Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors

Abstract

Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme and the treatment of certain conditions such as COPD.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is:
 H; 
 (C 3 -C 7 ) cycloalkylcarbonyl; 
 (C 1 -C 6 ) alkyl, optionally substituted by one or more substituents selected from (C 3 -C 7 ) cycloalkyl or (C 5 -C 7 ) cycloalkenyl; 
 (C 1 -C 6 ) haloalkyl; 
 (C 3 -C 7 ) cycloalkyl; 
 (C 5 -C 7 ) cycloalkenyl; 
 (C 2 -C 6 ) alkenyl; or 
 (C 2 -C 6 ) alkynyl; 
 
         R 2  is:
 H; 
 (C 3 -C 7 ) cycloalkylcarbonyl; 
 (C 1 -C 6 ) alkyl, optionally substituted by one or more substituents selected from (C 3 -C 7 ) cycloalkyl or (C 5 -C 7 ) cycloalkenyl; 
 (C 1 -C 6 ) haloalkyl; 
 (C 3 -C 7 ) cycloalkyl; 
 (C 5 -C 7 ) cycloalkenyl; 
 (C 2 -C 6 ) alkenyl; or 
 (C 2 -C 6 ) alkynyl; 
 or, when R 19  is different from hydrogen, R 2  forms together with R 19  a group of formula (x) as defined below; 
 or R 1  and R 2 , together with the interconnecting atoms, form a 2,2-difluoro-1,3-dioxolane ring of formula (q) fused to the phenyl moiety which bears groups —OR 1  and —OR 2 , wherein asterisks indicate carbon atoms shared with such phenyl ring: 
 
       
       
         
           
           
               
               
           
         
         R 19  is hydrogen or, if different from hydrogen, it forms together with R 2  a group of formula (x) wherein bonds labeled with (1) and (2) indicate the points of attachment for group (x) to atoms bearing groups R 19  and R 2  respectively 
       
       
         
           
           
               
               
           
         
         in such a way that R 2  and R 19  together with the interconnecting atoms form a ring of formula (w) which is fused to phenyl ring which bears groups —OR 2  and R 19 , wherein asterisks indicate carbon atoms shared with such phenyl ring: 
       
       
         
           
           
               
               
           
         
         R 3  is one or more substituents independently selected from the group consisting of H, CN, NO 2 , CF 3  and a halogen atom; 
         Z is a group —(CH 2 ) n — wherein n is 0 or 1; 
         A is a saturated and monocyclic (C 3 -C 7 ) heterocycloalkyl-ene group; 
         K is:
 —(CH 2 ) m C(O)R 4  wherein m may be 0 or 1; 
 —C(O)(CH 2 ) j R 4 , wherein j may be 1 or 2; 
 —SO 2  (CH 2 ) p R 4  wherein p may be zero, 1 or 2; 
 —(CH 2 ) y SO 2 R 4  wherein y may be 1 or 2; 
 —(CH 2 ) z R 4  wherein z may be 1 or 2; or 
 —C(O)(CH 2 ) 2 SO 2 R 4 ; 
 R 4  is a ring system, that is a mono- or bicyclic ring which may be saturated, partially unsaturated or fully unsaturated, such as aryl, (C 3 -C 8 ) cycloalkyl, (C 3 -C 7 ) heterocycloalkyl, or heteroaryl, such ring being optionally substituted by one or more groups R 5  which may be the same or different, and which are independently selected from the group consisting of:
 (C 1 -C 6 ) alkyl optionally substituted by one or more groups independently selected in the list consisting of: (C 3 -C 7 ) cycloalkyl, —OH and a group —NR 18 C(O)(C 1 -C 4 ) alkyl, wherein R 18  is hydrogen or (C 1 -C 4 ) alkyl; 
 (C 3 -C 7 ) heterocycloalkyl; 
 5 or 6-membered heteroaryl which is optionally substituted by one or two (C 1 -C 4 ) alkyl groups; 
 (C 1 -C 6 ) haloalkyl; 
 (C 3 -C 7 ) heterocycloalkyl(C 1 -C 4 ) alkyl; 
 a group —OR 6  wherein R 6  is
 H; 
 (C 1 -C 6 ) haloalkyl; 
 a group —SO 2 R 7 , wherein R 7  is (C 1 -C 4 ) alkyl; 
 a group —C(O)R 7  wherein R 7  is (C 1 -C 4 ) alkyl; 
 (C 1 -C 10 ) alkyl optionally substituted by one or more (C 3 -C 7 ) cycloalkyl groups or by a group —NR 8 R 9  as below defined; or 
 (C 3 -C 7 ) cycloalkyl; 
 
