Hiv-integrase inhibitors, pharmaceutical compositions, and methods for their use

Abstract

Bicyclic hydroxamate compounds represented by the Formula I: are described. The bicyclic hydroxamate compounds and compositions containing those compounds may be used to inhibit or modulate an enzyme activity of HIV Integrase and to treat HIV mediated diseases and conditions.

1 . (canceled) 
     
     
         2 . A method inhibiting or modulating an enzyme activity of HIV integrase, comprising contacting the enzyme with an effective amount of a compound represented by Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is hydrogen or C(O)OR c , where R c  is an unsubstituted alkyl, unsubstituted alkenyl, or unsubstituted alkynyl; 
 R 2  is hydrogen or an alkyl, alkenyl, or heteroalkyl, unsubstituted or substituted with one or more substituents independently selected from the group consisting of: —O—; NR d R d ; —OR d , halogens; and an aryl group, unsubstituted or substituted with one or more substituents independently selected from the group consisting of: halogens; —C(R d ) 3 ; unsubstituted alkyl; alkyl-R d ; alkenyl-R d ; and aryl groups, 
 where R d  is one or more substituents independently selected from the group consisting of hydrogen; unsubstituted alkyl; unsubstituted alkenyl; and unsubstituted aryl groups; 
 R 3  is hydrogen or an alkyl, alkenyl, or heteroalkyl group, unsubstituted or substituted with one or more substituents independently selected from the group consisting of: —O—; —OR e ; and alkyl, aryl, cycloalkyl, and heteroaryl groups, unsubstituted or substituted with one or more substituents independently selected from the group consisting of: halogens; —OH; and aryl or heteroaryl groups, substituted with one or more R e  substituents, 
 where R e  is one or more substituents independently selected from the group consisting of halogens; hydrogen; OH; unsubstituted alkyl; and aryl unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen and alkyl; 
 R 4  is hydrogen or an alkyl group, unsubstituted or substituted with —OR where R f  is an unsubstituted alkyl group; 
 R 5  is hydrogen or an alkyl group; 
 R 6  is hydrogen or an alkyl group, unsubstituted or substituted with an aryl group; 
 R 4  and R 6  together with the N to which R 6  is attached cyclize to form the following compound represented by the Formula Id: 
 
       
         
           
           
               
               
           
         
       
       wherein R 12  and R 13  are each independently hydrogen; and 
       n is 1;
 R 7  is hydrogen or an alkyl, alkenyl, or aryl group, unsubstituted or substituted with an aryl group, unsubstituted or substituted with one or more halogens: 
 X is C or N; 
 Y is C; 
 Z is C or N; and 
 there is a double bond between X and the 6-membered ring and Z and the 6-membered ring; or between X and Y; or between Y and Z; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         3 . A method according to  claim 2 , wherein said compound of Formula I is represented by Formula Ia: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is N; 
 Y is C; 
 Z is C; and 
 the double bond is between Y and Z; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         4 . A method according to  claim 2 , wherein said compound of Formula I is represented by Formula Ib: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is N; 
 Y is C; 
 Z is N; and 
 the double bond is between Y and Z; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         5 . A method according to  claim 2 , wherein said compound of Formula I is represented by Formula Ic: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is C; 
 Y is C; 
 Z is N; and 
 the double bond is between X and Y; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         6 . A method according to  claim 2 , wherein said compound of Formula I is represented by Formula Ie: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is N; 
 Y is C; 
 Z is N; and 
 the double bond is between X and Y; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         7 . A method according to  claim 2 , wherein for said compound represented by Formula I or pharmaceutically acceptable salt thereof:
 R 1  is hydrogen or —C(O)O-ethyl;   R 2  is hydrogen, methyl, ethyl, propyl, vinyl, allyl, or benzyl, unsubstituted or substituted with one or more substituents independently selected from the group consisting of: halogens, —O—, OH, amino, and phenyl, unsubstituted or substituted with one or more substituents selected from the group consisting of: methyl, ethyl, phenyl, benzyl, 2-phenylethyl, 3-phenylallyl, and 2-phenylvinyl;   R 3  is methyl, ethyl, butyl, or benzyl, unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogens, OH, methyl, cyclohexyl, —O—, thiadiazole, thiophenyl, and phenoxy, unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogens, phenyl, and ethoxy,   R 4  is hydrogen, methyl or methoxymethyl;   R 5  is hydrogen or methyl;   R 6  is hydrogen, methyl, or benzyl;   R 7  is hydrogen, methyl, benzyl, phenyl, allyl, or tertbutyl, unsubstituted or substituted with one or more halogens; and   R 4  and R 6  together with the N to which R 6  attaches cyclize to form a pyrrole-2-one.   
     
