compound or salt according to  claim 4  wherein R b  is hydrogen; and W is phenyl or thienyl each of which is substituted with R d , R d ′, and R d ″ where R d , R d ′, and R d ″ are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, haloalkyl, haloalkoxy, hydroxy, amino, and C 1 -C 6  alkyl substituted with 0-2 R 6 , C 1 -C 6  alkoxy substituted with 0-2 R 6 , —NH(C 1-6  alkyl) substituted with 0-2 R 6 , —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl) wherein each alkyl is independently substituted with 0-2 R 6 , —XR 7 , and Y; 
 X at each occurrence is independently selected from the group consisting of —CH 2 —, —CHR 8 —, —O—, —NH—, and —NR 8 —;  
 R 6  at each occurrence is independently selected from the group consisting of halogen, hydroxy, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), —NH—(C 1 -C 6  alkyl-Y), —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-Y), —NH—(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)), —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)), morpholinyl, pyrrolidinyl, piperidinyl, thiomorpholinyl, piperazinyl, homopiperazinyl, —S(O) m (C 1 -C 6  alkyl), haloalkyl, haloalkoxy, —CO(C 1 -C 6  alkyl), —CONH(C 1 -C 6  alkyl), CON(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), —XR 7 , and Y; wherein 
 m is 0, 1, or 2;  
 
 R 7  and R 8  at each occurrence are independently C 1 -C 8  alkyl, wherein R 7  and R 8  are substituted with 0, 1, 2, 3, or 4 substituents selected from the group consisting of oxo, hydroxy, halogen, amino, cyano, nitro, haloalkyl, haloalkoxy, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl), and —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl); and  
 Y at each occurrence is independently selected from 5- to 8-membered carbocycles or heterocycles, which are saturated, partially unsaturated, or aromatic and contain zero, one or two heteroatom(s) selected from N, O, and S, and which carbocycles or heterocycles may be further substituted with one or more substituents selected from halogen, oxo, hydroxy, amino, nitro, cyano, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, and mono- or di C 1 -C 6  alkylamino.  
 
     
     
         18 . A compound or salt according to  claim 17  wherein R a  and R b  are hydrogen or R a  is hydroxymethyl and R b  is hydrogen.  
     