 a group —SR 20  wherein R 20  is
 H; 
 (C 1 -C 6 ) haloalkyl; 
 a group —C(O)R 7  wherein R 7  is (C 1 -C 4 ) alkyl; 
 (C 1 -C 10 ) alkyl optionally substituted by one or more (C 3 -C 7 ) cycloalkyl groups or by a group —NR 8 R 9 ; or 
 (C 3 -C 7 ) cycloalkyl; 
 
 a halogen atom; 
 CN; 
 NO 2 ; 
 NR 8 R 9  wherein R 8  and R 9  are different or the same and are independently selected from the group consisting of:
 H; 
 (C 1 -C 4 ) alkylene-NR 13 R 14  wherein R 13  and R 14  are different or the same and are independently selected from the group consisting of: H and (C 1 -C 6 ) alkyl, which is optionally substituted with (C 3 -C 7 ) cycloalkyl or (C 3 -C 7 ) heterocycloalkyl; or they form with the nitrogen atom to which they are linked a saturated or partially saturated (C 3 -C 7 ) heterocyclic ring; 
 (C 1 -C 6 ) alkyl, optionally substituted with (C 3 -C 7 ) cycloalkyl, (C 3 -C 7 ) heterocycloalkyl, a group —OH or (C 1 -C 6 ) alkoxyl; 
 a group —SO 2 R 15 , wherein R 15  is selected in the group consisting of: (C 1 -C 4 ) alkyl optionally substituted by (C 3 -C 7 ) cycloalkyl or (C 3 -C 7 ) heterocycloalkyl; (C 3 -C 7 ) heterocycloalkyl; and phenyl optionally substituted by one or more (C 1 -C 6 ) alkyl, halogen or a group —OH; 
 a group —C(O)R 16 , wherein R 16  is selected in the group consisting of: (C 1 -C 6 ) alkyl optionally substituted by (C 3 -C 7 ) cycloalkyl or (C 3 -C 7 ) heterocycloalkyl; (C 3 -C 7 ) heterocycloalkyl; phenyl optionally substituted by one or more (C 1 -C 6 ) alkyl, halogen or —OH; and a group —NH 2 ; 
 a group —C(O)OR 17 , wherein R 17  is selected in the group consisting of: (C 1 -C 6 ) alkyl optionally substituted by (C 3 -C 7 ) cycloalkyl or (C 3 -C 7 ) heterocycloalkyl; (C 3 -C 7 ) heterocycloalkyl; phenyl optionally substituted by one or more (C 1 -C 6 ) alkyl, halogen or —OH; and a group —NH 2 ; 
 or they form with the nitrogen atom to which they are linked a saturated or partially saturated heterocyclic ring, which is optionally substituted by one or more (C 1 -C 6 ) alkyl or oxo groups; 
 
 (C 1 -C 4 ) alkylene-NR 8 R 9  as above defined; 
 COR 10  wherein R 10  is phenyl or (C 1 -C 6 ) alkyl; 
 oxo; 
 —SO 2 R 11  wherein R 11  is (C 1 -C 4 ) alkyl, —OH or —NR 5 R 9  wherein R 8  and R 9  are as defined above; 
 —COOR 12  wherein R 12  is H, (C 1 -C 4 ) alkyl or (C 1 -C 4 ) alkylene-NR 8 R 9  wherein R 8  and R 9  are as defined above; and 
 —CONR 8 R 9  wherein R 8  and R 9  are as defined above; 
 
 wherein groups R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20  may be the same or different at each occurrence, if present in more than one group; 
 an N-oxide derivative on the pyridine ring, or a pharmaceutically acceptable salt thereof. 
 
