Derivatives of quinoline as alpha-2 antagonists

Abstract

A compound of formula I, wherein A, Ra, Rb, R 1 to R 5 , m and t are as defined as disclosed, or a pharmaceutically acceptable salt or ester thereof, useful as an alpha-2 antagonist. The compounds I can be used for the treatment of diseases or conditions where alpha-2 antagonists are indicated to be effective.

We claim:  
     
         1 . A method for the treatment of a disease or condition where an antagonist of alpha-2 adrenoceptors is indicated to be useful, which comprises administering to a mammal in need of the treatment an effective amount of at least one compound of formula I,  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein,  
         R 1  is H or (C 1 -C 6 )alkyl;  
         each R 2  is independently OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-S— or hydroxy(C 1 -C 6 )alkyl;  
         A is a benzene ring or (C 5 -C 7 )cycloalkyl;  
         when A is a benzene ring each R 3  is independently OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, halo-(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-CO—, mono- or di(C 1 -C 6 )-alkylcarbamoyl, (C 1 -C 6 )alkyl-S—, hydroxy(C 1 -C 6 )alkyl or NH 2 —CO—;  
         when A is (C 5 -C 7 )cycloalkyl each R 3  is independently OH, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mono- or di(C 1 -C 6 )alkylamino or hydroxy(C 1 -C 6 )alkyl;  
         R 4  and R 5  form, together with the N-atom to which they are attached,  
         
           
             
             
                 
                 
             
           
         
         wherein X is O or ═NR 6 ; R 6  is H, OH, NH 2 , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, CN—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-CO—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-CO—, NH 2 —CO—, mono- or di(C 1 -C 6 )alkylcarbamoyl, hydroxy(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, phenyl, naphthyl or benzyl, wherein the said phenyl, naphthyl or benzyl is optionally substituted with one to three substituent(s) each independently being OH, halogen, NO 2 , NH 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mono- or di(C 1 -C 6 )alkylamino or halo-(C 1 -C 6 )alkyl;  
         or R 4  and R 5  form, together with the N-atom to which they are attached,  
         
           
             
             
                 
                 
             
           
         
         wherein n=1 or 2; R 6  is as defined above; and r=0 to 3;  
         or R 4  and R 5  form, together with the N-atom to which they are attached, 1-imidazolyl, 1-imidazolinyl or 1-triazolyl, each of which can optionally be substituted with one to three substituent(s) R 7  each independently being (C 1 -C 6 )alkyl or NH 2 ;  
         or one of R 4  and R 5  is —SO 2 R 8  and the other of R 4  and R 5  is H or (C 1 -C 6 )alkyl; R 8  is (C 1 -C 6 )alkyl, phenyl, naphthyl or benzyl, wherein the said phenyl, naphthyl or benzyl is optionally substituted with one to three substituent(s) R 9  each independently being OH, halogen, NO 2 , NH 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or mono- or di(C 1 -C 6 )alkylamino;  
         Ra and Rb are independently H, OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-S— or CN;  
         or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed benzene ring optionally substituted with one to three substituent(s) R′ 3  each independently being OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, halo-(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-CO—, mono- or di(C 1 -C 6 )-alkylcarbamoyl or (C 1 -C 6 )alkyl-S—, hydroxy(C 1 -C 6 )alkyl or NH 2 —CO—;  
         or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed five to seven membered carbocyclic ring optionally substituted with one to four substituent(s) R 10  each independently being OH, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mono- or di(C 1 -C 6 )alkylamino or hydroxy(C 1 -C 6 )alkyl;  
         or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed bicyclo[2.2.1]-heptane ring optionally substituted with one to four substituent(s) each independently being OH, halogen, (C 1 -C 6 )alkyl or (C 1 -C 6 )alkoxy;  
         or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed five or six membered heterocyclic ring with one ring heteroatom ═NR 11 , which heterocyclic ring is optionally substituted with one to three substituent(s) R 10  as defined above; R 11  is H or (C 1 -C 6 )alkyl, or R 11  is phenyl optionally substituted with one to three substituents R 12  each independently being OH, halogen, NO 2 , NH 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or mono- or di(C 1 -C 6 )alkylamino;  
         m is 0 to 3; and  
         t is 0 to 3.  
       
