US2004220231A1PendingUtilityA1
Substituted pyridines useful for inhibiting cholesteryl ester transfer protein activity

Priority: Feb 13, 1998Filed: May 25, 2004Published: Nov 4, 2004
Est. expiryFeb 13, 2018(expired)· nominal 20-yr term from priority
Inventors:Len F. Lee Kevin C. Glenn Daniel T. Connolly David Corley Daniel L. Flynn Ashton T. Hamme Shridhar Hegde Michele A. Melton Roger Schilling James A. Sikorski Nancy N. Wall Jeffery A. Zablocki
A61K 31/44
PatentIndex Score
Cited by
References
Claims
Abstract

A class of substituted pyridines that are useful for inhibiting the activity of cholesteryl ester transfer protein, and have the structural formula (IA), wherein R 2 , R 3 , R 4 , R 5 , and R 6 are defined in the claims.
Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method for inhibiting the activity of cholesteryl ester transfer protein in vivo by administering to a subject a therapeutically effective amount of a compound of Formula I:  
       
         
           
           
               
               
           
         
         wherein:  
         R 2  and R 6  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, fluorinated alkyl, fluorinated aralkyl, chlorofluorinated alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, alkoxyalkyl, and alkoxycarbonyl; provided that at least one of R 2  and R 6  is fluorinated alkyl, chlorofluorinated alkyl or alkoxyalkyl;  
         R 3  is selected from the group consisting of hydroxy, amido, arylcarbonyl, heteroarylcarbonyl, hydroxymethyl  
         —CHO,  
         —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, alkyl and cyanoalkyl; and  
         
           
             
             
                 
                 
             
           
           wherein R 15a  is selected from the group consisting of hydroxy, hydrogen, halogen, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy and heterocyclyloxy, and  
           R 16a  is selected from the group consisting of alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, and heterocyclyl, arylalkoxy, trialkylsilyloxy;  
         
         R 4  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, heteroarylalkenyl, heterocyclylalkenyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkanoyloxy, alkenoyloxy, alkynoyloxy, aryloyloxy, heteroaroyloxy, heterocyclyloyloxy, alkoxycarbonyl, alkenoxycarbonyl, alkynoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heterocyclyloxycarbonyl, thio, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, alkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclylthioalkenyl, alkylamino, alkenylamino, alkynylamino, arylamino, heteroarylamino, heterocyclylamino, aryldialkylamino, diarylamino, diheteroarylamino, alkylarylamino, alkylheteroarylamino, arylheteroarylamino, trialkylsilyl, trialkenylsilyl, triarylsilyl, 
 —OC(O)N(R 8a R 8b ), wherein R 8a  and R 8b  are independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl,  
 —SO 2 R 9 , wherein R 9  is selected from the group consisting of hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl,  
 —OP(O) (OR 10a ) (OR 10b ), wherein R 10a  and R 10b  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and  
 —OP(S) (OR 11a ) (OR 11b ), wherein R 11a  and R 11b  are independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
 
         R 5  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkylcarbonyloxyalkyl, alkenylcarbonyloxyalkyl, alkynylcarbonyloxyalkyl, arylcarbonyloxyalkyl, heteroarylcarbonyloxyalkyl, heterocyclylcarbonyloxyalkyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, heteroarylalkenyl, heterocyclylalkenyl, alkylthioalkyl, cycloalkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclylthioalkenyl, alkoxyalkyl, alkenoxyalkyl, alkynoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, heterocyclyloxyalkyl, alkoxyalkenyl, alkenoxyalkenyl, alkynoxyalkenyl, aryloxyalkenyl, heteroaryloxyalkenyl, heterocyclyloxyalkenyl, cyano, hydroxymethyl,  
         —CO 2 R 14 , 
 wherein R 14  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
                     
 wherein R 15b  is selected from the group consisting of hydroxy, hydrogen, halogen, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, aroyloxy, and alkylsulfonyloxy, and  
 R 16b  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, arylalkoxy, and trialkylsilyloxy;  
                     
 wherein R 17  and R 18  are independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
                     
 wherein R 19  is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, —SR 20 , —OR 21 , and —R 22 CO 2 R 23 , wherein  
 R 20  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aminoaryl, aminoheteroaryl, aminoheterocyclyl, alkylheteroarylamino, arylheteroarylamino,  
 R 21  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl,  
 R 22  is selected from the group consisting of alkylene or arylene, and  
 R 23  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 wherein R 24  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, aralkyl, aralkenyl, and aralkynyl;  
                     
 wherein R 25  is heterocyclylidenyl;  
                     
 wherein R 26  and R 27  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 wherein R 28  and R 29  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 wherein R 30  and R 3 , are independently alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, and heterocyclyloxy; and  
                     
 wherein R 32  and R 33  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 
         —C≡C—Si(R 36 ) 3 , 
 wherein R 36  is selected from the group consisting of alkyl, alkenyl, aryl, heteroaryl and heterocyclyl;  
                     
 wherein R 37  and R 38  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 wherein R 39  is selected from the group consisting of hydrogen, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio and heterocyclylthio, and  
 R 40  is selected from the group consisting of haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, haloheterocyclyl, cycloalkyl, cycloalkenyl, heterocyclylalkoxy, heterocyclylalkenoxy, heterocyclylalkynoxy, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio and heterocyclylthio;  
 
         —N═R 41 , 
 wherein R 41  is heterocyclylidenyl;  
                     
 wherein R 42  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl, and  
 R 43  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, and haloheterocyclyl;  
                     
 wherein R 44  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
 
         —N═S═O;  
         —N═C═S;  
         —N═C═O;  
         —N 3 ;  
         —SR 45 , 
 wherein R 45  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, haloheterocyclyl, heterocyclyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, heteroarylalkenyl, heterocyclylalkenyl, alkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclylthioalkenyl, aminocarbonylalkyl, aminocarbonylalkenyl, aminocarbonylalkynyl, aminocarbonylaryl, aminocarbonylheteroaryl, and aminocarbonylheterocyclyl,  
 
         —SR 46 , and —CH 2 R 47 , 
 wherein R 46  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and  
 R 47  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl; and  
                     
 wherein R 48  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and  
 R 49  is selected from the group consisting of alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl and haloheterocyclyl;  
                     
 wherein R 50  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy and heterocyclyloxy;  
                     
 wherein R 51  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl and haloheterocyclyl; and  
                     
 wherein R 53  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
 
         or a pharmaceutically acceptable salt or tautomer thereof,  
         provided that when R 5  is selected from the group consisting of heterocyclylalkyl and heterocyclylalkenyl, the heterocyclyl radical of the corresponding heterocyclylalkyl or heterocyclylalkenyl is other than a δ-lactone; and  
         provided that when R 4  is aryl, heteroaryl or heterocyclyl, and one of R 2  and R 6  is trifluoromethyl, then the other of R 2  and R 6  is difluoromethyl.  
       