       
     
     
         2 . A compound according to  claim 1 , which is represented by formula (IC): 
       
         
           
           
               
               
           
         
         an N-oxide derivative on the pyridine ring, or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . A compound according to  claim 1 , which is represented by formula (IF): 
       
         
           
           
               
               
           
         
         Wherein: 
         Z is a bond, 
         A is a (C 3 -C 7 ) heterocycloalkyl-ene group comprising a nitrogen atom which represents the connecting point to group K, 
         K is a group selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         R 4  is a phenyl group or a 5 or 6-membered heteroaryl group, each R 4  being optionally substituted by one or more groups R 5 ; 
         An N-oxide derivative on the pyridine ring, or a pharmaceutically acceptable salt thereof. 
       
     
     
         4 . A pyridine N-oxide according to  claim 1 , which is represented by formula (IH): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         5 . A compound according to  claim 1 , which is represented by formula (I)′: 
       
         
           
           
               
               
           
         
       
       an N-oxide derivative on the pyridine ring, or a pharmaceutically acceptable salt thereof. 
     
     
         6 . A pyridine N-oxide according to  claim 1 , which is represented by formula (IDa): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         7 . A compound according to  claim 1 , which is selected from the group consisting of:
 3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(4-methoxy-3-(methylsulfonyloxy)benzoyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3,4-dimethoxyphenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((2S)-2-(3-(4-aminophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(methylsulfonamido)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(N-(2-morpholinoethyl)methylsulfonamido)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((R)-3-(4-aminophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   4-((S)-2-((S)-3-(4-aminophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   4-((S)-2-((S)-1-(4-aminophenylsulfonyl)pyrrolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-((4-(methoxycarbonyl)-5-methylfuran-2-yl)methyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)-4-methoxyphenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R or S)-4-(3-sulfamoylphenylsulfonyl)morpholine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(2-oxo-2-(thiophen-2-yl)ethyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S or R)-3-(4-(dimethylcarbamoyl)benzyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S or R)-3-(4-(dimethylcarbamoyl)benzyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((2S)-2-(3-(4-aminobenzoyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(4-(3-(dimethylcarbamoyl)phenylsulfonyl)thiomorpholine-3-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(4-(4-(N-methylsulfamoyl)phenylsulfonyl)thiomorpholine-3-carbonyloxy)ethyl)pyridine 1-oxide;   4-((2S)-2-(3-(3-amino-4-methoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((R)-3-(4-aminophenylsulfonyl)thiazolidine-4-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   4-((2S)-2-(4-(4-aminophenylsulfonyl)morpholine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(4-(3-(dimethylcarbamoyl)phenylsulfonyl)morpholine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-4-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(1,3-dioxoisoindolin-5-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-sulfamoylphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((2S)-2-(3-(3-carboxy-4-methoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-fluorophenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(2,4-dimethylphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(thiophen-2-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(dimethylcarbamoyl)-4-methoxyphenyl sulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(4-(3-(dimethylcarbamoyl)phenylsulfonyl)piperazin-1-yl)acetoxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(4-methylpiperazine-1-carbonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(3-chlorophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(1-methyl-1H-imidazol-2-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(pyridin-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(2,4-difluorophenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(2-chloro-4-fluorophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-fluoro-2-methylphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(2-chlorophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclohexylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(thiophen-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(cyclopropylmethoxy)-5-(N-(2-morpholinoethyl)methylsulfonamido)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3,4-dimethoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   (S)-4-(2-(2-(4-(4-aminophenylsulfonyl)piperazin-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)-4-methoxyphenylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(6-morpholinopyridin-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-methoxy-3-(4-methylpiperazine-1-carbonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-methoxy-3-(morpholine-4-carbonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S or R)-3-(4-methoxy-3-(morpholinomethyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropyl methoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(N,N-dimethylsulfamoyl)-4-methoxybenzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S or