     
         19 . A compound according to  claim 1 , which selected from 
 1-[[2-(2-Fluoro-4-hydroxyphenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[6-Fluoro-2-(4-fluorophenyl)-4-quinolinyl]carbonyl]-pyrrolidine;    1-[[6-Fluoro-2-(3,4-difluorophenyl)-4-quinolinyl]carbonyl]-pyrrolidine;    1-[[2-(4-Fluorophenyl)-4-quinolinyl]carbonyl]pyrrolidine; and    1-[[2-(2,4-Difluorophenyl)-4-quinolinyl]carbonyl]pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         20 . A compound according to  claim 1 , which is selected from 1-[[2-(3-Chloro-4-fluorophenyl)-4-quinolinyl]carbonyl]pyrrolidine; 
 1-[[6-Fluoro-2-(3-thienyl)-4-quinolinyl]carbonyl]-pyrrolidine;    1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-(2-Fluorophenyl)-4-quinolinyl]carbonyl]-pyrrolidine;    1-[[(6-Fluoro-2-phenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-[3-(3-n-propylamino-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-(2,5-Difluorophenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-[3-(3-cyclopropylamino-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-(3-Hydroxyphenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[(6-Chloro-2-phenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-[4-(3-n-propylamino-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine; and    1-[[6-Chloro-2-(2-fluorophenyl)-4-quinolinyl]carbonyl]pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         21 . A compound according to  claim 1 , which is selected from 
 1-[[2-[3-(2-n-Propylamino-1-ethoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-[4-(3-Ethylamino-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-[4-(3-n-Butylamino-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-(3-Fluoro-4-hydroxyphenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-[3-(2-Methylamino-1-ethoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-(2-Fluoro-4-methoxyphenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-[3-(3-N-Pyrrolidinyl-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-(3-Methoxyphenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-[4-(3-i-propylamino-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine; and    1-[[2-[3-(2-Imdazolyl-1-ethoxy)phenyl]-4-quinolinyl]carbonyl]-pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         22 . A compound according to  claim 1 , which is selected from 
 1-[[2-(3-Fluoro-4-methoxyphenyl)-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-(2-Methylphenyl)-4-quinolinyl]carbonyl]-pyrrolidine;    1-[[2-[4-(3-piperidinylamino-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    1-[[2-(4-(3-Diethylamino-1-propoxy)phenyl]-4-quinolinyl]carbonyl]pyrrolidine;    (R)-1-[[6-Fluoro-2-(4-fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (R)-1-[[2-(4-Fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (R)-1-[(6-Chloro-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine; and    (R)-1-[[2-(3-Chloro-4-fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         23 . A compound according to  claim 1 , which is selected from 
 (R)-1-[[6-Fluoro-2-(3,4-difluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine;    (R)-1-[[2-(4-Methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (R)-1-[[6-Fluoro-2-(4-fluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[2-(3-Methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[(6-Fluoro-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[2-(2-Fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[2-(2-Methylphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[6-Fluoro-2-(2-fluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[6-Fluoro-2-(3-thienyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine; and    (R)-1-[[2-Phenyl-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         24 . A compound according to  claim 1 , which is selected from 
 (R)-1-[[2-(2-Fluoro-4-hydroxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[2-(2,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-([2-(2-Fluoro-4-ethoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[2-(2,6-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[6-Bromo-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[2-[2-Fluoro-4-(3-bromo-1-propoxy)phenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (R)-1-[[2-(2-Fluoro-4-methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (R)-1-[[2-(2,5-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (R)-1-[[6-Methoxy-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine;    (R)-1-[[6-Chloro-2-(2-fluoro-4-methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylamino-1-ethyl-1-methyl-aminomethyl)pyrrolidine; and    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-ethylpiperazinyl)methyl)pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         25 . A compound according to  claim 1 , which is selected from 
 (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylamino-1-ethyl-1-ethyl-aminomethyl)pyrrolidine;    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylaminoethyl)-aminomethyl)pyrrolidine;    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-dimethylamino-1-ethyl-1-methyl-aminomethyl)pyrrolidine;    (R)-1-[[2-(4-Fluorophenyl)-4-quinolinyl]carbonyl]-2-(2-dimethylaminoethyl)aminomethyl)pyrrolidine;    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-methylhomopiperazinyl)methyl)pyrrolidine;    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-methylpiperazinyl)methyl)pyrrolidine;    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-piperidinylethylaminomethyl)pyrrolidine;    (R)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-pyrrolidinylethylaminomethyl)pyrrolidine;    (R)-1-[(2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl pyrrolidine; and    1-[[2-(4-Fluorophenyl)-4-quinolinyl]carbonyl]-3-hydroxy-pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         26 . A compound according to  claim 1 , which is selected from 