     
     
         2 . The method of  claim 1  wherein: 
 R 2  and R 6  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, fluorinated alkyl, chlorofluorinated alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, alkoxyalkyl, and alkoxycarbonyl; provided that at least one of R 2  and R 6  is fluorinated alkyl, chlorofluorinated alkyl or alkoxyalkyl;  
 R 3  is selected from the group consisting of hydroxy, amido, arylcarbonyl, heteroarylcarbonyl, hydroxymethyl,  
 —CO 2 R 7 , 
 wherein R 7  is selected from the group consisting of hydrogen, alkyl and cyanoalkyl; and  
                     
 wherein R 15a  is selected from the group consisting of hydroxy, halogen, alkylthio and alkoxy, and  
 R 16a  is selected from the group consisting of alkyl, aryl and heteroaryl;  
 
 R 4  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, cycloalkyl, haloalkyl, alkenyl, aryl, heteroaryl, cycloalkylalkyl, heteroarylalkyl, aralkenyl, alkoxy, aralkoxy, alkoxycarbonyl, arylcarbonyloxy, thio, alkylthio, arylthio, cycloalkylthio, heterocyclylthio, alkylthioalkyl, alkylamino, trialkylsilyl,  
 —OC(O)N (R 8 ) 2 , wherein R 9  is aryl,  
 —SO 2 R 9 , wherein R 9  is aryl,  
 —OP(O)(OR 10 ) 2 , wherein R 10  is alkyl, and  
 —OP(S)(OR 11 ) 2 , wherein R 11  is alkyl;  
 R 5  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, haloalkyl, alkynyl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylcarbonyloxyalkyl, heterocyclylalkyl, alkylthioalkyl, arylthioalkyl, heteroarylthioalkyl, alkoxyalkenyl, cyano, hydroxymethyl,  
 CO 2 R 14 , 
 wherein R 14  is alkyl;  
                     
 wherein R 15b  is selected from the group consisting of hydroxy, hydrogen, halogen, alkylthio and alkoxy, and  
 R 16b  is selected from the group consisting of alkyl, aryl and heteroaryl;  
                     
 wherein R 17  and R 18  are independently alkyl;  
                     
 wherein R 19  is selected from the group consisting of aryl, heteroaryl, —SR 20 , —OR 21 , and —R 22 CO 2 R 23 ,  
 wherein R 20  is selected from the group consisting of alkyl, aryl and aminoalkyl,  
 R 21  is aryl,  
 R 22  is alkylene, and  
 R 23  is alkyl;  
                     
 wherein R 24  is selected from the group consisting of hydrogen, unsubstituted alkyl, and aralkyl;  
                     
 wherein R 25  is heterocyclylidenyl;  
                     
 wherein R 26  and R 27  are independently alkyl;  
                     
 wherein R 28  and R 29  are independently alkyl;  
                     
 wherein R 30  and R 31  are independently alkoxy;  
                     
 wherein R 32  is selected from the group consisting of hydrogen and alkyl, and  
 R 33  is alkyl;  
                     
 
 —C≡C—Si(R 36 ) 3 , 
 wherein R 36  is alkyl;  
                     
 wherein R 37  and R 38  are independently alkyl;  
                     
 wherein R 39  is selected from the group consisting of hydrogen, alkoxy, and alkylthio, and  
 R 40  is selected from the group consisting of haloalkyl, cycloalkyl, heterocyclylalkoxy, and alkylthio;  
 
 —N═R 41 , wherein R 41  is heterocyclylidenyl;  
                     wherein R 42  is selected from the group consisting of hydrogen and alkyl, and    R 43  is selected from the group consisting of cycloalkyl, chlorinated alkyl and substituted heteroaryl;                          wherein R 44  is heteroaryl;    
 —N═S═O;  
 —N═C═S;  
 —N═C═O;  
 —N 3 ,  
 —SR 45 , 
 wherein R 45  is selected from the group consisting of hydrogen, alkyl, haloalkyl, heterocyclyl, aralkyl, heteroaralkyl, alkylthioalkyl, aminocarbonylalkyl, —SR 46 , and —CH 2 R 47 ,  
 wherein R 46  is selected from the group consisting of aryl and heteroaryl, and  
 R 47  is selected from the group consisting of aryl and heteroaryl; and  
                     
 wherein R 48  is selected from the group consisting of hydrogen and alkyl, and  
 R 49  is selected from the group consisting of alkoxy and haloalkyl;  
                     
 wherein R 50  is selected from the group consisting of alkyl, alkoxy, aryl and heteroaryl;  
                     
 wherein R 51  is selected from the group consisting of haloalkyl and alkyl; and  
                     
 wherein R 53  is aryl;  
 
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that when R 5  is heterocyclylalkyl or heterocyclylalkenyl, then the heterocyclyl radical is other than a δ-lactone and the alkyl or alkenyl radical is other than —CH 2 CH 2 — or —CH═CH—.  
 
     
     
         3 . The method of  claim 2  wherein: 
 when R 2  is difluoromethyl, R 3  is —CO 2 CH 3 , R 5  is  
                     
 R 6  is trifluoromethyl, and R 19  is the heteroaryl 1-pyrazolyl, then R 4  is selected from the group consisting of hydrogen, hydroxy, halogen, alkoxy, cycloalkyl, haloalkyl, alkenyl, aryl, heteroaryl, cycloalkylalkyl, heteroarylalkyl, aralkenyl, alkoxy, aralkoxy, alkoxycarbonyl, arylcarbonyloxy, thio, alkylthio, arylthio, cycloalkylthio, heterocyclylthio, alkylthioalkyl, trialkylsilyl,  
 —OC(O)N(R 8 ) 21  wherein R 8  is aryl,  
 —SO 2 R 9 , wherein R 9  is aryl,  
 —OP(O)(OR 10 ) 2 , wherein R 10  is alkyl, and  
 —OP(S)(OR 11 ) 2 , wherein R 11  is alkyl; and  
 when R 2  is difluoromethyl, R 3  is —CO 2 CH 3 , R 5  is the heterocyclyl 2-(4,5-dihydro-oxazolyl), and R 6  is trifluoromethyl, then R 4  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, cycloalkyl, haloalkyl, alkenyl, aryl, heteroaryl, heteroarylalkyl, aralkenyl, alkoxy, aralkoxy, alkoxycarbonyl, arylcarbonyloxy, thio, alkylthio, arylthio, cycloalkylthio, heterocyclylthio, alkylthioalkyl, alkylamino, trialkylsilyl,  
 —OC(O)N(R 8 ) 2 , wherein R 8  is aryl,  
 —SO 2 R 9 , wherein R 9  is aryl,  
 —OP(O)(OR 10 ) 2 , wherein R 10  is alkyl, and  
 —OP(S)(OR 11 ) 2 , wherein R 11  is alkyl; and  
 when R 2  and R 6  are independently fluorinated methyl, R 3  is —CO 2 R 7 , R 5  is cyano, and R 7  is selected from the group consisting of hydrogen and alkyl, then R 4  is selected from the group consisting of hydrogen, hydroxy, halogen, cycloalkyl, haloalkyl, heteroaryl, cycloalkylalkyl, heteroarylalkyl, aralkenyl, alkoxy, aralkoxy, alkoxycarbonyl, arylcarbonyloxy, thio, alkylthio, arylthio, cycloalkylthio, heterocyclylthio, alkylthioalkyl, alkylamino, trialkylsilyl,  
 —OC(O)N(R 8 ) 2 , wherein R 8  is aryl,  
 —SO 2 R 9 , wherein R 9  is aryl,  
 —OP(O)(OR 10 ) 2 , wherein R 10  is alkyl, and  
 —OP(S)(OR 11 ) 2 , wherein R 11  is alkyl; and  
 when R 2  is methyl, R 3  is —CO 2 C 2 H 5 , R 5  is  
                     