     
         8 . A method according to  claim 2 , wherein for said compound represented by Formula I or pharmaceutically acceptable salt thereof
 R 1  is hydrogen or —C(O)O-ethyl;   R 2  is selected from hydrogen; hydroxymethyl; methoxymethyl; ethoxymethyl; 2-phenylvinyl; 3-phenylprop-1-enyl; [(2-phenylvinyl)oxy]methyl; dimethylaminomethyl; benzyloxymethyl; 4-fluorobenzyl; 2-phenylvinyl; 2-phenylethyl; 3-phenylpropyl; 2-phenylethoxymethyl; [(phenylprop-2-enyl)oxy]methyl; [(3-phenylallyl)oxy]methyl; methyl; ethyl; and allyl;   R 3  is selected from hydrogen; 2,4-difluorobenzyl; 2,3-difluorobenzyl; 4-fluorobenzyl; 3-chloro-2,6-difluorobenzyl; 3-chloro-5-fluoro-2-hydroxybenzyl; 5-chloro-thiophen-2-ylmethyl; 3-chloro-2-fluorobenzyl; 2,3-dichlorobenzyl; 5-ethoxy-[1,2,3]thiadiazol-4-ylmethyl; 3-methyl-butyl: 2-cyclohexyl-ethyl; 2,4-difluoro-phenoxymethyl; 3,5-difluoro-2-hydroxybenzyl; 2-chloro-4-fluoro-phenoxymethyl; 3-chloro-5-fluoro-2-hydroxybenzyl; 4-fluoro-phenoxymethyl; 5-fluoro-2-hydroxy-benzyl; 2,3,4-trifluoro-phenoxymethyl; 3,4,5-trifluoro-2-hydroxybenzyl; 2-chloro-phenoxymethyl; and 5-chloro-2-hydroxy-benzyl;   R 4  is hydrogen, methyl or methoxymethyl;   R 5  is hydrogen or methyl;   R 6  is hydrogen, methyl, or benzyl;   R 7  is hydrogen, methyl, benzyl, phenyl, pentafluorobenzyl, allyl, tert-butyl;   R 4  and R 6  together with the N to which R attaches cyclize to form a pyrrol-2-one.   
     