R)-3-(3-carboxyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(morpholinomethyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(4-(phenylsulfonyl)morpholine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3,5-dimethylisoxazol-4-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(thiazole-5-carbonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-((dimethylamino)methyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(oxazole-5-carbonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(4-methylpiperazine-1-carbonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(1-methyl-1H-imidazol-2-ylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(5-(methoxycarbonyl)thiophen-2-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(pyridin-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(dimethylcarbamoyl)-4-methoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(1-methyl-1H-imidazol-2-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-sulfamoylphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(methylsulfonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3,4-dimethoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(5-((dimethylamino)methyl)thiophene-2-carbonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((2S)-2-(3-(4-(2-aminoethyl)benzoyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(N-methylsulfamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(furan-2-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(furan-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(N,N-dimethylsulfamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3,4-dimethoxyphenylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(pyridin-3-ylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(methoxycarbonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-(methoxycarbonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-4-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-methoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(trifluoromethoxy)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(1,1-dioxothiomorpholinobenzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-(4-carbamoylbenzoyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(6-morpholinopyridin-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S or R)-3-(4-(aminomethyl)picolinoyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-methoxy-4-methylphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2,4-dimethylthiazol-5-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-picolinoylthiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S or R)-3-(3-((2-morpholinoethoxy)carbonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-methoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(6-morpholinopyridin-3-ylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(di fluoromethoxy)phenyl)-2-((S)-1-(4-nitrophenylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(N,N-dimethylsulfamoyl)phenylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(phenylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2,5-dimethoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(1-methyl-1H-imidazol-2-ylsulfonyl)piperidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-(3-acetylphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(morpholinomethyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide:   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(1,1-dioxothiomorpholinomethyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-(3-(aminomethyl)benzoyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(oxazol-5-yl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-(3-aminophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(methylsulfonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(4-methylpiperazine-1-carbonyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(N-methylsulfamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(1-methyl-1H-imidazol-4-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-phenylacetyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-((S)-3-(2-cyclopropylacetyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(phenylsulfonyl)propanoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-morpholinopropanoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(4-methylpiperazin-1-yl)propanoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)benzoyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-(2-((S)-1-benzoylpyrrolidin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-((S)-1-(3-(dimethylcarbamoyl)benzoyl)pyrrolidin-2-yl)acetoxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-(3-(dimethylcarbamoyl)phenyl)acetyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(2-(3-(dimethylcarbamoyl)phenyl)acetyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-((S)-3-(2-cyanophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-((S)-3-(2-cyano-5-methylphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2,5-dimethylthiophen-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-(4-bromo-2-fluoro-5-methylphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   4-((S)-2-((S)-3-(3-bromo-4-methylphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-((S)-3-(4-cyanophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-((S)-3-(3-cyanophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-(4-(1H-pyrazol-1-yl)phenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-((S)-3-(3-cyano-4-fluorophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(di fluoromethoxy)phenyl)-2-((S)-3-(1-methyl-2-oxoindolin-5-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-((S)-3-(2-chloro-5-cyanophenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(5-methylbenzo[b]thiophen-2-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(1-methyl-1H-pyrazol-3-yl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(difluoromethoxy)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-((S)-3-(4-chloro-2-(trifluoromethyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(5-fluoro-2-methoxyphenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-(benzo[b]thiophen-2-ylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(2-oxopyrrolidin-1-yl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-(1-acetyl-1,2,3,4-tetrahydroquinolin-6-ylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   4-((S)-2-((S)-3-(4-(2-acetamidoethyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(4-(2,2,2-trifluoroethoxy)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-(2-((S)-3-(benzylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(phenethylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-1-(benzylsulfonyl)pyrrolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-3-(1-methyl-2-oxoindolin-5-ylsulfonyl)thiazolidine-4-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-1-(phenylsulfonyl)piperidine-3-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(R)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)piperidine-3-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(phenylsulfonyl)piperidine-3-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)piperidine-3-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(R)-4-(phenylsulfonyl)morpholine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(R)-4-(3-(dimethylcarbamoyl)phenylsulfonyl)morpholine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-4-(phenylsulfonyl)morpholine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-4-(3-(dimethylcarbamoyl)phenylsulfonyl)morpholine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-((S)-1-(phenylsulfonyl)pyrrolidin-2-yl)acetoxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidin-2-yl)acetoxy)ethyl)pyridine 