 1-[(2-phenylthieno[3,2-b]pyridyl)carbonyl]-pyrrolidine;    (R)-1-[(2-phenylthieno[3,2-b]pyridyl)carbonyl]-2-hydroxymethyl-pyrrolidine; and    1-[(2-phenyl-1,6-naphthyridinyl)carbonyl]-pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         27 . A compound according to  claim 1 , which is selected from 
 (S)-1-[[6-Fluoro-2-(4-fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (S)-1-[[2-(4-Fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (S)-1-[(6-Chloro-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine; and    (S)-i-[[2-(3-Chloro-4-fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         28 . A compound according to  claim 1 , which is selected from 
 (S)-1-[[6-Fluoro-2-(3,4-difluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine;    (S)-1-[[2-(4-Methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (S)-1-[[6-Fluoro-2-(4-fluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[2-(3-Methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[(6-Fluoro-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[2-(2-Fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[(2-(2-Methylphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[(6-Fluoro-2-(2-fluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-([6-Fluoro-2-(3-thienyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine; and    (S)-1-[[2-Phenyl-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         29 . A compound according to  claim 1 , which is selected from 
 (-S)-1-[[2-(2-Fluoro-4-hydroxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[2-(2,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[2-(2-Fluoro-4-ethoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[2-(2,6-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[6-Bromo-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[2-[2-Fluoro-4-(3-bromo-1-propoxy)phenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (S)-1-[[2-(2-Fluoro-4-methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (S)-1-[[2-(2,5-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (S)-1-[[6-Methoxy-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine;    (S)-1-[[6-Chloro-2-(2-fluoro-4-methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylamino-1-ethyl-1-methyl-aminomethyl)pyrrolidine; and    (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-ethylpiperazinyl)methyl)pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         30 . A compound according to  claim 1 , which is selected from (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylamino-1-ethyl-1-ethyl-aminomethyl)pyrrolidine; 
 (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylaminoethyl)-aminomethyl)pyrrolidine;    (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-dimethylamino-1-ethyl-1-methyl-aminomethyl)pyrrolidine;    (S)-1-[[2-(4-Fluorophenyl)-4-quinolinyl]carbonyl]-2-(2-dimethylaminoethyl)aminomethyl)pyrrolidine;    (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-methylhomopiperazinyl)methyl)pyrrolidine;    (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-methylpiperazinyl)methyl)pyrrolidine;    (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-piperidinylethylaminomethyl)pyrrolidine;    (S)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-pyrrolidinylethylaminomethyl)pyrrolidine;    (S)-1-[(2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl pyrrolidine; and    (S)-1-[(2-phenylthieno[3,2-b]pyridyl)carbonyl]-2-hydroxymethyl-pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         31 . A compound according to  claim 1 , which is selected from 
 (±)-1-[[6-Fluoro-2-(4-fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (±)-1-[[2-(4-Fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (±)-1-[(6-Chloro-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine; and    (±)-1-[[2-(3-Chloro-4-fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         32 . A compound according to  claim 1 , which is selected from 
 (±)-1-[[6-Fluoro-2-(3,4-difluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine;    (±)-1-[[2-(4-Methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (±)-1-[[6-Fluoro-2-(4-fluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[2-(3-Methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[(6-Fluoro-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[2-(2-Fluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[2-(2-Methylphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[6-Fluoro-2-(2-fluorophenyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[6-Fluoro-2-(3-thienyl)-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine; and    (±)-1-[[2-Phenyl-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         33 . A compound according to  claim 1 , which is selected from 
 (±)-1-[[2-(2-Fluoro-4-hydroxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[2-(2,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[(2-(2-Fluoro-4-ethoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[2-(2,6-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[6-Bromo-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[2-[2-Fluoro-4-(3-bromo-1-propoxy)phenyl)-4-quinolinyl]carbonyl]-2-hydroxymethyl-pyrrolidine;    (±)-1-[[2-(2-Fluoro-4-methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (±)-1-[[2-(2,5-Difluorophenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (±)-1-[[6-Methoxy-2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethylpyrrolidine;    (±)-1-[[6-Chloro-2-(2-fluoro-4-methoxyphenyl)-4-quinolinyl]carbonyl]-2-hydroxymethylpyrrolidine;    (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylamino-1-ethyl-1-methyl-aminomethyl)pyrrolidine; and    (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-ethylpiperazinyl)methyl)pyrrolidine; and the pharmaceutically acceptable salts thereof.    
     