     
         9 . A method according to  claim 2 , wherein said compound of Formula I is selected from the group consisting of: 
       1-(2,4-Difluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(4-Fluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(4-Fluorobenzyl)-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       N-Benzyl-1-(4-fluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(3-Chloro-2,6-difluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(5-Chloro-thiophen-2-ylmethyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(3-Chloro-2-fluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,3-Dichlorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(5-Ethoxy-[1,2,3]thiadiazol-4-ylmethyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-4-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-ethoxymethyl-N-hydroxy-1H-pyrrolo[2,3]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-hydroxymethyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide, 
       1-(2,4-Difluorobenzyl-3-dimethylaminomethyl-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       3-Benzyloxymethyl-1-(2,4-difluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       3-(2,4-Difluorobenzyl)-N-hydroxy-3H-imidazo[4,5-c]pyridine-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-1H-imidazo[4,5-c]pyridine-6-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-ethoxymethyl-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-hydroxymethyl-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-dimethylaminomethyl-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-methoxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-ethoxymethyl-N-methoxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-hydroxymethyl-N-methoxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-dimethylaminomethyl-N-methoxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       N-Benzyloxy-1-(2,4-difluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       N-Benzyloxy-3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(4-Fluorobenzyl)-N-methoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(4-Fluorobenzyl)-N-phenoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(4-Fluorobenzyl)-N-[(pentafluorobenzyl)oxy]-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-(Allyloxy)-3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       6-(2,4-Difluorobenzyl)-2-hydroxy-1,6-dihydrodipyrrolo[3,2-d:3′,4′-b]pyridin-3(2H-one; 
       3-(2,3-Difluorobenzyl)-N-phenoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(2,3-Difluorobenzyl)-N-methoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-Allyloxy-3-(2,3-difluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       1-(4-Fluorobenzyl)-N-phenoxy-1H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-tert-Butoxy-3-(2,3-difluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-Methoxy-3-(3-methyl-butyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(3-Methyl-butyl)-N-phenoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(2-Cyclohexyl-ethyl)-N-phenoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(2-Cyclohexyl-ethyl)-N-methoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-Allyloxy-3-(2-cyclohexyl-ethyl)-3H-imidazo[4,5-c]pyridin-6-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-4-methoxymethyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-(2-phenylvinyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-(3-phenylprop-1-enyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-(2-phenylethyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-phenylpropyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-{[(2-phenylethyl)oxy]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-{[(3-phenylallyl)oxy]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-ethyl-N-hydroxy-1H-pyrrolo[2,3-c]pyridin-5-carboxamide; 
       3-Allyl-1-(2,4-difluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-7-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       Ethyl 1-(2,4-Difluorobenzyl)-5-hydroxycarbamoyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylate; 
       3-(2,4-Difluoro-phenoxymethyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       3-(3,5-Difluoro-2-hydroxybenzyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-]pyridine-6-carboxamide; 
       3-(2-chloro-4-fluoro-phenoxymethyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-carboxamide; 
       3-(3-Chloro-5-fluoro-2-hydroxybenzyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       1-Ethyl-3-(4-fluoro-phenoxymethyl)-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       1-Ethyl-3-(5-fluoro-2-hydroxybenzyl)-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       1-Ethyl-N-hydroxy-3-(2,3,4-trifluoro-2-phenoxymethyl)-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       1-Ethyl-N-hydroxy-3-(3,4,5-trifluoro-2-hydroxybenzyl)-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       3-(2-Chloro-phenoxymethyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-]pyridine-6-carboxamide; 
       3-(5-Chloro-2-hydroxy-benzyl)-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; or a pharmaceutically acceptable salt thereof. 
     
     
         10 . A method treating a disease or condition mediated by HIV, comprising administering to a mammal in need of such treatment a therapeutically effective amount of at least one compound represented by Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is hydrogen or C(O)OR c , where R c  is an unsubstituted alkyl, unsubstituted alkenyl, or unsubstituted alkynyl; 
 R 2  is hydrogen or an alkyl, alkenyl, or heteroalkyl, unsubstituted or substituted with one or more substituents independently selected from the group consisting of:
 —O—; NR d R d ; —OR d ; halogens; and an aryl group, unsubstituted or substituted with one or more substituents independently selected from the group consisting of 
 halogens; —C(R d ) 3 ; unsubstituted alkyl; alkyl-R d ; alkenyl-R d ; and aryl groups, where R d  is one or more substituents independently selected from the group consisting of hydrogen; unsubstituted alkyl; unsubstituted alkenyl; and unsubstituted aryl groups; 
 
 R 3  is hydrogen or an alkyl, alkenyl, or heteroalkyl group, unsubstituted or substituted with one or more substituents independently selected from the group consisting of 
 —O—; —OR d ; and alkyl, aryl, cycloalkyl, and heteroaryl groups, unsubstituted or substituted with one or more substituents independently selected from the group consisting of: 
 halogens; —OH; and aryl or heteroaryl groups, substituted with one or more R e  substituents, 
 
       where R e  is one or more substituents independently selected from the group consisting of halogens; hydrogen; OH; unsubstituted alkyl; and aryl unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen and alkyl:
 R 4  is hydrogen or an alkyl group, unsubstituted or substituted with —OR f  where R f  is an unsubstituted alkyl group; 
 R 5  is hydrogen or an alkyl group; 
 R 6  is hydrogen or an alkyl group, unsubstituted or substituted with an aryl group; 
 R 4  and R 6  together with the N to which R 6  is attached cyclize to form the following compound represented by the Formula Id: 
 
       
         
           
           
               
               