1-oxide;   4-((S)-2-(2-((S)-1-(benzylsulfonyl)pyrrolidin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-oxo-2-phenylethyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(di fluoromethoxy)phenyl)-2-((S)-1-(2-oxo-2-phenylethyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-1-benzylpyrrolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)benzyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-(3-(dimethylcarbamoyl)phenyl)-2-oxoethyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(2-(3-(dimethylcarbamoyl)phenyl)-2-oxoethyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(cyclopropylmethyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((S)-3-benzylthiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(dimethylcarbamoyl)benzyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-phenethylthiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-((S)-1-(3-(dimethylcarbamoyl)benzyl)pyrrolidin-2-yl)acetoxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-ureidophenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(di fluoromethoxy)phenyl)-2-((S)-3-(3-(hydroxymethyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((2S)-2-(2-(3-benzoylthiazolidin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(3-(dimethylcarbamoyl)benzoyl)thiazolidin-2-yl)acetoxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(phenylsulfonyl)thiazolidin-2-yl)acetoxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((2S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidin-2-yl)acetoxy)ethyl)pyridine 1-oxide;   (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-(3-(dimethylcarbamoyl)phenylsulfonyl)azetidine-3-carbonyloxy)ethyl)pyridine 1-oxide;   (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-(phenylsulfonyl)azetidine-3-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)azetidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(phenylsulfonyl)azetidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(1-methyl-2-oxoindolin-5-ylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-morpholinoethylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(2-(4-methylpiperazin-1-yl)ethylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(2-(phenylsulfonyl)ethyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(dimethylcarbamoyl)benzylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(4-(difluoromethoxy)-3-methoxyphenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(4-(difluoromethoxy)-3-methoxyphenyl)-2-((S)-3-(phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S or R)-2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(4-(difluoromethoxy)-3-methoxyphenyl)-2-((S)-1-(phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(4-(difluoromethoxy)-3-methoxyphenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3,4-dimethoxyphenyl)-2-((S)-1-(phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3,4-dimethoxyphenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-((S)-1-(phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-methoxyphenyl)-2-(1-(phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-methoxyphenyl)-2-(1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S or R)-2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-(4-methoxyspiro[benzo[d][1,3]dioxole-2,1′-cyclopentane]-7-yl)-2-((S)-1-(phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)-2-(4-methoxyspiro[benzo[d][1,3]dioxole-2,1′-cyclopentane]-7-yl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-methoxyphenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-methoxyphenyl)-2-((S)-3-(phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-((S)-3-(phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3,4-dimethoxyphenyl)-2-((S)-3-(phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3,4-dimethoxyphenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-(4-methoxyspiro[benzo[d][1,3]dioxole-2,1′-cyclopentane]-7-yl)-2-((S)-3-(phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-(2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(4-methoxyspiro[benzo[d][1,3]dioxole-2,1′-cyclopentane]-7-yl)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(N,N-dimethylsulfamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-methylisoxazolo[5,4-b]pyridin-5-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-5-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(1-methyl-5-(methylcarbamoyl)-1H-pyrrol-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(5-(pyrrolidine-1-carbonyl)-1H-pyrrol-3-ylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   (S)-((S)-1-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,5-dichloropyridin-4-yl)ethyl) 3-(1-methyl-1H-imidazol-2-ylsulfonyl)thiazolidine-2-carboxylate;   4-((S)-2-((S)-3-(1H-1,2,4-triazol-5-ylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   4-((S)-2-((S)-3-benzoylthiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(dimethylcarbamoyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-1-(phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   4-((S)-2-((R)-1-benzoylpyrrolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-1-(3-(dimethylcarbamoyl)benzoyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((R)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((R)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-(dimethylcarbamoyl)phenylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   (S)-((S)-1-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,5-dichloropyridin-4-yl)ethyl) 3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carboxylate;   3,5-dichloro-4-((R)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((R)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(4-(difluoromethoxy)-3-hydroxyphenyl)-2-((S)-3-(3-(dimethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-ylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-1-(3-methylisoxazolo[5,4-b]pyridin-5-ylsulfonyl)pyrrolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-3-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-ylsulfonyl)thiazolidine-4-carbonyloxy)ethyl)pyridine 1-oxide;   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-3-(3-methylisoxazolo[5,4-b]pyridin-5-ylsulfonyl)thiazolidine-4-carbonyloxy)ethyl)pyridine 1-oxide; and   3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(methylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide;   or a pharmaceutically acceptable salt thereof.   
     