 R 6  is methyl, and R 24  is aralkyl, then R 4  is selected from the group consisting of hydroxy, halogen, alkyl, cycloalkyl, haloalkyl, alkenyl, aryl, heteroaryl, cycloalkylalkyl, heteroarylalkyl, aralkenyl, alkoxy, aralkoxy, alkoxycarbonyl, arylcarbonyloxy, thio, alkylthio, arylthio, cycloalkylthio, heterocyclylthio, alkylthioalkyl, alkylamino, trialkylsilyl,  
 —OC(O)N(R 8 ) 2 , wherein R 8  is aryl,  
 —SO 2 R 9 , wherein R 9  is aryl,  
 —OP(O)(OR 10 ) 2 , wherein R 10  is alkyl, and  
 —OP(S)(OR 11 ) 2 , wherein R 11  is alkyl, and  
 when R 2  is methyl, R 3  and R 5  are —CO 2 C 2 H 5 , and R 4  is alkoxy, then R 6  is selected from the group consisting of hydrogen, hydroxy, alkyl comprising at least two carbon atoms, fluorinated alkyl, chlorofluorinated alkyl, alkoxy, alkoxyalkyl, and alkoxycarbonyl,  
 when R 2  is difluoromethyl, R 3  is —CO 2 R 7 , R 4  is alkenyl, R 5  is CO 2 CH 3 , and R 6  is trifluoromethyl, then R 7  is selected from the group consisting of alkyl and cyanoalkyl,  
 when R 2  is methyl, R 4  is hydrogen, R 5  is CO 2 C 2 H 5 , and R 6  is methyl, then R 3  is selected from the group consisting of hydroxy, amido and —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, methyl, alkyl comprising at least three carbon atoms, and cyanoalkyl,  
 when R 2  is difluoromethyl, R 4  is hydrogen, R 5  is CO 2 C 2 H 5 , and R 6  is trifluoromethyl, then R 3  is selected from the group consisting of hydroxy, amido and —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, methyl, alkyl comprising at least three carbon atoms, and cyanoalkyl,  
 when R 2  is difluoromethyl, R 4  is alkylthioalkyl, R 5  is —CO 2 C 2 H 5 , and R 6  is trifluoromethyl, then R 3  is selected from the group consisting of hydroxy, amido and —CO 2 R 7 , wherein R 7  is selected from the group consisting of alkyl and cyanoalkyl,  
 when R 2  is trifluoromethyl, R 3  is —CO 2 CH 3 , R 4  is alkyl, R 5  is —CO 2 CH 3 , then R 6  is selected from the group consisting of hydrogen, hydroxy, alkyl comprising at least two carbon atoms, fluorinated alkyl, chlorofluorinated alkyl, alkoxy, alkoxyalkyl, and alkoxycarbonyl,  
 when R 2  is difluoromethyl, R 4  is alkyl, R 5  is —CO 2 R 14 , R 6  is trifluoromethyl, and R 14  is alkyl, then R 3  is selected from the group consisting of hydroxy and —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, alkyl and cyanoalkyl,  
 when R 2  is selected from the group consisting of hydroxy and trifluoromethyl, R 4  and R 5  are hydrogen, and R 6  is selected from the group consisting of methyl and trifluoromethyl, then R 3  is selected from the group consisting of hydroxy, amido and —CO 2 R 7 , wherein R 7  is selected from the group consisting of alkyl and cyanoalkyl,  
 when R 2  is selected from the group consisting of methyl, difluoromethyl and trifluoromethyl, R 3  is —CO 2 CH 3 , R 5  is hydrogen, and R 6  is selected from the group consisting of methyl and trifluoromethyl, then R 4  is selected from the group consisting of hydrogen, hydroxy, halogen, cycloalkyl, alkenyl, aryl, heteroaryl, cycloalkylalkyl, heteroarylalkyl, aralkenyl, alkoxy, aralkoxy, alkoxycarbonyl, thio, alkylthio, arylthio, cycloalkylthio, heterocyclylthio, alkylthioalkyl, alkylamino, trialkylsilyl,  
 —OC(O)N(R 8 ) 2 , wherein R 8  is aryl,  
 —SO 2 R 9 , wherein R 9  is aryl,  
 —OP(O)(OR 10 ) 2 , wherein R 10  is alkyl; and  
 —OP(S)(OR 11 ) 2 , wherein R 11  is alkyl; and  
 when R 2  is trifluoromethyl, R 3  is —CO 2 C 2 H 5 , R 4  is hydroxy, and R 5  is hydrogen, then R 6  is selected from the group consisting of hydroxy, alkyl, fluorinated alkyl, alkoxy, alkoxyalkyl and alkoxycarbonyl; and  
 when R 2  is trifluoromethyl, R 3  is selected from the group consisting of —CO 2 H and —CO 2 C 2 H 5 , R 5  is methyl, and R 6  is selected from the group consisting of hydrogen and trifluoromethyl, then R 4  is selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, haloalkyl, alkenyl, aryl, heteroaryl, cycloalkylalkyl, heteroarylalkyl, aralkenyl, alkoxy, aralkoxy, alkoxycarbonyl, arylcarbonyloxy, thio, alkylthio, arylthio, cycloalkylthio, heterocyclylthio, alkylthioalkyl, alkylamino, trialkylsilyl,  
 —OC(O)N(R 8 ) 2 , wherein R 8  is aryl,  
 —SO 2 R 9 , wherein R 9  is aryl,  
 —OP(O)(OR 10 ) 2 , wherein R 10  is alkyl, and  
 —OP(S)(OR 11 ) 2 , wherein R 11  is alkyl.  
 
     
     
         4 . The method of  claim 2  wherein: 
 R 2  is selected from the group consisting of methyl and fluorinated methyl; and  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, methyl and ethyl.  
 
     
     
         5 . The method of  claim 2  wherein: 
 R 2  is fluorinated alkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of alkyl, cycloalkyl and cycloalkylalkyl;  
 R 5  is selected from the group consisting of:  
 pyrrolyl;  
                     wherein R 37  and R 38  are independently alkyl;                          wherein R 39  is selected from the group consisting of hydrogen, alkoxy, and alkylthio, and    R 40  is selected from the group consisting of haloalkyl, cycloalkyl, heterocyclylalkoxy, and alkylthio;    
 —N═R 41 , 
 wherein R 41  is heterocyclylidenyl;  
                     
 wherein R 42  is selected from the group consisting of hydrogen and alkyl, and  
 R 43  is selected from the group consisting of cycloalkyl, chlorinated alkyl, and heteroaryl;  
                     
 wherein R 44  is heteroaryl;  
 
 —N═S═O;  
 —N═C═S;  
 —N═C═O; and  
 —N 3 ; and  
 R 6  is fluorinated alkyl;  
 or a pharmaceutically acceptable salt or tautomer thereof.  
 
     
     
         6 . The method of  claim 2  wherein: 
 R 2  is fluorinated alkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, alkoxy and alkylthio;  
 R 5  is selected from the group consisting of:  
 —SR 45 , 
 wherein R 45  is selected from the group consisting of hydrogen, alkyl, haloalkyl, heterocyclyl, aralkyl, heteroaralkyl, aminocarbonylalkyl, alkylthioalkyl,  
 
 —SR 46 , and —CH 2 R 47 , 
 wherein R 46  is selected from the group consisting of aryl and heteroaryl, and  
 R 47  is selected from the group consisting of aryl and heteroaryl; and  
                     
 wherein R 48  is selected from the group consisting of hydrogen and alkyl, and  
 R 49  is selected from the group consisting of alkoxy and haloalkyl;  
                     
 wherein R 50  is selected from the group consisting of alkyl, alkoxy, aryl and heteroaryl;  
                     
 wherein R 51  is selected from the group consisting of alkyl and haloalkyl; and  
                     
 wherein R 53  is aryl; and  
 
 R 6  is fluorinated alkyl;  
 or a pharmaceutically acceptable salt or tautomer thereof.  
 
     
     
         7 . The method of  claim 2  wherein: 
 R 2  is selected from the group consisting of alkyl and fluorinated alkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of hydroxy, alkoxy, aralkoxy, alkoxycarbonyl, alkylthio, arylthio,  
 —OC(O)N(R 8 ) 21  wherein R 8  is aryl,  
 —SO 2 R 9 , wherein R 9  is aryl,  
 —OP(O)(OR 10 ) 2 , wherein R 10  is alkyl, and  
 —OP(S)(OR 11 ) 2 , wherein R 11  is alkyl;  
 R 5  is selected from the group consisting of hydrogen, hydroxy, halogen, alkoxy, and aryloxy; and  
 R 6  is selected from the group consisting of hydrogen, fluorinated alkyl and alkoxycarbonyl;  
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that when R 2  is trifluoromethyl, R 3  is —CO 2 C 2 H 5 , R 4  is hydroxy and R 5  is hydrogen, then R 6  is selected from the group consisting of fluorinated alkyl and alkoxycarbonyl.  
 
