Peptide deformylase inhibitors

Abstract

PDF inhibitors and novel methods for their use are provided.

What is claimed is:  
     
         1 . A compound according to formula (I):  
       
         
           
           
               
               
           
         
       
       wherein: 
 R1 is selected from the group consisting of C 1-6 alkyl, —C 1-2 alkylAr, and Ar;  
 R2 is selected from the group consisting of hydrogen, C 1-6 alkyl, —(CH 2 ) m OH, —(CH 2 ) n Ar′, —(CH 2 ) n Het, —Ar′, —SO 2 R3, —C(O)R3, —C(O)NHR3, —C(O)OR3, —CH(R4)CONR5R6, and —CH(R4)CO 2 R7;  
 R3 is selected from the group consisting of C 1-6 alkyl, —C 1-2 alkylAr′, and Ar′;  
 R4 is hydrogen, or C 1-6 alkyl;  
 R5 and R6 are independently selected from the group consisting of hydrogen, C 1-6 alkyl, —C 1-2 alkylAr′, and Ar′; or R5, R6 together form a five or six membered cycloalkyl ring which is optionally mono-substituted by —CH 2 OR7;  
 R7 is selected from the group consisting of hydrogen, and C 1-3 alkyl;  
 Ar is selected from the group consisting of phenyl, furyl, and thienyl, all of which may be optionally substituted by one or more Z 1  groups;  
 Ar′ is selected from the group consisting of phenyl, naphthyl, fruyl, pyridyl, thienyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolyl, imidazolidinyl, benzofuranyl, indolyl, thiazolidinyl, isoxazolyl, oxadiazolyl, thiadiazolyl, morpholnyl, piperidinyl, piperazinyl, pyrrolyl, and pyrimidyl, all of which may be optionally substituted by one or more Z 2  groups;  
 Z 1  is independently selected from the group consisting of hydrogen, C 1-3 alkyl, —CN, F, Cl, Br, and I;  
 Z 2  is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkoxy, —(CH 2 ) n CO 2 R4, —C(O)NR5R6, —CN, —(CH 2 ) n OH, —NO 2 , F, Cl, Br, I, —NR5R6, and —NHC(O)R1;  
 m is 2 to 5; and  
 n is 0 to 5.  
 
     
     
         2 . A compound according to  claim 1  selected from the group consisting of: 
 N-[(3S,4R)-4-Butyl-1-(5-hydroxypentyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 N-[(3R,4S)-4-Butyl-1-(5-hydroxypentyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-2-oxo-1-(t-butylcarboxy)pyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-(4-Butyl-2-oxopyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-(4-Butyl-2-oxo-1-pentanoylpyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-2-oxo-1-(2-phenylethanoyl)pyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-2-oxo-1-(1-phenylmethanoyl)pyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-(1-Benzenesulfonyl-4-butyl-2-oxopyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[1-(Butane-1-sulfonyl)-4-butyl-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-1-(naphthalen-2-ylmethanoyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-(1-Benzyl-4-butyl-2-oxopyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[1-(4-ethoxyphenyl)methanoyl]-2-oxopyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[1-(3-ethoxyphenyl)methanoyl]-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[1-(2-ethoxyphenyl)methanoyl]-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-(4-Butyl-2-oxo-1-pyridin-3-ylmethylpyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 N-((3S,4R)-4-Butyl-1-{(S)-1-[1-((S)-2-methoxymethyl-pyrrolidin-1-yl)methanoyl]-3-methylbutyl}-2-oxopyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 N-((3R,4S)-4-Butyl-1-{(S)-1-[1-((S)2-methoxymethylpyrrolidin-1-yl)-methanoyl]-3-methylbutyl}-2-oxopyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 N-((3S,4R)-4-Butyl-1-((S)-1-[1-(dimethylamino)methanoyl]-3,3-dimethylbutyl }-2-oxopyrrolidin-3-yl-methyl)-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-1-(4-ethoxybenzyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-1-(4-hydroxybenzyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[4-(2-morpholin-4-yl-2-oxoethoxy)benzyl]-2-oxopyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[4-(4-carboxy-1-butoxy)benzyl]-2-oxopyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[4-(3-hydroxybenzoxy)benzyl]-2-oxopyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-2-oxo-1-[4-(tetrahydrofuran-2-ylmethoxy)benzyl]pyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[4-(furan-2-ylmethoxy)benzyl]-2-oxopyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[4-(3-hydroxypropoxy)benzyl]-2-oxopyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-2-oxo-1-[4-(piperidin-3-ylmethoxy)benzyl]pyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-2-oxo-1-[4-(pyridin-3-ylmethoxy)benzyl]pyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-(4-Butyl-1-[4-(5-hydroxypentoxy)benzyl]-2-oxopyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-1-(2,3-dichlorobenzyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-1-(3,4-dichlorobenzyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-(4-Butyl-2-oxo-1-phenylpyrrolidin-3-yl-methyl]-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-{4-Butyl-1-[2-(2-hydroxyphenyl)-2-oxoethyl]-2-oxopyrrolidin-3-yl-methyl}-N-hydroxyformamide;  
 (+/−)-(3RS,4SR)-N-[4-Butyl-1-(3,5-dimethylisoxazol-4ylmethyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide; and  
 (+/−)-(3RS,4SR)-N-[4-Butyl-1-(2-methylthiazol-4-ylmethyl)-2-oxopyrrolidin-3-yl-methyl]-N-hydroxyformamide.  
 
     
     
         3 . A method of treating a bacterial infection by administering to a subject in need of treatment a compound according to  claim 1.