     
         8 . A process for preparing a compound of formula (IDa) according to  claim 6 , comprising:
 (1) reacting a compound of formula (XV) with a compound of formula (XIV), to obtain a compound of formula (XII):   
       
         
           
           
               
               
           
         
       
       by: a) adding a compound of formula (XIV), 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) hydrochloride to a solution of a compound of formula (XV) in dimethylformamide, to obtain a mixture; b) stirring said mixture; c) pouring the mixture into cold water, to obtain a precipitate; and d) filtering the precipitate;
 (2) converting said compound of formula (XII) to a compound of formula (XI): 
 
       
         
           
           
               
               
           
         
       
       by: a) adding, with stirring, a solution of concentrated HCl in dry ethyl acetate (9 vol.) to a solution of said compound of formula (XII) in ethyl acetate at room temperature; b) stirring, to obtain a precipitated solid; c) filtering said precipitated solid; and optionally d) washing said precipitated solid with ethyl acetate; and
 (3) reacting said compound of formula (XI) with a compound of formula (VII), to obtain said compound of formula (IDa): 
 
       
         
           
           
               
               
           
         
       
       by: a) adding a solution of a compound of formula (VII) in pyridine to a refrigerated solution of said compound of formula (XI), in pyridine; b) stirring the resulting solution at room temperature; c) pouring the solution into aqueous HCl in excess, to obtain a precipitate; d) filtering said precipitated material and washing it with water or d′) extracting the aqueous phase with ethyl acetate, washing with HCl 1M, brine and evaporating the resulting organic phase; f) dissolving the compounds in ethanol (8 vol); g) vigorously stirring overnight at room temperature; and h) filtering the solid formed;
 wherein R 1 , R 2 , R 3 , R 4  and p in compounds of formulas (XV), (XIV), (XII), (XI), (VII) and (IDa) have meanings as per compounds of formula (I). 
 
     
     
         9 . A combination of a compound, N-oxide, or pharmaceutically acceptable salt according to  claim 1  with a second pharmaceutical active component selected from the group consisting of a beta2-agonist, a corticosteroid, and an antimuscarinic agent. 
     
     
         10 . A pharmaceutical composition, comprising a compound, N-oxide, or pharmaceutically acceptable salt according to  claim 1  and one or more pharmaceutically acceptable carriers and/or excipients. 
     
     
         11 . A pharmaceutical composition, comprising a combination according to  claim 9  and one or more pharmaceutically acceptable carriers and/or excipients. 
     
     
         12 . A method for prevention and/or treatment of a disease of the respiratory tract characterized by airway obstruction, such as asthma or COPD, said method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound, N-oxide, or pharmaceutically acceptable salt according to  claim 1 . 
     
     
         13 . A method for prevention and/or treatment of allergic rhinitis, said method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound, N-oxide, or pharmaceutically acceptable salt according to  claim 1 . 
     
     
         14 . A method for prevention and/or treatment of atopic dermatisis, said method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound, N-oxide, or pharmaceutically acceptable salt according to  claim 1 . 
     
     
         15 . A device comprising a pharmaceutical composition according to  claim 10 . 
     
     
         16 . A device comprising a pharmaceutical composition according to  claim 11 . 
     
     
         17 . A kit comprising a pharmaceutical composition according to  claim 10  and a device which is a single- or multi-dose dry powder inhaler, a metered dose inhaler, or a soft mist nebulizer. 
     
     
         18 . A kit comprising a pharmaceutical composition according to  claim 11  and a device which is a single- or multi-dose dry powder inhaler, a metered dose inhaler, or a soft mist nebulizer.