US2006199828A1PendingUtilityA1

Pyrazine-2-carboxyamide derivatives

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Assignee: JAESCHKE GEORGPriority: Mar 4, 2005Filed: Feb 28, 2006Published: Sep 7, 2006
Est. expiryMar 4, 2025(expired)· nominal 20-yr term from priority
Inventors:Georg JaeschkeSabine KolczewskiRichard Hugh Philip PorterEric Vieira
A61P 3/10A61P 9/10A61P 43/00A61P 27/02A61P 25/34A61P 25/16A61P 3/04A61P 25/24A61P 25/32A61P 3/00A61P 25/00A61P 25/28A61P 29/00A61P 25/06A61P 25/22A61P 25/18A61P 25/14A61P 25/08C07D 401/14C07D 417/02A61P 1/08C07D 409/02C07D 417/14C07D 417/12C07D 403/14A61P 13/02A61P 17/02A61P 19/06C07D 403/02A61P 1/00C07D 241/26A61P 19/08A61P 21/00C07D 403/12C07D 401/12A61K 31/4965
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Claims

Abstract

The present invention is concerned with novel pyrazine 2-carboxyamide derivatives of formula (I) wherein R 1 , R 2 and R 3 are as defined in the specification. These compounds are useful for the treatment of CNS disorders.

Claims

exact text as granted — not AI-modified
1 . A compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is a 5- or 6-membered ring of formula (II) or (III):  
                     
 R 2  is H, C 1 -C 7 -alkyl, C 3 -C 6 -cycloalkyl, or —(CH 2 ) m —R a ;  
 R 3  is H, aryl, or heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl;  
 
 R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e ;  
 R 5  is C 1 -C 7 -alkyl, C 1 -C 7 -alkyl-C 3 -C 6 -cycloalkyl, —(CH 2 ) n —O—R f , C 3 -C 8 -alkenyl-O—R f , —(CH 2 ) n —NR g R h , —C 2 -C 6 -alkenyl-NR g R h , or —(CH 2 ) n —R e ;  
 R a  is —O—C 1 -C 7 -alkyl or —OH;  
 R b  is C 1 -C 7 -alkyl, NH 2 , or —O—C 1 -C 7 -alkyl;  
 R c  is —OH, NH 2 , or NH—(CO)—O—C 1 -C 7 -alkyl;  
 R d  is C 1 -C 7 -alkyl, —NH 2 , —NH—C 1 -C 7 -alkyl, or —N-di(C 1 -C 7 -alkyl);  
 R e  is —OH, —CH 2 F, —CHF 2 , —CF 3 , or —O—(CO)—C 1 -C 7 -alkyl;  
 R f  is C 1 -C 7 -alkyl, C 3 -C 8 -alkenyl, C 3 -C 6 -cycloalkyl, phenyl, benzyl, or —(CO)—R′;  
 R g  and R h  are each independently H, C 1 -C 7 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 8 -alkenyl, phenyl, benzyl, or —(CO)—R′ or R g  and R h , together with the nitrogen atom to which they are attached, form a 5- to 7-membered heterocyclic or heteroaryl ring optionally substituted with 1 or 2OH;  
 R′ is NH 2 , —NH—C 1 -C 7 -alkyl, C 1 -C 7 -alkyl, or C 1 -C 7 -alkoxy;  
 m is 1 to 4; and  
 n is 2 to 6;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         2 . The compound of  claim 1:   
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is a 5- or 6-membered ring of formula (II) or (III):  
                     
 R 2  is H, C 1 -C 7 -alkyl, C 3 -C 6 -cycloalkyl, or —(CH 2 ) m —R a ;  
 R 3  is aryl or heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl;  
 