     
     
         8 . The method of  claim 2  wherein: 
 R 2  is fluorinated alkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, alkyl and cyanoalkyl;  
 R 4  is selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, arylcarbonyloxy, arylthio, and alkylamino;  
 R 5  is selected from the group consisting of alkyl, haloalkyl, alkynyl, heterocyclyl, heteroaryl, heterocyclylalkyl, arylcarbonyloxyalkyl, alkylthioalkyl, arylthioalkyl, heteroarylthioalkyl, alkoxyalkenyl, cyano,  
                     wherein R 15b  is selected from the group consisting of hydroxy, alkylthio and alkoxy, and    R 16b  is selected from the group consisting of alkyl and heteroaryl;                          wherein R 17  and R 18  are each alkyl;                          wherein R 19  is selected from the group consisting of heteroaryl, —SR 20 , —OR 21 , and —R 22 CO 2 R 23 , wherein R 20  is selected from the group consisting of alkyl, aryl and aminoalkyl,    R 21  is aryl,    R 22  is alkylene, and    R 23  is alkyl;                          wherein R 24  is selected from the group consisting of hydrogen, unsubstituted alkyl, and aralkyl;                          wherein R 25  is heterocyclylidenyl;                          wherein R 26  and R 27  are independently alkyl;                          wherein R 28  and R 29  are independently alkyl;                          wherein R 30  and R 31  are each alkoxy;                          wherein R 32  is selected from the group consisting of hydrogen and alkyl, and    
 R 33  is alkyl;  
                     
 and  
 —C≡C—Si(R 36 ) 3 , 
 wherein R 36  is alkyl; and  
 
 R 6  is selected from the group consisting of hydrogen, fluorinated alkyl and alkoxy,  
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that:  
 when R 2  is difluoromethyl, R 3  is —CO 2 CH 3 , R 5  is  
                     
 R 6  is trifluoromethyl, and R 19  is the heteroaryl 1-pyrazolyl, then R 4  is selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, arylcarbonyloxy, and arylthio; and  
 when R 2  is difluoromethyl, R 3  is —CO 2 CH 3 , R 5  is the heterocyclyl 2-(4,5-dihydro-oxazolyl), and R 6  is trifluoromethyl, then R 4  is selected from the group consisting of alkyl, alkoxy, cycloalkyl, arylcarbonyloxy, arylthio, and alkylamino; and  
 when R 2  and R 6  are independently fluorinated methyl, R 3  is —CO 2 R 7 , R 5  is cyano, and R 7  is selected from the group consisting of hydrogen and alkyl, then R 4  is selected from the group consisting of alkoxy, cycloalkyl, cycloalkylalkyl, arylcarbonyloxy, arylthio, and alkylamino.  
 
     
     
         9 . The method of  claim 2  wherein: 
 R 2  is selected from the group consisting of hydroxy, alkyl, fluorinated alkyl, and alkoxyalkyl;  
 R 3  is selected from the group consisting of hydroxy, amido, and —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, cycloalkyl, haloalkyl, alkenyl, aryl, heteroaryl, heteroarylalkyl, alkoxy, alkoxycarbonyl, aralkenyl, thio, alkylthio, cycloalkylthio, heterocyclylthio, alkylthioalkyl, and trialkylsilyl;  
 R 5  is CO 2 R 14 , wherein R 14  is alkyl;  
 R 6  is selected from the group consisting of hydrogen, hydroxy, alkyl, fluorinated alkyl, and alkoxyalkyl,  
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that,  
 when R 2  is methyl, R 3  is —CO 2 C 2 H 5 , R 4  is alkoxy, and R 5  is —CO 2 C 2 H 5 , then R 6  is selected from the group consisting of hydrogen, hydroxy, alkyl comprising at least two carbon atoms, fluorinated alkyl, and alkoxyalkyl,  
 when R 2  is difluoromethyl, R 3  is —CO 2 R 7 , R 4  is alkenyl, R 5  is CO 2 CH 3 , and R 6  is trifluoromethyl, R 7  is alkyl,  
 when R 2  is methyl, R 4  is hydrogen, R 5  is CO 2 R 14 , R 6  is methyl, and R 14  is alkyl, R 3  is selected from the group consisting of hydroxy, amido and —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, methyl, alkyl comprising at least three carbon atoms and cyanoalkyl,  
 when R 2  is difluoromethyl, R 4  is hydrogen, R 5  is CO 2 R 14 , R 6  is trifluoromethyl, and R 14  is alkyl, R 3  is selected from the group consisting of hydroxy, amido and —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, methyl, alkyl comprising at least three carbon atoms and cyanoalkyl,  
 when R 2  is difluoromethyl, R 4  is alkylthioalkyl, R 5  is CO 2 C 2 H 5 , and R 6  is methyl, R 3  is selected from the group consisting of hydroxy, amido and —CO 2 R 7 , wherein R 7  is alkyl, and  
 when R 2  is trifluoromethyl, R 3  is —CO 2 CH 3 , R 4  is alkyl, and R 5  is —CO 2 CH 3 , R 6  is selected from the group consisting of hydrogen, hydroxy, alkyl comprising two or more carbon atoms, fluorinated alkyl, and alkoxyalkyl; and  
 when R 2  is difluoromethyl, R 4  is alkyl, R 5  is selected from the group consisting of —CO 2 CH 3  and —CO 2 C 2 H 5 , and R 6  is trifluoromethyl, R 3  is selected from the group consisting of hydroxy and —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl.  
 
     
     
         10 . The method of  claim 2  wherein the compound of formula IA is selected from the compounds and pharmaceutically acceptable salts and tautomers thereof of the group consisting of: 
 Methyl 5-[(4-t-Butylphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl))-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(palmitoylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-(methoxycarbonylthio)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Diethyl 2,6-Bis(trifluoromethyl)-4-(trimethylsilyl)-3,5-pyridinedicarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(methylthiomethylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-(1-Bromo-2-methoxyethenyl)-4-(cyclopropylmethyl)-2-(difluoromethyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-(Chloroethylthio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 4-(i-Propoxy)-5-{[3-(methoxycarbonyl)-4-(1-propoxy-)-6-(trifluoromethyl)-5-pyridyl]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-cyclobutyl-5-(1-pyrrolyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(aminothionocarbonyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(dimethylamino)carbonyl]thiomethyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-[(diethylphosphono) carbonyl]-4-(i-propylamino)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Dimethyl 2,6-Bis(methoxymethyl)-4-propyl-3,5-pyridinecarboxylate;  
 Methyl 5-[(Aminocarbonyl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-(1-ethoxyethylthio)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(1-methoxyethylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-(2-fluoroethylthio) 4 -(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-(Acetylthio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(2-tetrhydrofurylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-{[(3,5-di-t-butylphenyl) thio]carbonyl}-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-{[(2,4-dimethylphenyl) thio]carbonyl}-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-methoxyphenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(3-methoxyphenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-{[(2,4-di-t-butylphenyl) thio]carbonyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[(4-t-Butylphenyl)thio]carbonyl}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-isopropylphenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-([(3,5-dimethylphenyl) thio]carbonyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(4-methylthiophenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-(4-fluorobenzyl)-4-isopropylphenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-(4-fluorobenzyl)-4-fluorophenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[(4-chlorophenyl)thio]carbonyl}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-([(2,5-Dichlorophenyl)thio]carbonyl}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[(2,6-Dichlorophenyl)thio]carbonyl}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-naphthyl)thio]carbonyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(1-naphthyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 3-Methyl 5-(3-Methoxyphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2-Nitrophenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(3,5-Di-t-butylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2,4-Di-t-butylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(4-t-Butylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-[2-(4-Fluorobenzyl)-4-isopropylphenyl]2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-[2-(4-Fluorobenzyl)-3,4,5-(trimethoxy) phenyl]2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2-Methoxyphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(4-Chlorophenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(3,5-Dimethylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2-Isopropylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2,6-Dimethyl-4-nitrophenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2,4-Dimethylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 Methyl 5-(4-t-Butylphenyldithio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Dimethyl 5,5′-Dithiobis[2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-([2-(Difluoromethyl)-4-(2-methylpropyl)-3-(methoxycarbonyl)-6-(trifluoromethyl)-5-pyridyl]methylthio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-([2-(Difluoromethyl)-4-(2-methylpropyl)-3-(methoxycarbonyl)-6-(trifluoromethyl)-5-pyridyl]carbonylthio}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Bromophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Chlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,3,5,6-Tetrafluorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3,5-Di-t-butylphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(1-Methylimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(1-Methyltetrazol-5-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(5-Nitrobenzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-(Trifluoromethoxy)phenyl))thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Quinolin-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Bromophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Pentafluorophenyl)thiomethyl]-2-(difluoro-methyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,5-Dichlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,3,5,6-Tetrafluoro-4-(trifluoromethyl) phenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Methylpyrimidin-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Nitrophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Methoxyphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-Chlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,6-Dichlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Quinolin-8-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Pyrimidin-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-(Acetylamino)phenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzoxazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Bromo-2-(trifluoromethoxy)phenyl) thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Aminophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-Methoxyphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(5-Methylbenzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Methoxyphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzothiazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Chlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3,4-Dichlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-Naphthyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-Pyridyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-bromophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Bis{3-(carbomethoxy)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-5-pyridyl]methyl Sulfide;  
 Methyl 5-[(2-Chloro-3,4-methylenedioxyphenyl) methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-pyridyl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-quinolinyl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-naphthyl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate; and  
 Methyl 5[(6-chloro-1,3-benzodioxan-8-yl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Diethyl 5,5′-(Carbonyldiimino)bis[6(difluoromethyl)-4-ethyl-2-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(dimethylamino)thiono]thiomethyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-phenyl-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]hydroxymethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-phenyl-6-(trifluoromethyl)-3-([4-(trifluoromethyl)phenyl]carbonyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]hydroxymethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]carbonyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]fluoromethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]fluoromethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-(2-naphthylfluoromethyl)pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]mercaptomethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-phenyl-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]mercaptomethyl}pyridine;  
 2-(Cyclopentyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]carbonyl}pyridine;  
 2-(1-Pyrrolidinyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-([4-(trifluoromethyl)phenyl]carbonyl}pyridine;  
 2-(1-Pyrrolidinyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]hydroxymethyl}pyridine; and  
 2-(1-Pyrrolidinyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]fluoromethyl}pyridine.  
 