     
     
         2 . The method of  claim 1 , which comprises administering at least one compound of formula IA  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 10 , m and t are as defined in  claim 1;  i is 1 to 3; and j is 0 to 4.  
       
     
     
         3 . The method of  claim 1 , which comprises administering at least one compound of formula IB  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein A, R 1 , R 2 , R 3 , R 4 , R 5 , m and t are as defined in  claim 1;  and Ra and Rb are independently H, OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-S— or CN; or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed five to seven membered carbocyclic ring optionally substituted with one to three substituent(s) R 10 ; each independently being OH, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mono- or di(C 1 -C 6 )alkylamino or hydroxy(C 1 -C 6 )alkyl.  
       
     
     
         4 . The method of  claim 1 , which comprises administering at least one compound of formula IC  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 10 , R 11 , m and t are as defined in  claim 1;  i is 1 or 2; and j is 0 to 3.  
       
     
     
         5 . The method of  claim 1 , which comprises administering at least one compound of formula ID  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein R 1 , R 2 , R 3 , R′ 3 , R 4 , R 5 , m and t are as defined in  claim 1;  and p is 0 to 3.  
       
     
     
         6 . The method according to  claim 5 , wherein m is 1 and R 3  is (C 1 -C 6 )alkoxy.  
     
     
         7 . The method according to  claim 1 , wherein R 4  and R 5  form, together with the N-atom to which they are attached,  
       
         
           
           
               
               
           
         
       
       wherein X is as defined in  claim 1 .  
     
     
         8 . The method according to  claim 7 , wherein X is ═NR 6 .  
     
     
         9 . The method according to  claim 8 , wherein R 6  is (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, (C 3 -C 6 )cycloalkyl or hydroxy(C 1 -C 6 )alkyl.  
     
     
         10 . The method according to  claim 9 , wherein R 6  is (C 1 -C 6 )alkyl.  
     
     
         11 . The method according to  claim 1 , wherein, when one of R 4  and R 5  is —SO 2 R 8  and the other of R 4  and R 5  is H or (C 1 -C 6 )alkyl; R 8  is not (C 1 -C 6 )alkyl.  
     
     
         12 . The method according to  claim 5 , wherein, when one of R 4  and R 5  is —SO 2 R 8  and the other of R 4  and R 5  is H or (C 1 -C 6 )alkyl; R 8  is not (C 1 -C 6 )alkyl.  
     
     
         13 . The method according to  claim 1 , which comprises treating a disorder of the central nervous system, male sexual impotence, orthostatic hypotension, non-insulin dependent diabetes, or obesity.  
     
     
         14 . The method according to  claim 1 , which comprises a treatment to reverse alpha-2 agonistic effects.  
     
     
         15 . The method according to  claim 13 , which comprises treating a disorder of the central nervous system.  
     
     
         16 . The method according to  claim 15 , wherein the disorder of the central nervous system is depression, anxiety, post-traumatic stress disorder, schizophrenia, Parkinson's disease, or another movement disorder.  
     
     
         17 . A compound of formula II,  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein,  
         R 1  is H or (C 1 -C 6 )alkyl;  
         each R 2  is independently OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-S— or hydroxy(C 1 -C 6 )alkyl;  
         A is a benzene ring or (C 5 -C 7 )cycloalkyl;  
         when A is a benzene ring each R 3  is independently OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, halo-(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-CO—, mono- or di(C 1 -C 6 )-alkylcarbamoyl, (C 1 -C 6 )alkyl-S—, hydroxy(C 1 -C 6 )alkyl or NH 2 —CO—;  
         when A is (C 5 -C 7 )cycloalkyl each R 3  is independently OH, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mono- or di(C 1 -C 6 )alkylamino or hydroxy(C 1 -C 6 )alkyl;  
         R 4  and R 5  form, together with the N-atom to which they are attached,  
         