 R 4  is —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e ;  
 R 5  is C 1 -C 7 -alkyl, C 1 -C 7 -alkyl-C 3 -C 6 -cycloalkyl, —(CH 2 ) n —O—R f , C 3 -C 8 -alkenyl-O—R f , —(CH 2 ) n —NR g R h , —C 2 -C 6 -alkenyl-NR g R h , or —(CH 2 ) n —R e ;  
 R a  is —O—C 1 -C 7 -alkyl or —OH;  
 R b  is C 1 -C 7 -alkyl, NH 2 , or —O—C 1 -C 7 -alkyl;  
 R c  is —OH, NH 2 , or NH—(CO)—O—C 1 -C 7 -alkyl;  
 R d  is C 1 -C 7 -alkyl, —NH 2 , —NH—C 1 -C 7 -alkyl, or —N-di(C 1 -C 7 -alkyl);  
 R e  is —OH, —CH 2 F, —CHF 2 , —CF 3 , or —O—(CO)—C 1 -C 7 -alkyl;  
 R f  is C 1 -C 7 -alkyl, C 3 -C 8 -alkenyl, C 3 -C 6 -cycloalkyl, phenyl, benzyl, or —(CO)—R′;  
 R g  and R h  are each independently H, C 1 -C 7 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 8 -alkenyl, phenyl, benzyl, or —(CO)—R′ or R g  and R h , together with the nitrogen atom to which they are attached, form a 5- to 7-membered heterocyclic or heteroaryl ring optionally substituted with 1 or 2OH;  
 R′ is NH 2 , —NH—C 1 -C 7 -alkyl, C 1 -C 7 -alkyl, or C 1 -C 7 -alkoxy;  
 m is 1 to 4; and  
 n is 2 to 6;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         3 . The compound of  claim 1  having formula (Ia)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         4 . The compound of  claim 3 , wherein 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         5 . The compound of  claim 4 , which is 6-Methyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide hydrochloride.  
     
     
         6 . The compound of  claim 1  having formula (Ib)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         7 . The compound of  claim 6 , wherein 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         8 . The compound of  claim 7 , which is 6-Methyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid (2-methyl-thiazol-4-yl)-amide hydrochloride.  
     
     
         9 . The compound of  claim 1  having formula (Ic)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         10 . The compound of  claim 9 , wherein 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , (CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         11 . The compound of  claim 10 , selected from the group consisting of: 
 3-(3-Fluoro-phenylamino)-pyrazine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;    3-(Pyridin-3-ylamino)-pyrazine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide dihydrochloride;    3-(Pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide;    6-Methyl-3-(pyridin-3-ylamino)-pyrazine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide hydrochloride; and    6-Methyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid (4-methyl-thiazol-2-yl)-amide.    
     
     
         12 . The compound of  claim 1  having formula (Id)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         13 . The compound of  claim 12 , wherein: 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 5  is C 1 -C 7 -alkyl, C 1 -C 7 -alkyl-C 3 -C 6 -cycloalkyl, —(CH 2 ), —O—R f , C 3 -C 8 -alkenyl-O—R f , —(CH 2 ) n —NR g R h , —C 2 -C 6 -alkenyl-NR g R h , or —(CH 2 ) n —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         14 . The compound of  claim 13 , selected from the group consisting of: 
 3-(5-Fluoro-pyridin-3-ylamino)-pyrazine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide;    6-Methyl-3-(pyridin-3-ylamino)-pyrazine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide hydrochloride; and    6-Methyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide hydrochloride.    
     
     
         15 . The compound of  claim 1  having formula (Ie)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         16 . The compound of  claim 15 , wherein: 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         17 . The compound of  claim 1  having formula (If)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         18 . The compound of  claim 17 , wherein 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         19 . The compound of  claim 1  having formula (Ig)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         20 . The compound of o  claim 19 , wherein: 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         21 . The compound of  claim 1  having formula (Ih)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         22 . The compound of  claim 21 , wherein: 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         23 . The compound of  claim 1  having formula (Ii)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         24 . The compound of  claim 23 , wherein: 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         25 . The compound of  claim 24 , selected from the group, consisting of 6-Methyl-3-(pyridin-3-ylamino)-pyrazine-2-carboxylic acid (5-fluoro-pyridin-2-yl)-amide hydrochloride; and 6-Methyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid (5-fluoro-pyridin-2-yl)-amide.  
     