     
     
         11 . The method of  claim 2  wherein 
 R 2  is selected from the group consisting of alkyl and fluorinated alkyl;  
 R 3  is selected from the group consisting of —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of alkyl, cycloalkyl, arylcarbonyloxy, thio, arylthio, and heterocyclylthio,  
 R 5  is selected from the group consisting of alkyl, heterocyclyl, arylthioalkyl, heteroarylthioalkyl,  
 —CO 2 R 14 , 
 wherein R 14  is alkyl;  
                     
 wherein R 15b  is hydroxy, and  
 R 16b  is heteroaryl;  
                     
 wherein R 19  is —SR 20 , and R 20  is alkyl;  
                     
 wherein R 39  is alkoxy, and  
 R 40  is haloalkyl;  
 
 —N═R 41 , 
 wherein R 41  is heterocyclylidenyl;  
 
 —N═S═O;  
 —SR 45 , 
 wherein R 45  is selected from the group consisting of hydrogen, —SR 46 , and —CH 2 R 47 ,  
 wherein R 46  is selected from the group consisting of aryl and heteroaryl, and  
 R 47  is selected from the group consisting of aryl and heteroaryl; and  
                     
 wherein R 50  is selected from the group consisting of alkyl and alkoxy;  
 
 R 6  is selected from the group consisting of alkyl and fluorinated alkyl.  
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that when R 2  is trifluoromethyl, R 3  is CO 2 CH 3 , R 4  is isobutyl, and R 5  is —CO 2 CH 3 , then R 6  is selected from the group consisting of alkyl comprising at least two carbon atoms and fluorinated alkyl.  
 
     
     
         12 . The method of  claim 2  wherein the compound of formula IA is selected from the compounds and pharmaceutically acceptable salts and tautomers thereof of the group consisting of: 
 Methyl 5-(4-t-Butylphenyldithio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Dimethyl 5,5′-Dithiobis[2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3,4-Dichlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-isothiocyanato-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-Naphthyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-mercapto-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 5-Ethyl 3-Methyl 2-(Difluoromethyl)-4-[(4,5-dihydro-2-thiazolyl)thio]-6-(trifluoromethyl)-3,5-pyridinedicarboxylate;  
 Methyl 5-[(4-Nitrophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(palmitoylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-(methoxycarbonylthio)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-t-Butylphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl))-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-[(1,4-dithian-2-ylidene) amino]-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-(Trifluoromethoxy)phenyl))thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Chlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(5-Methylbenzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzothiazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Chlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[3-(Carbomethoxy)-2-(difluoromethyl)-4-isobutyl-6-(trifluoromethyl)-5-pyridyl]thiomethyl}-2-(difluoromethyl)-4-isobutyl-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Di-t-Butyl 2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridinedicarboxylate;  
 Methyl 5-[(4-Bromophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,3,5,6-Tetrafluoro-4-(trifluoromethyl) phenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Methoxyphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzoxazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(4,5-dihydro-2-thiazoyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Ethyl 2,6-Bis(trifluoromethyl)-5-methyl-4-[4-(trifluoromethylphenyl)carbonyloxy]-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-[(i-propylthio)carbonyl]-4-(cyclobutyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 4-(4-i-Propylphenylthio)-5-methyl-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(5-Nitrobenzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate; and  
 Bis {[3-(carbomethoxy)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-5-pyridyl]methyl Sulfide.  
 
     
     
         13 . The method of  claim 2  wherein the compound of formula IA is Dimethyl 5,5′-dithiobis[2-difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate].  
     
     
         14 . A compound represented by the generic formula:  
       
         
           
           
               
               
           
         
         wherein:  
         R 2  and R 6  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, fluorinated alkyl, fluorinated aralkyl, chlorofluorinated alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, alkoxyalkyl, and alkoxycarbonyl; provided that at least one of R 2  and R 6  is fluorinated alkyl, chlorofluorinated alkyl or alkoxyalkyl;  
         R 3  is selected from the group consisting of arylcarbonyl, heteroarylcarbonyl, hydroxymethyl, arylalkoxyalkyl, trialkylsilyloxyalkyl,  
         —CHO,  
         —CO 2 R 7 , 
 wherein R 7  is selected from the group consisting of hydrogen and alkyl; and  
                     
 wherein R 15a  is selected from the group consisting of hydroxy, halogen, alkylthio and alkoxy, and  
 R 16a  is selected from the group consisting of alkyl, haloalkyl, alkenyl, aryl and heteroaryl;  
 
         R 4  is selected from the group consisting of hydrogen, hydroxy, alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroarylalkyl, alkoxy, thio, trialkylsilyl, alkylamino, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl;  
         R 5  is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aralkyl, alkoxy, aryloxy, cycloalkylthioalkyl, arylthioalkyl, heteroarylthioalkyl, alkoxyalkenyl, arylcarbonyloxyalkyl, pyrrolyl, substituted pyrrolidinyl, hydroxymethyl, arylalkoxyalkyl, and trialkylsilyloxyalkyl,  
         CO 2 R 14 , 
 wherein R 14  is alkyl;  
                     
 wherein R 15b  is selected from the group consisting of hydroxy, halogen, alkoxy, and alkylthio, aroyloxy, and alkylsulfonyloxy, and  
 R 16b  is selected from the group consisting of alkyl, alkenyl, aryl, and heteroaryl;  
                     
 wherein R 17  and R 18  are independently alkyl;  
                     
 wherein R 19  is aryl, heteroaryl, —SR 20 , and —OR 21 ,  
 wherein R 20  is selected from the group consisting of aryl, heteroaryl and aminoalkyl, and  
 R 21  is selected from the group consisting of aryl and heteroaryl;  
                     
 wherein R 24  is aralkyl;  
                     
 wherein R 28  and R 29  are independently alkyl;  
                     
 wherein R 30  and R 31  are independently alkoxy;  
 