     
         34 . A compound according to  claim 1 , which is selected from (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylamino-1-ethyl-1-ethyl-aminomethyl)pyrrolidine; 
 (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-diethylaminoethyl)-aminomethyl)pyrrolidine;  
 (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(2-dimethylamino-1-ethyl-1-methyl-aminomethyl)pyrrolidine;  
 (±)-1-[[2-(4-Fluorophenyl)-4-quinolinyl]carbonyl]-2-(2-dimethylaminoethyl)aminomethyl)pyrrolidine;  
 (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-methylhomopiperazinyl)methyl)pyrrolidine;  
 (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-methylpiperazinyl)methyl)pyrrolidine;  
 (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-piperidinylethylaminomethyl)pyrrolidine;  
 (±)-1-[[2-(3,4-Difluorophenyl)-4-quinolinyl]carbonyl]-2-(N-pyrrolidinylethylaminomethyl)pyrrolidine;  
 (±)-1-[(2-phenyl-4-quinolinyl)carbonyl]-2-hydroxymethyl pyrrolidine; and  
 (±)-1-[(2-phenylthieno[3,2-b]pyridyl)carbonyl]-2-hydroxymethyl-pyrrolidine; and the pharmaceutically acceptable salts thereof.  
 
     
     
         35 . A compound according to  claim 1  for use in therapeutic treatment of a disease or disorder associated with pathogenic agonism, inverse agonism or antagonism of the GABA A  receptor.  
     
     
         36 . A pharmaceutical composition comprising a compound or salt according to  claim 1  combined with at least one pharmaceutically acceptable carrier or excipient.  
     
     
         37 . A method for the treatment of a disease or disorder associated with pathogenic agonism, inverse agonism or antagonism of the GABA A  receptor, said method comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a compound or salt of  claim 1 .  
     
     
         38 . A method according to  claim 32  wherein the disease or disorder associated with pathogenic agonism, inverse agonism or antagonism of the GABA A  receptor is anxiety, depression, a sleep disorder, or cognitive impairment.  
     
     
         39 . The use of a compound or salt according to  claim 1  for the manufacture of a medicament for the treatment of a disease or disorder associated with pathogenic agonism, inverse agonism or antagonism of the GABA A  receptor.  
     
     
         40 . The use of a compound or salt according to  claim 1  for the manufacture of a medicament for the treatment of anxiety, depression, sleep disorders, or cognitive impairment.  
     
     
         41 . A method for localizing GABA A  receptors in a tissue sample comprising: 
 contacting with the sample a detectably-labeled compound or salt of  claim 1  under conditions that permit binding of the compound to GABA A  receptors, washing the sample to remove unbound compound, and detecting the bound compound.    
     
     
         42 . A method of inhibiting the binding of a benzodiazepine compound to a GABA A  receptor, said method comprising contacting a compound or salt of  claim 1  with cells expressing such a receptor in the presence of the benzodiazepine, wherein the compound is present at a concentration sufficient to inhibit the binding a benzodiazepine compound to a GABA A  receptor in vitro.  
     
     
         43 . A method for altering the signal-transducing activity of GABA A  receptors, said method comprising exposing cells expressing such receptors to a compound or salt according to  claim 1  at a concentration sufficient to inhibit RO15-1788 binding to cells expressing a cloned human GABA A  receptor in vitro.  
     
     
         44 . A packaged pharmaceutical composition comprising the pharmaceutical composition of  claim 30  in a container and instructions for using the composition to treat a patient suffering from a disorder responsive to agonism, inverse agonism or antagonism of the GABA A  receptor.  
     
     
         45 . The packaged pharmaceutical composition of  claim 39 , wherein said patient is suffering from anxiety, depression, a sleep disorder, or cognitive impairment.  
     
     
         46 . A compound or salt according to  claim 1  wherein in a assay of GABA A  receptor binding the compound exhibits an IC 50  of 1 micromolar or less.  
     
     
         47 . A compound or salt according to  claim 1  wherein in a assay of GABA A  receptor binding the compound exhibits an IC50 of 100 nanomolar or less.  
     
     
         48 . A compound or salt according to  claim 1  wherein in a assay of GABA A  receptor binding the compound exhibits an IC 50  of 10 nanomolar or less.  
     
     
         49 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R a  and W are defined as in  claim 1;  and 
 R 1  is selected from the group consisting of hydrogen, halogen, hydroxy, C 1 -C 6  alkoxy, and C 1 -C 6  alkyl.  
 