     
         26 . The compound of  claim 1  having formula (Ij)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         27 . The compound of  claim 26 , wherein: 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         28 . The compound of  claim 27 , selected from the group consisting of: 
 3-(Pyridin-3-ylamino)-pyrazine-2-carboxylic acid (3-chloro-phenyl)-amide;    3-Phenylamino-pyrazine-2-carboxylic acid (3-chloro-phenyl)-amide; and    6-Methyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid (3-chloro-phenyl)-amide hydrochloride.    
     
     
         29 . The compound of  claim 1  having formula (Ik)  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         30 . The compound of  claim 29 , wherein: 
 R 2  is H or C 1 -C 7 -alkyl;    R 3  is H, phenyl or 5- or 6-membered heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , (CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl; and  
   R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e , or a pharmaceutically acceptable salt thereof.    
     
     
         31 . The compound of  claim 30 , selected from the group consisting of: 
 3-Phenylamino-pyrazine-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide, and    3-(5-Chloro-pyridin-3-ylamino)-6-methyl-pyrazine-2-carboxylic acid (2-methyl-pyridin-4-yl)-amide.    
     
     
         32 . The compound of  claim 1 , wherein 
 R 3  is aryl which is optionally substituted by CN, Cl, F, Br, CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) n —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl.    
     
     
         33 . The compound of  claim 1 , wherein 
 R 3  is heteroaryl which is optionally substituted by CN, Cl, F, Br, CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) n —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl.    
     
     
         34 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is a 5- or 6-membered ring of formula (II) or (III):  
                     
 R 2  is H, C 1 -C 7 -alkyl, C 3 -C 6 -cycloalkyl, or —(CH 2 ) m —R a ;  
 R 3  is H, aryl, or heteroaryl each of which is optionally substituted by: 
 CN, Cl, F, Br, CF 3 , CHF 2 , —O—C 1 -C 7 -alkyl, —(CO)—R b , —(CH 2 ) m —R c , —NH—(CO)—C 1 -C 7 -alkyl, —O—CH 2 F, —O—CHF 2 , —O—CF 3 , —S(O) 2 —R d , or heteroaryl which is optionally substituted by C 1 -C 7 -alkyl;  
 
 R 4  is H, —OH, Cl, F, Br, CN, —CHF 2 , CF 3 , C 1 -C 7 -alkyl, —O—(CO)—C 1 -C 7 -alkyl, or —(CH 2 ) m —R e ;  
 R 5  is C 1 -C 7 -alkyl, C 1 -C 7 -alkyl-C 3 -C 6 -cycloalkyl, —(CH 2 ) n —O—R f , C 3 -C 8 -alkenyl-O—R f , —(CH 2 ), —NR g R h , —C 2 -C 6 -alkenyl-NR g R h , or —(CH 2 ) n —R e ;  
 R a  is —O—C 1 -C 7 -alkyl or —OH;  
 R b  is C 1 -C 7 -alkyl, NH 2 , or —O—C 1 -C 7 -alkyl;  
 R c  is —OH, NH 2 , or NH—(CO)—O—C 1 -C 7 -alkyl;  
 R d  is C 1 -C 7 -alkyl, —NH 2 , —NH—C 1 -C 7 -alkyl, or —N-di(C 1 -C 7 -alkyl);  
 R e  is —OH, —CH 2 F, —CHF 2 , —CF 3 , or —O—(CO)—C 1 -C 7 -alkyl;  
 R f  is C 1 -C 7 -alkyl, C 3 -C 8 -alkenyl, C 3 -C 6 -cycloalkyl, phenyl, benzyl, or —(CO)—R′;  
 R g  and R h  are each independently H. C 1 -C 7 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 8 -alkenyl, phenyl, benzyl, or —(CO)—R′ or R g  and R h , together with the nitrogen atom to which they are attached, form a 5- to 7-membered heterocyclic or heteroaryl ring optionally substituted with 1 or 2OH;  
 R′ is NH 2 , —NH—C 1 -C 7 -alkyl, C 1 -C 7 -alkyl, or C 1 -C 7 -alkoxy;  
 m is 1 to 4; and  
 n is 2 to 6;  
 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

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