         —C≡C—Si(R 36 ) 3 , 
 wherein R 36  is alkyl;  
                     
 wherein R 37  is selected from the group consisting of hydrogen, alkoxy, and alkylthio, and  
 R 38  is selected from the group consisting of haloalkyl, cycloalkyl, heterocyclylalkoxy, and alkylthio;  
 provided that when R 37  is hydrogen, then R 38  is selected from the group consisting of haloalkyl, cycloalkyl, and heterocyclylalkoxy;  
                     
 wherein R 42  is selected from the group consisting of hydrogen and alkyl, and  
 R 43  is substituted heteroaryl;  
                     
 wherein R 44  is selected from the group consisting of aryl and heteroaryl;  
 
         —SR 45 , 
 wherein R 45  is selected from the group consisting of haloalkyl, heterocyclyl, alkylthioalkyl, aminocarbonylalkyl, —SR 46 , and —CH 2 R 47 ,  
 wherein R 46  is selected from the group consisting of aryl and heteroaryl, and  
 R 47  is selected from the group consisting of methylenedioxyphenyl, pyridyl, quinolinyl, tetrahydronaphthyl and benzodioxanyl;  
                     
 wherein R 48  is selected from the group consisting of hydrogen and alkyl, and  
 R 49  is selected from the group consisting of alkoxy and haloalkyl;  
                     
 wherein R 50  is selected from the group consisting of alkyl, alkoxy, and heteroaryl; and  
                     
 wherein R 51  is haloalkyl;  
 
         or a pharmaceutically acceptable salt or tautomer thereof,  
         provided that:  
         when R 2  is selected from the group consisting of difluoromethyl and trifluoromethyl, R 3  is selected from the group consisting of —CO 2 H, —CO 2 CH 3  and —CO 2 C 2 H 5 , R 5  is hydrogen, and R 6  is selected from the group consisting of hydrogen and trifluoromethyl, then R 4  is selected from the group consisting of cycloalkyl, cycloalkylalkyl, heteroarylalkyl, aralkenyl, alkoxy, thio, trialkylsilyl, alkylamino, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl; provided further that when R 2 , R 3  and R 5  are as defined above, and R 4  is alkoxy, then R 6  is hydrogen;  
         when R 2  is selected from the group consisting of fluorinated methyl and chlorofluorinated methyl, R 3  is selected from the group consisting of hydroxymethyl and CO 2 R 7 , R 5  is selected from the group consisting of hydroxymethyl and CO 2 R 14 , R 6  is selected from the group consisting of fluorinated methyl and chlorofluorinated methyl, and R 7  and R 14  are independently alkyl, then R 4  is selected from the group consisting of thio, trialkylsilyl, and —OC(O)N(R 8 ) 21  wherein R 8  is aryl;  
         when R 2  is difluoromethyl, R 3  is —CO 2 C 2 H 5 , R 4  is hydrogen, R 5  is —CO 2 C 2 H 5 , then R 6  is selected from the group consisting of hydrogen, monofluoroalkyl, difluoroalkyl and alkoxyalkyl;  
         when R 2  is trifluoromethyl, R 3  is —CO 2 R 7 , R 5  is methyl, R 6  is selected from the group consisting of fluorinated methyl, fluorinated ethyl and chlorofluorinated methyl, and R 7  is selected from the group consisting of hydrogen and alkyl, then R 4  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heteroarylalkyl, thio, trialkylsilyl, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl;  
         when R 4  is selected from the group consisting of alkyl, cycloalkyl and cycloalkylalkyl, R 3  is —CO 2 R 7 , and R 7  is alkyl, then R 5  is other than arylcarbonyl, heteroarylcarbonyl or  
         
           
             
             
                 
                 
             
           
         
         wherein R 16b  is alkyl when R 15b  is selected from the group consisting of hydroxy, halogen, alkylthio and alkoxy, or wherein R 16b  is aryl or heteroaryl when R 15b  is hydroxy;  
         when R 4  is selected from the group consisting of alkyl, cycloalkyl and cycloalkylalkyl, R 5  is —CO 2 R 14 , and R 14  is alkyl, then R 3  is other than arylcarbonyl, heteroarylcarbonyl or  
         
           
             
             
                 
                 
             
           
         
         wherein R 16a  is alkyl when R 15a  is selected from the group consisting of hydroxy, halogen, alkylthio and alkoxy, or wherein R 16a  is aryl or heteroaryl when R 15a  is hydroxy; and  
         when R 2  and R 6  are independently selected from fluorinated methyl and chlorofluorinated methyl, R 3  is CO 2 R 7 , R 5  is hydroxy, alkoxy or aryloxy, then R 4  is selected from the group consisting of aryl, cycloalkyl, cycloalkylalkyl, heteroarylalkyl, thio, trialkylsilyl, alkylamino, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl; and  
         when R 4  is aryl and one of R 2  and R 6  is trifluoromethyl, then the other of R 2  and R 6  is difluoromethyl.  
       
     
     
         15 . A compound of  claim 14  wherein: 
 R 2  is fluorinated methyl; and  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, methyl and ethyl.  
 
     
     
         16 . A compound of  claim 14  wherein: 
 R 2  is fluorinated alkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of alkyl and cycloalkyl;  
 R 5  is selected from the group consisting of:  
 1-pyrrolyl;  
                     wherein R 37  is selected from the group consisting of hydrogen, alkoxy, and alkylthio, and    R 38  is selected from the group consisting of haloalkyl, cycloalkyl, heterocyclylalkoxy, and alkylthio;    provided that when R 37  is hydrogen, then R 38  is selected from the group consisting of haloalkyl, cycloalkyl, and heterocyclylalkoxy;                          wherein R 42  is selected from the group consisting of hydrogen and alkyl, and    R 43  is substituted heteroaryl;                          wherein R 44  is pyridyl; and    
 R 6  is fluorinated alkyl;  
 or a pharmaceutically acceptable salt or tautomer thereof.  
 
     
     
         17 . A compound of  claim 14  wherein: 
 R 2  is fluorinated alkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is alkyl;  
 R 5  is selected from the group consisting of:  
 —SR 45  
 wherein R 45  is selected from the group consisting of haloalkyl, heterocyclyl, aralkyl, heteroaralkyl, alkylthioalkyl, aminocarbonylalkyl, —SR 46 , and —CH 2 R 47 ,  
 wherein R 46  is selected from the group consisting of aryl and heteroaryl, and  
 R 47  is selected from the group consisting of methylenedioxyphenyl, pyridyl, quinolinyl, tetrahydronaphthyl and benzodioxanyl; and  
                     
 wherein R 48  is selected from the group consisting of hydrogen and alkyl, and  
 R 49  is selected from the group consisting of alkoxy and haloalkyl;  
                     
 wherein R 50  is selected from the group consisting of alkyl, alkoxy, and heteroaryl;  
                     
 wherein R 51  is haloalkyl; and  
 
 R 6  is fluorinated alkyl;  
 or a pharmaceutically acceptable salt or tautomer thereof.  
 
     
     
         18 . A compound of  claim 14  wherein: 
 R 2  is fluorinated alkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is hydroxy, alkoxy, —OC(O)N(R 8 ) 21  or —OP(O) (OR 10 ) 2 , wherein R 8  is aryl and R 10  is alkyl;  
 R 5  is selected from the group consisting of hydrogen, alkoxy and aryloxy; and  
 R 6  is selected from the group consisting of hydrogen and fluorinated alkyl;  
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that when R 2  is trifluoromethyl, R 3  is selected from the group consisting of —CO 2 CH 3  and —CO 2 C 2 H 5 , R 5  is hydrogen, and R 6  is selected from the group consisting of hydrogen and trifluoromethyl, then R 4  is selected from the group consisting of alkoxy, —OC(O)N(R 8 ) 2 , or —OP(O) (OR 10 ) 2 , wherein R 8  is aryl and R 10  is alkyl; provided further that when R 2 , R 3  and R 5  are as defined above, and R 4  is alkoxy, then R 6  is hydrogen.  
 