           
             
             
                 
                 
             
           
         
         wherein X is O or ═NR 6 ; R 6  is H, OH, NH 2 , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, CN—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-CO—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-CO—, NH 2 —C—, mono- or di(C 1 -C 6 )alkylcarbamoyl, hydroxy(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl or benzyl, wherein the said benzyl is optionally substituted with one to three substituent(s) each independently being OH, halogen, NO 2 , NH 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mono- or di(C 1 -C 6 )alkylamino or halo-(C 1 -C 6 )alkyl;  
         or R 4  and R 5  form, together with the N-atom to which they are attached,  
         
           
             
             
                 
                 
             
           
         
         wherein n=1 or 2; R 6  is as defined above; and r=0 to 3;  
         or R 4  and R 5  form, together with the N-atom to which they are attached, 1-imidazolyl, 1-imidazolinyl or 1-triazolyl, each of which can optionally be substituted with one to three substituent(s) R 7  each independently being (C 1 -C 6 )alkyl or NH 2 ;  
         Ra and Rb are independently H, OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-S— or CN;  
         or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed benzene ring optionally substituted with one to three substituent(s) R′ 3  each independently being OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, halo-(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-CO—, mono- or di(C 1 -C 6 )-alkylcarbamoyl or (C 1 -C 6 )alkyl-S—, hydroxy(C 1 -C 6 )alkyl or NH 2 —CO—;  
         or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed five to seven membered carbocyclic ring optionally substituted with one to four substituent(s) R 10  each independently being OH, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mono- or di(C 1 -C 6 )alkylamino or hydroxy(C 1 -C 6 )alkyl;  
         or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed bicyclo[2.2.1]-heptane ring optionally substituted with one to four substituent(s) each independently being OH, halogen, (C 1 -C 6 )alkyl or (C 1 -C 6 )alkoxy;  
         or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed five or six membered heterocyclic ring with one ring heteroatom ═NR 11 , which heterocyclic ring is optionally substituted with one to three substituent(s) R 10  as defined above; R 11  is H or (C 1 -C 6 )alkyl, or R 11  is phenyl optionally substituted with one to three substituents R 12  each independently being OH, halogen, NO 2 , NH 2 , (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or mono- or di(C 1 -C 6 )alkylamino;  
         m is 0 to 3; and  
         t is 0 to 3,  
         with the provisos, that 
 a) when A is a benzene ring, m is 0 or 1, t is 0, R 1  is H, R 3  is Cl or NO 2 , and Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed benzene ring, and X is NR 6 , then R 6  is not H, —CH 3 , —CH 2 CH 3 , —COCH 3 , or —CO—NH 2 ;  
 b) when A is a benzene ring, then Ra and Rb are not at the same time H;  
 c) when A is a benzene ring, m is 1, t is 0, R 1  is H, and Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed benzene ring, which is optionally substituted with Br, and X is O, then R 3  is not NO 2  or —OCH 3 ;  
 d) when A is a benzene ring, m is 0, t is 0, R 1  is H, and Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed nonsubstituted benzene ring, then X is not O;  
 e) the compound is not 4-[4-[(7-Chloro-2-methyl-4-quinolinyl)amino]phenyl]-1-diethylcarbamoylpiperazine, 4-[4-[(6-Chloro-2-methoxy-9-acridinyl)amino]phenyl]-1-diethylcarbamoylpiperazine, 6-amino-4-[[3-chloro-4-(1H-imidazol-1-yl)phenyl]amino]-7-metoxy-3-quinolinecarbonitrile or 4-[[3-chloro-4-(1H-imidazol-1-yl)phenyl]amino]-7-methoxy-6-nitro-3-quinolinecarbonitrile.  
 