           
         
       
       wherein R 12  and R 13  are each independently hydrogen; and 
       n is 1;
 R 7  is hydrogen or an alkyl, alkenyl, or aryl group, unsubstituted or substituted with an aryl group, unsubstituted or substituted with one or more halogens; 
 X is C or N; 
 Y is C; 
 Z is C or N; and 
 there is a double bond between X and the 6-membered ring and Z and the 6-membered ring; or between X and Y; or between Y and Z; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         11 . A method according to  claim 10 , wherein said compound of Formula I is represented by Formula Ia: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is N; 
 Y is C; 
 Z is C; and 
 the double bond is between Y and Z; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         12 . A method according to  claim 10 , wherein said compound of Formula I is represented by Formula Ib: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is N; 
 Y is C; 
 Z is N; and 
 the double bond is between Y and Z; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         13 . A method according to  claim 10 , wherein said compound of Formula I is represented by Formula Ic: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is C; 
 Y is C; 
 Z is N; and 
 the double bond is between X and Y; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         14 . A method according to  claim 10 , wherein said compound of Formula I is represented by Formula Ie: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is N; 
 Y is C; 
 Z is N; and 
 the double bond is between X and Y; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         15 . A method according to  claim 10 , wherein for said compound represented by Formula I or pharmaceutically acceptable salt thereof
 R 1  is hydrogen or —C(O)O-ethyl;   R 2  is hydrogen, methyl, ethyl, propyl, vinyl, allyl, or benzyl, unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogens, —O—, OH, amino, and phenyl, unsubstituted or substituted with one or more substituents selected from the group consisting of: methyl, ethyl, phenyl, benzyl, 2-phenylethyl, 3-phenylallyl, and 2-phenylvinyl;   R 3  is methyl, ethyl, butyl, or benzyl, unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogens, OH, methyl, cyclohexyl, —O—, thiadiazole, thiophenyl, and phenoxy, unsubstituted or substituted with one or more substituents independently selected from the group consisting of: halogens, phenyl, and ethoxy;   R 4  is hydrogen, methyl or methoxymethyl;   R 5  is hydrogen or methyl;   R 6  is hydrogen, methyl, or benzyl;   R 7  is hydrogen, methyl, benzyl, phenyl, allyl, or tert-butyl, unsubstituted or substituted with one or more halogens; and   R 4  and R 6  together with the N to which R 6  attaches cyclize to form a pyrrole-2-one.   
     
     
         16 . A method according to  claim 10 , wherein for said compound represented by Formula I or pharmaceutically acceptable salt thereof
 R 1  is hydrogen or —C(O)O-ethyl;   R 2  is selected from hydrogen; hydroxymethyl; methoxymethyl; ethoxymethyl; 2-phenylvinyl; 3-phenylprop-1-enyl; [(2-phenylvinyl)oxy]methyl; dimethylaminomethyl; benzyloxymethyl; 4-fluorobenzyl; 2-phenylvinyl; 2-phenylethyl; 3-phenylpropyl; 2-phenylethoxymethyl; [(phenylprop-2-enyl)oxy]methyl; [(3-phenylallyl)oxy]methyl; methyl; ethyl; and allyl;   R 3  is selected from hydrogen; 2,4-difluorobenzyl; 2,3-difluorobenzyl; 4-fluorobenzyl; 3-chloro-2,6-difluorobenzyl; 3-chloro-5-fluoro-2-hydroxybenzyl; 5-chloro-thiophen-2-ylmethyl; 3-chloro-2-fluorobenzyl; 2,3-dichlorobenzyl; 5-ethoxy-[1,2,3]thiadiazol-4-ylmethyl; 3-methyl-butyl; 2-cyclohexyl-ethyl; 2,4-difluoro-phenoxymethyl; 3,5-difluoro-2-hydroxybenzyl; 2-chloro-4-fluoro-phenoxymethyl: 3-chloro-5-fluoro-2-hydroxybenzyl; 4-fluoro-phenoxymethyl; 5-fluoro-2-hydroxy-benzyl; 2,3,4-trifluoro-phenoxymethyl; 3,4,5-trifluoro-2-hydroxybenzyl; 2-chloro-phenoxymethyl; and 5-chloro-2-hydroxy-benzyl;   R 4  is hydrogen, methyl or methoxymethyl;   R 5  is hydrogen or methyl;   R 6  is hydrogen, methyl, or benzyl;   R 7  is hydrogen, methyl, benzyl, phenyl, pentafluorobenzyl, allyl, tert-butyl;   R 4  and R 6  together with the N to which R 6  attaches cyclize to form a pyrrol-2-one.   
     