     
     
         19 . A compound of  claim 14  wherein: 
 R 2  is fluorinated alkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, arylthio, and alkylamino; and  
 R 5  is selected from the group consisting of alkyl, arylcarbonyloxyalkyl, arylthioalkyl, heteroarylthioalkyl, alkoxyalkenyl, substituted pyrrolidinyl,  
                     wherein R 15b  is alkoxy, and R 16b  is heteroaryl;                          wherein R 17  and R 18  are independently alkyl;                          wherein R 19  is selected from the group consisting of pyridyl, —SR 20 , and —OR 21 , wherein R 20  is selected from the group consisting of aryl, heteroaryl and aminoalkyl, and R 21  is selected from the group consisting of aryl and heteroaryl;                          wherein R 24  is aralkyl;                          wherein R 26  and R 27  are independently alkyl;                          wherein R 28  and R 29  are independently alkoxy; and    
 —C≡C—Si(R 10 ) 3 , 
 wherein R 10  is alkyl; and  
 
 R 6  is selected from the group consisting of hydrogen and fluorinated alkyl,  
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that:  
 when R 2  is trifluoromethyl, R 3  is —CO 2 C 2 H 5 , R 4  is iso-propoxy, R 5  is methyl, then R 6  is hydrogen; and  
 when R 5  is alkyl, then R 4  is selected from the group consisting of cycloalkyl, cycloalkylalkyl, arylthio, and alkylamino.  
 
     
     
         20 . A compound of  claim 14  wherein: 
 R 2  is selected from the group consisting of fluorinated alkyl and alkoxyalkyl;  
 R 3  is —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of hydrogen, hydroxy, alkyl, heteroarylalkyl, thio, and trialkylsilyl;  
 R 5  is CO 2 R 14 , wherein R 14  is alkyl; and  
 R 6  is selected from the group consisting of hydrogen, fluorinated alkyl, and alkoxyalkyl,  
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that when R 2  is difluoromethyl, R 3  is —CO 2 C 2 H 5 , R 4  is hydrogen, R 5  is CO 2 C 2 H 5 , then R 6  is selected from the group consisting of hydrogen, monofluoroalkyl, and difluoroalkyl.  
 
     
     
         21 . A compound of  claim 14  selected from compounds and their pharmaceutically acceptable salts and tautomers of the group consisting of: 
 Methyl 5-[(4-t-Butylphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl))-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(palmitoylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-(methoxycarbonylthio)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Diethyl 2,6-Bis(trifluoromethyl)-4-(trimethylsilyl)-3,5-pyridinedicarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(methylthiomethylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-(1-Bromo-2-methoxyethenyl)-4-(cyclopropylmethyl)-2-(difluoromethyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-(Chloroethylthio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 4-(i-Propoxy)-5-{[3-(methoxycarbonyl)-4-(1-propoxy-)-6-(trifluoromethyl)-5-pyridyl]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-cyclobutyl-5-(1-pyrrolyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(aminothionocarbonyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(dimethylamino)carbonyl]thiomethyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-[(diethylphosphono) carbonyl]-4-(i-propylamino)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Dimethyl 2,6-Bis(methoxymethyl)-4-propyl-3,5-pyridinecarboxylate;  
 Methyl 5-[(Aminocarbonyl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-(1-ethoxyethylthio)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(1-methoxyethylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-(2-fluoroethylthio) 4 -(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-(Acetylthio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-(2-tetrhydrofurylthio)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-([(3,5-di-t-butylphenyl) thio]carbonyl}-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-{[(2,4-dimethylphenyl) thio]carbonyl}-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-methoxyphenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-0.5-{[(3-methoxyphenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-{[(2,4-di-t-butylphenyl) thio]carbonyl}-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[(4-t-Butylphenyl)thio]carbonyl}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-isopropylphenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-5-{[(3,5-dimethylphenyl) thio]carbonyl}-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(4-methylthiophenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-(4-fluorobenzyl)-4-isopropylphenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-(4-fluorobenzyl)-4-fluorophenyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[(4-chlorophenyl)thio]carbonyl}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[(2,5-Dichlorophenyl)thio]carbonyl}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[(2,6-Dichlorophenyl)thio]carbonyl}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(2-naphthyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(1-naphthyl)thio]carbonyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 3-Methyl 5-(3-Methoxyphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2-Nitrophenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(3,5-Di-t-butylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2,4-Di-t-butylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(4-t-Butylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-[2-(4-Fluorobenzyl)-4-isopropylphenyl]2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-[2-(4-Fluorobenzyl)-3,4,5-(trimethoxy) phenyl]2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2-Methoxyphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(4-Chlorophenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(3,5-Dimethylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2-Isopropylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2,6-Dimethyl-4-nitrophenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 3-Methyl 5-(2,4-Dimethylphenyl) 2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3,5-pyridicarboxylate;  
 Methyl 5-(4-t-Butylphenyldithio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Dimethyl 5,5′-Dithiobis[2-(Difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[2-(Difluoromethyl)-4-(2-methylpropyl)-3-(methoxycarbonyl)-6-(trifluoromethyl)-5-pyridyl]methylthio)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-{[2-(Difluoromethyl)-4-(2-methylpropyl)-3-(methoxycarbonyl)-6-(trifluoromethyl)-5-pyridyl]carbonylthio}-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Bromophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Chlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,3,5,6-Tetrafluorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3,5-Di-t-butylphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(1-Methylimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(1-Methyltetrazol-5-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(5-Nitrobenzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-(Trifluoromethoxy)phenyl))thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Quinolin-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Bromophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Pentafluorophenyl)thiomethyl]-2-(difluoro-methyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,5-Dichlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,3,5,6-Tetrafluoro-4-(trifluoromethyl) phenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Methylpyrimidin-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Nitrophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Methoxyphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-Chlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2,6-Dichlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Quinolin-8-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Pyrimidin-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-(Acetylamino)phenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzoxazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(4-Bromo-2-(trifluoromethoxy)phenyl) thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Aminophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-Methoxyphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(5-Methylbenzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzimidazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Methoxyphenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(Benzothiazol-2-yl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3-Chlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(3,4-Dichlorophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-((2-Naphthyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-Pyridyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-bromophenyl)thiomethyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Bis{3-(carbomethoxy)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-5-pyridyl]methyl Sulfide;  
 Methyl 5-[(2-Chloro-3,4-methylenedioxyphenyl) methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-pyridyl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(2-quinolinyl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 5-[(1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-naphthyl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate; and  
 Methyl 5[(6-chloro-1,3-benzodioxan-8-yl)methylthio]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 Diethyl 5,5′-(Carbonyldiimino)bis[6(difluoromethyl)-4-ethyl-2-(trifluoromethyl)-3-pyridinecarboxylate;  
 Methyl 2-(Difluoromethyl)-4-(2-methylpropyl)-5-{[(dimethylamino)thiono]thiomethyl}-6-(trifluoromethyl)-3-pyridinecarboxylate;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-phenyl-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]hydroxymethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-phenyl-6-(trifluoromethyl)-3-([4-(trifluoromethyl)phenyl]carbonyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]hydroxymethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]carbonyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]fluoromethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]fluoromethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-(2-naphthylfluoromethyl)pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]mercaptomethyl}pyridine;  
 2-(Difluoromethyl)-5-hydroxymethyl-4-phenyl-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]mercaptomethyl}pyridine;  
 2-(Cyclopentyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]carbonyl}pyridine;  
 2-(1-Pyrrolidinyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]carbonyl}pyridine;  
 2-(1-Pyrrolidinyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]hydroxymethyl}pyridine; and  
 2-(1-Pyrrolidinyl)-5-hydroxymethyl-4-(4-fluorophenyl)-6-(trifluoromethyl)-3-{[4-(trifluoromethyl)phenyl]fluoromethyl}pyridine.  
 