       
     
     
         18 . A compound according to  claim 17 , which is a compound of formula IIA,  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 10 , m and t are as defined in  claim 17;  i is 1 to 3; and j is 0 to 4.  
       
     
     
         19 . A compound according to  claim 18 , wherein i is 2, j is 0 or 1 and R 10  is (C 1 -C 3 )alkyl, wherein the (C 1 -C 3 )alkyl includes both straight and branched chain radicals of up to 3 carbon atoms.  
     
     
         20 . A compound according to  claim 18 , wherein m is 0 or 1 and R 3  is (C 1 -C 3 )alkyl or halogen, wherein the (C 1 -C 3 )alkyl includes both straight and branched chain radicals of up to 3 carbon atoms.  
     
     
         21 . A compound according to  claim 18 , wherein the compound is [4-(4-Methylpiperazin-1-yl)phenyl]-(1,2,3,4-tetrahydroacridin-9-yl)amine, 2-{4-[4-(1,2,3,4-Tetrahydroacridin-9-yl)aminophenyl]piperazin-1-yl}ethanol, [4-(4-Methylpiperazin-1-yl)phenyl]-(2-methyl-1,2,3,4-tetrahydro-acridin-9-yl)amine, (8-Fluoro-1,2,3,4-tetrahydroacridin-9-yl)-[4-(4-methylpiperazin-1-yl)phenyl]amine, [4-(4-Methylpiperazin-1-yl)phenyl]-(2,7-dimethyl-1,2,3,4-tetrahydroacridin-9-yl)amine, [4-(4-Methylpiperazin-1-yl)phenyl]-(7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-yl)amine or [4-(4-Methylpiperazin-1-yl)phenyl]-(1,1,3,3-tetramethyl-1,2,3,4-tetrahydroacridin-9-yl)amine.  
     
     
         22 . A compound according to  claim 17 , which is a compound of formula IIB,  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein A, R 1 , R 2 , R 3 , R 4 , R 5 , m and t are as defined in  claim 17;  and  
         Ra and Rb are independently H, OH, halogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, NO 2 , NH 2 , mono- or di(C 1 -C 6 )alkylamino, (C 1 -C 6 )alkyl-S— or CN; or Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed five to seven membered carbocyclic ring optionally substituted with one to three substituent(s) R 10 ; each independently being OH, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, mono- or di(C 1 -C 6 )alkylamino or hydroxy(C 1 -C 6 )alkyl.  
       
     
     
         23 . A compound according to  claim 22 , wherein A is a benzene ring.  
     
     
         24 . A compound according to  claim 22 , wherein m is 0 or 1.  
     
     
         25 . A compound according to  claim 22 , wherein R 3  is (C 1 -C 6 )alkyl or (C 1 -C 6 )alkoxy.  
     
     
         26 . A compound according to  claim 22 , wherein Ra and Rb are independently H or (C 1 -C 3 )alkyl, wherein the (C 1 -C 3 )alkyl includes both straight and branched chain radicals of up to 3 carbon atoms.  
     
     
         27 . A compound according to  claim 22 , wherein A is a six membered carbocyclic ring and Ra and Rb form, together with the carbon ring atoms to which they are attached, a condensed five to seven membered carbocyclic ring, wherein the carbocyclic ring can optionally be substituted with one to three substituent(s) each independently being OH, halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or hydroxy(C 1 -C 6 )alkyl.  
     