     
     
         50 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein W is defined as in  claim 1;  
 R 1  is selected from the group consisting of hydrogen, halogen, hydroxy, C 1 -C 6  alkoxy, and C 1 -C 6  alkyl;  
 R a  is selected from the group consisting of hydrogen, —XR 7 , and C 1 -C 6  alkyl, wherein the C 1 -C 6  alkyl is optionally substituted with 0, 1, or 2 R 6 ; 
 R 6  is selected from the group consisting of —NH—(C 1 -C 6  alkyl-Y), —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-Y), —NH—(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)), and —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl));  
 X is selected from the group consisting of —CH 2 —, —CHR 8 —, —C(O)—, —C(O)O—, —C(O)NH—, —C(O)N(C 1 -C 6  alkyl)-, and —C(O)N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)-;  
 R 7  and R 8  at each occurrence are independently C 1 -C 6  alkyl optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of hydroxy, amino, —NH(C 1 -C 8  alkyl), —NH(C 1 -C 8  alkyl)(C 1 -C 8  alkyl); and  
 Y is selected from 5- to 8-membered carbocycles or heterocycles, which are saturated, partiallyunsaturated, or aromatic and contain zero, one or two heteroatoms selected from N, O, and S, which carbocycles or heterocycles may be further substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, hydroxy, amino, nitro, cyano, alkyl, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl) —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), and —S(O) a (C 1 -C 6  alkyl); wherein 
 a is 0, 1, or 2.  
 
 
 
     
     
         51 . A compound or salt according to  claim 1  of the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is selected from the group consisting of hydrogen, halogen, hydroxy, C 1 -C 6  alkoxy, and C 1 -C 6  alkyl;  
 R a  is selected from the group consisting of hydrogen, —XR 7 , and C 1 -C 6  alkyl, wherein the C 1 -C 6  alkyl is optionally substituted with 0, 1, or 2 R 6 ; 
 R 6  is selected from the group consisting of —NH—(C 1 -C 6  alkyl-Y), —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-Y), —NH—(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)), and —N(C 1 -C 6  alkyl)-(C 1 -C 6  alkyl-N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl));  
 
 X is selected from the group consisting of —CH 2 —, —CHR 8 —, —C(O)—, —C(O)O—, —C(O)NH—, —C(O)N(C 1 -C 6  alkyl)-, and —C(O)N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl)-; and  
 R 7  and R 8  at each occurrence are independently C 1 -C 6  alkyl optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of hydroxy, amino, —NH(C 1 -C 8  alkyl), —NH(C 1 -C 8  alkyl)(C 1 -C 8  alkyl);  
 W is thienyl or phenyl, wherein each is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, hydroxy, C 1 -C 6  alkoxy, optionally substituted with amino, NH(C 1 -C 6  alkyl), NH(C 3 -C 6  cycloalkyl), halogen, and Y; and 
 Y is selected from 5- to 8-membered carbocycles or heterocycles, which are saturated, partially unsaturated, or aromatic and contain zero, one or two heteroatoms selected from N, O, and S, which carbocycles or heterocycles may be further substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, hydroxy, amino, nitro, cyano, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)(C 1 -C 6  alkyl), and —S(O) a (C 1 -C 6  alkyl); wherein 
 a is 0, 1, or 2.  
 
 
 
     
     
         52 . A compound or salt of  claim 7  wherein R a  is hydrogen, hydroxymethyl, [(2-diethylamino-ethyl)-methyl-amino]methyl, or [(2-Diethylamino-ethyl)-methyl-amino]methyl.  
     
     
         53 . A compound or salt according to  claim 5 , wherein W is phenyl carrying R d , R d ′, and R d ″ where one of R d , R d ′, and R d ″ is hydrogen and the other two are independently hydrogen, halogen, hydroxy, C 1 -C 6  alkylamino(C 1 -C 6 )alkoxy, C 1 -C 6  or alkoxy.  
     
     
         54 . A method for preparing a compound of  claim 1.