     
         17 . A method according to  claim 10 , wherein said compound of Formula I is selected from the group consisting of: 
       1-(2,4-Difluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(4-Fluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(4-Fluorobenzyl)-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       N-Benzyl-1-(4-fluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(3-Chloro-2,6-difluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(5-Chloro-thiophen-2-ylmethyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(3-Chloro-2-fluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,3-Dichlorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(5-Ethoxy-[1,2,3]thiadiazol-4-ylmethyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-4-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-ethoxymethyl-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-hydroxymethyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-dimethylaminomethyl-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       3-Benzyloxymethyl-1-(2,4-difluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       3-(2,4-Difluorobenzyl)-N-hydroxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-1H-imidazo[4,5-c]pyridine-6-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-ethoxymethyl-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-hydroxymethyl-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl-3-dimethylaminomethyl-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-methoxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-ethoxymethyl-N-methoxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-hydroxymethyl-N-methoxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-dimethylaminomethyl-N-methoxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       N-Benzyloxy-1-(2,4-difluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       N-Benzyloxy-3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(4-Fluorobenzyl)-N-methoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(4-Fluorobenzyl)-N-phenoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(4-Fluorobenzyl)-N-[pentafluorobenzyl)oxy]-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-(Allyloxy)-3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       6-(2,4-Difluorobenzyl)-2-hydroxy-1,6-dihydrodipyrrolo[3,2-d:3′,4′-b]pyridin-3(2H)-one; 
       3-(2,3-Difluorobenzyl)-N-phenoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(2,3-Difluorobenzyl)-N-methoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-Allyloxy-3-(2,3-difluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       1-(4-Fluorobenzyl)-N-phenoxy-1H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-tert-Butoxy-3-(2,3-difluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-Methoxy-3-(3-methyl-butyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(3-Methyl-butyl)-N-phenoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(2-Cyclohexyl-ethyl)-N-phenoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       3-(2-Cyclohexyl-ethyl)-N-methoxy-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       N-Allyloxy-3-(2-cyclohexyl-ethyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-4-methoxymethyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-(2-phenylvinyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl-N-hydroxy-3-(3-phenylprop-1-enyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-(2-phenylethyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-(3-phenylpropyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-[(2-phenylethyl)oxy]methyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3{[(3-phenylallyl)oxy]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-3-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       1-(2,4-Difluorobenzyl)-3-ethyl-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       3-Allyl-1-(2,4-difluorobenzyl)-N-hydroxy-1H-pyrrolo[2,3-c]pyridine-carboxamide; 
       1-(2,4-Difluorobenzyl)-N-hydroxy-7-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide; 
       Ethyl 1-(2,4-Difluorobenzyl)-5-hydroxycarbamoyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylate; 
       3-(2,4-Difluoro-phenoxymethyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       3-(3,5-Difluoro-2-hydroxybenzyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       3-(2-Chloro-4-fluoro-phenoxymethyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       3-(3-Chloro-5-fluoro-2-hydroxybenzyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-carboxamide; 
       1-Ethyl-3-(4-fluoro-phenoxymethyl)-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-carboxamide; 
       1-Ethyl-3-(5-fluoro-2-hydroxybenzyl)-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       1-Ethyl-N-hydroxy-3-(2,3,4-trifluoro-2-phenoxymethyl)-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       1-Ethyl-N-hydroxy-3-(3,4,5-trifluoro-2-hydroxybenzyl)-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; 
       3-(2-Chloro-phenoxymethyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-carboxamide; 
       3-(5-Chloro-2-hydroxy-benzyl)-1-ethyl-N-hydroxy-1H-pyrrolo[3,2-c]pyridine-6-carboxamide; or a pharmaceutically acceptable salt thereof. 
     
     
         18 . A method of evaluating the HIV integrase modulatory activity of a test compound, comprising:
 a) immobilizing viral DNA on a surface, wherein the viral DNA has been modified to contain a CA base pair overhang at the 5′ end;   b) adding integrase to the immobilized DNA;   c) adding a test compound to the immobilized viral DNA/integrase mixture;   d) obtaining target DNA radiolabeled at both 3′ ends of the ds-DNA   e) combining the immobilized viral DNA/integrase/compound mixture with the radiolabeled target DNA to initiate a reaction;   f) stopping the reaction by adding a stop buffer to the combination of (e); and   g) reading the assay results in a scintillation counter to determine whether the test compound modulates the activity of the integrase.