     
         28 . A compound according to  claim 22 , wherein the compound is (3-Ethyl-2,8-dimethylquinolin-4-yl)-[4-(4-methylpiperizin-1-yl)phenyl]amine, (2-Methylquinolin-4-yl)-[4-(4-methylpiperazin-1-yl)phenyl]amine, (3-Ethyl-2,6-dimethylquinolin-4-yl)-[4-(4-methylpiperazin-1-yl)phenyl]amine, (3-Ethyl-6-methoxy-2-methylquinolin-4-yl)-[4-(4-methylpiperazin-1-yl)phenyl]amine, (3-Ethyl-2-methylquinolin-4-yl)-[4-(4-methylpiperazin-1-yl)phenyl]amine, 4-[4-(4-Methylpiperazin-1-yl)phenylamino]quinoline-3-carbonitrile, 3-Isopropyl-2-methylquinolin-4-yl)-[4-(4-methylpiperazin-1-yl)phenyl]amine, (2,3-Dimethylquinolin-4-yl)-[4-(4-methylpiperazin-1-yl)phenyl]amine, [4-(4-Methylpiperazin-1-yl)phenyl]-(1,2,3,4,5,6,7,8-octahydroacridin-9-yl)amine or (3-Ethyl-2-methylquinolin-4-yl)-methyl-[4-(4-methylpiperazin-1-yl)phenyl]amine.  
     
     
         29 . A compound according to  claim 17 , which is a compound of formula IIC,  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 10 , R 11 , m and t are as defined in  claim 17;  i is 1 or 2; and j is 0 to 3.  
       
     
     
         30 . A compound according to  claim 17 , which is a compound of formula IID,  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or ester thereof,  
         wherein R 1 , R 2 , R 3 , R′ 3 , R 4 , R 5 , m and t are as defined in  claim 17;  and p is 0 to 3.  
       
     
     
         31 . A compound according to  claim 30 , wherein m is 1 and R 3  is (C 1 -C 6 )alkoxy.  
     
     
         32 . A compound of according to  claim 30 , wherein the compound is 2-{4-[4-(Acridin-9-yl)aminophenyl]piperazin-1-yl}-ethanol, (4-Methoxyacridin-9-yl)-[4-(4-methylpiperazin-1-yl)-phenyl]amine, Acridin-9-yl-[4-(piperidin-1-yl)phenyl]amine, Acridin-9-yl-[4-(4-benzylpiperazin-1-yl)phenyl]amine, Acridin-9-yl-[4-(4-methylpiperidin-1-yl)phenyl]amine, Acridin-9-yl-[4-(3-hydroxymethylpiperidin-1-yl)-phenyl]amine, Acridin-9-yl-[4-pyrrolidin-1-yl)phenyl]amine, Acridin-9-yl-[4-(4-cyclopropylpiperazin-1-yl)phenyl]amine, Acridin-9-yl-[4-(4-isopropylpiperazine-1-yl)phenyl]amine, (Acridin-9-yl)-methyl-[4-(4-methylpiperazin-1-yl)phenyl]amine or Acridin-9-yl-[2,5-diethoxy-4-(morpholin-4-yl)phenyl]amine.  
     
     
         33 . A compound according to  claim 17 , wherein R 4  and R 5  form, together with the N-atom to which they are attached,  
       
         
           
           
               
               
           
         
       
       wherein R 6  is (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, (C 3 -C 6 )cycloalkyl or hydroxy(C 1 -C 6 )alkyl.  
     
     
         34 . A compound according to  claim 33 , wherein R 6  is (C 1 -C 6 )alkyl.  
     
     
         35 . A pharmaceutical composition comprising at least one compound according to  claim 17  and a pharmaceutically acceptable diluent, carrier and/or excipient.  
     
     
         36 . A method for the treatment of a disease or condition where an antagonist of alpha-2 adrenoceptors is indicated to be useful, which comprises administering to a mammal in need of the treatment an effective amount of at least one compound according to  claim 17 .  
     
     
         37 . The method according to  claim 36 , which comprises treating a disorder of the central nervous system, male sexual impotence, orthostatic hypotension, non-insulin dependent diabetes, or obesity.  
     
     
         38 . The method according to  claim 36 , which comprises a treatment to reverse alpha-2 agonistic effects.  
     
     
         39 . The method according to  claim 37 , which comprises treating a disorder of the central nervous system.  
     
     
         40 . The method according to  claim 39 , wherein the disorder of the central nervous system is depression, anxiety, post-traumatic stress disorder, schizophrenia, Parkinson's disease, or another movement disorder.