Peptide deformylase inhibitors

Abstract

Novel PDF inhibitors and novel methods for their use are provided.

1 . A compound according to Formula (I):  
       
         
           
           
               
               
           
         
       
       wherein, 
 R1 is selected from the group consisting of C 1 -C 9 alkyl, C 1-2 alkylAr, and Ar;  
 R2 is selected from the group consisting of hydrogen, C 1 -C 9 alkyl, C 1-4 alkylAr′, NR4, NC(O)R4, C 2-4 alkylNR3R4, C 1-3 alkylC(O)NR3R4, C 1-3 alkylC(O)Ar′, C 2-3 alkylNHC(O)NR3R4, C 2-3 alkylNHC(O)Ar′, and C 1-2 alkylSO 2 R4;  
 R3 is selected from the group consisting of C 1 -C 9 alkyl, C 1-2 alkylAr, and Ar;  
 R4 is R3, Ar′, or R4 may be taken together with R3 and the nitrogen atom to which they are attached to form a heterocyclic ring which is optionally substituted with one, two, or three substiutents selected from the group consisting of C 1-3 alkyl, aryl, C 1-3 alkoxy (optionally substituted by one to three F), aryloxy, carboxy, oxo, hydroxy, amino, nitro, and cyano, or which may be optionally fused to an aryl, a heteroaryl; or  
 a second heterocyclic ring;  
 Ar is selected from the group consisting of phenyl, furyl, and thienyl, all of which can be optionally substituted with one, two, or three substituents selected from the group consisting of: C 1 -C 3 alkyl, CN, F, Cl, Br, and I;  
 Ar′ is selected from the group consisting of: phenyl, naphthyl, furyl, pyridyl, thienyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolyl, imidazolidinyl, benzofuranyl, indolyl, thiazolidinyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, and pyrimidyl, all of which can be optionally substituted with one, two, or three substituents from the group consisting of: C 1 -C 6 alkyl, C 1 -C 6 alkoxy, (CH 2 ) 0-5 CO 2 R1, C(O)N(R1) 2 , CN, (CH 2 ) 0-5 OH, NO 2 , F, Cl, Br, I, CF 3 , N(R1) 2 , and NHC(O)R1;  
 A is selected from the group of C(O)NHOH or N(CHO)OH;  
 X is NH, when Y is C(O), or X is CH2 when Y is C(O) or CH2.  
 
     
     
         2 . A compound according to  claim 1  selected from the group consisting of: 
 N-[(S)-1-Benzyl-4-pentyl-2,5-dioxo-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-[(S)-1,4-Dibenzyl-2,5-dioxo-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-[(S)-1-Benzyl-4-butyl-2,5-dioxo-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-[(S)-2,5-Dioxo-4-pentyl-1-phenyl-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-[(S)-4-Butyl-1-(3,4-dichloro-benzyl)-2,5-dioxo-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-[(S)-4-Butyl-2,5-dioxo-1-(2-oxo-2-phenyl-ethyl)-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-[(S)-1-Biphenyl-4-ylmethyl-4-butyl-2,5-dioxo-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-[(S)-1-Benzyl-4-cyclohexylmethyl-2,5-dioxo-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-{(S)-4-Butyl-1-[2-(5-chloro-3-methyl-1-benzo[b]thiophen-2-yl)-2-oxo-ethyl]-2,5-dioxo-imidazolidin-4-ylmethyl}-N-hydroxyformamide;    2-{(S)-4-Butyl-4-[(formyl-hydroxy-amino)methyl]-2,5-dioxo-imidazolidin-1-yl}-N-(3,5-dichlorophenyl)acetamide;    2-{(S)-4-Butyl-4-[(formylhydroxyamino)methyl]-2,5-dioxo-imidazolidin-1-ylmethyl}benzoic acid methyl ester;    N-[(S)-4-Butyl-1-(2-morpholin-4-yl-ethyl)-2,5-dioxo-imidazolidin-4-ylmethyl]-N-hydroxyformamide;    N-[(S)-1-(2-Benzofuran-2-yl-2-oxo-ethyl)-4-butyl-2,5-dioxo-imidazolidin-4-ylmethyl]-N-hydroxyformamide; and    2-{(S)-4-Butyl-4-[(formylhydroxyamino)methyl]-2,5-dioxo-imidazolidin-1-ylmethyl}benzoic acid;    or a pharmaceutically acceptable salt thereof.    
     
     
         3 . A method of treating a bacterial infection by administering to a subject in need of treatment a compound according to  claim 1.