     
     
         22 . The compound of  claim 14  wherein 
 R 2  is selected from the group consisting of alkyl and fluorinated alkyl;  
 R 3  is selected from the group consisting of —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen and alkyl;  
 R 4  is selected from the group consisting of alkyl and thio;  
 R 5  is selected from the group consisting of heterocyclyl, arylthioalkyl, heteroarylthioalkyl,  
 —CO 2 R 14 , 
 wherein R 14  is alkyl;  
                     
 wherein R 39  is alkoxy, and  
 R 40  is haloalkyl;  
 
 —SR 45 , 
 wherein R 45  is selected from the group consisting of hydrogen, —SR 46 , and —CH 2 R 47 ,  
 wherein R 46  is selected from the group consisting of aryl and heteroaryl, and  
 R 47  is selected from the group consisting of methylenedioxyphenyl, pyridyl, quinolinyl, naphthyl and benzodioxanyl; and  
                     
 wherein R 50  is selected from the group consisting of alkyl and alkoxy; and  
 
 R 6  is selected from the group consisting of alkyl and fluorinated alkyl;  
 or a pharmaceutically acceptable salt or tautomer thereof,  
 provided that when R 2  is trifluoromethyl, R 3  is CO 2 CH 3 , R 4  is isobutyl, and R 5  is CO 2 CH 3 , then R 6  is selected from the group consisting of alkyl comprising at least two carbon atoms and fluorinated alkyl.  
 
     
     
         23 . A compound of  claim 14  that is Dimethyl 5,5′-dithiobis[2-difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate].  
     
     
         24 . A pharmaceutical composition for the prophylaxis or treatment of a hyperlipidemic condition wherein the condition is atherosclerosis and the composition comprises an atherosclerotic amount of a compound of Formula IA of  claim 1  with a pharmaceutically acceptable carrier.  
     
     
         25 . A pharmaceutical composition for the prophylaxis or treatment of a hyperlipidemic condition wherein the condition is dislipidemia and the composition comprises a therapeutically effective amount of a compound of Formula IA of  claim 1  with a pharmaceutically acceptable carrier.  
     
     
         26 . A method for inhibiting the activity of cholesteryl ester transfer protein in vivo by administering to a subject a therapeutically effective amount of a compound of Formula IB:  
       
         
           
           
               
               
           
         
         wherein:  
         R 2  and R 6  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, fluorinated alkyl, fluorinated aralkyl, chlorofluorinated alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, alkoxyalkyl, and alkoxycarbonyl; provided that at least one of R 2  and R 6  is fluorinated alkyl, chlorofluorinated alkyl or alkoxyalkyl;  
         R 3  is selected from the group consisting of hydroxy, amido, arylcarbonyl, heteroarylcarbonyl, hydroxymethyl  
         —CHO,  
         —CO 2 R 7 , wherein R 7  is selected from the group consisting of hydrogen, alkyl and cyanoalkyl; and  
         
           
             
             
                 
                 
             
           
           wherein R 15a  is selected from the group consisting of hydroxy, hydrogen, halogen, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy and heterocyclyloxy, and  
           R 16a  is selected from the group consisting of alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, and heterocyclyl, arylalkoxy, trialkylsilyloxy;  
         
         R 4  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, heteroarylalkenyl, heterocyclylalkenyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkanoyloxy, alkenoyloxy, alkynoyloxy, aryloyloxy, heteroaroyloxy, heterocyclyloyloxy, alkoxycarbonyl, alkenoxycarbonyl, alkynoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heterocyclyloxycarbonyl, thio, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, alkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclylthioalkenyl, alkylamino, alkenylamino, alkynylamino, arylamino, heteroarylamino, heterocyclylamino, aryldialkylamino, diarylamino, diheteroarylamino, alkylarylamino, alkylheteroarylamino, arylheteroarylamino, trialkylsilyl, trialkenylsilyl, triarylsilyl, 
 —OC(O)N(R 8a R 8b ), wherein R 8a  and R 8b  are independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl,  
 —SO 2 R 9 , wherein R 9  is selected from the group consisting of hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl,  
 —OP(O)(OR 10a ) (OR 10b ), wherein R 10 , and R 10b  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and  
 —OP(S)(OR 11a ) (OR 11b ), wherein R 11a  and R 11b  are independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
 
         R 5  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkylcarbonyloxyalkyl, alkenylcarbonyloxyalkyl, alkynylcarbonyloxyalkyl, arylcarbonyloxyalkyl, heteroarylcarbonyloxyalkyl, heterocyclylcarbonyloxyalkyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, heteroarylalkenyl, heterocyclylalkenyl, alkylthioalkyl, cycloalkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclylthioalkenyl, alkoxyalkyl, alkenoxyalkyl, alkynoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, heterocyclyloxyalkyl, alkoxyalkenyl, alkenoxyalkenyl, alkynoxyalkenyl, aryloxyalkenyl, heteroaryloxyalkenyl, heterocyclyloxyalkenyl, cyano, hydroxymethyl,  
         —C 2 R 14 , 
 wherein R 14  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
                     
 wherein R 15b  is selected from the group consisting of hydroxy, hydrogen, halogen, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, aroyloxy, and alkylsulfonyloxy, and  
 R 16b  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, arylalkoxy, and trialkylsilyloxy;  
                     
 wherein R 17  and R 18  are independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
                     
 wherein R 19  is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, —SR 20 , —OR 21 , and —R 22 CO 2 R 23 , wherein  
 R 20  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aminoaryl, aminoheteroaryl, aminoheterocyclyl, alkylheteroarylamino, arylheteroarylamino,  
 R 21  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl,  
 R 22  is selected from the group consisting of alkylene or arylene, and  
 R 23  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 wherein R 24  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, aralkyl, aralkenyl, and aralkynyl;  
                     
 wherein R 25  is heterocyclylidenyl;  
                     
 wherein R 26  and R 27  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 wherein R 28  and R 29  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 wherein R 30  and R 31  are independently alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, and heterocyclyloxy; and  
                     
 wherein R 32  and R 33  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 
         —C≡C—Si(R 36 ) 3 , 
 wherein R 36  is selected from the group consisting of alkyl, alkenyl, aryl, heteroaryl and heterocyclyl;  
                     
 wherein R 37  and R 38  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                     
 wherein R 39  is selected from the group consisting of hydrogen, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio and heterocyclylthio, and  
 R 40  is selected from the group consisting of haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, haloheterocyclyl, cycloalkyl, cycloalkenyl, heterocyclylalkoxy, heterocyclylalkenoxy, heterocyclylalkynoxy, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio and heterocyclylthio;  
 
         —N═R 41 , 
 wherein R 41  is heterocyclylidenyl;  
                     
 wherein R 42  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl, and  
 R 43  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, and haloheterocyclyl;  
                     
 wherein R 44  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
 
         —N═S═O;  
         —N═C═S;  
         —N═C═O;  
         —N 3 ;  
         —SR 45 , &lt;wherein R 45  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, haloheterocyclyl, heterocyclyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, heteroarylalkenyl, heterocyclylalkenyl, alkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclylthioalkenyl, aminocarbonylalkyl, aminocarbonylalkenyl, aminocarbonylalkynyl, aminocarbonylaryl, aminocarbonylheteroaryl, and aminocarbonylheterocyclyl,  
         —SR 46 , and —CH 2 R 47 , 
 wherein R 46  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and  
 R 47  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl; and  
                     
 wherein R 48  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and  
 R 49  is selected from the group consisting of alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl and haloheterocyclyl;  
                     
 wherein R 50  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy and heterocyclyloxy;  
                     
 wherein R 51  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, haloalkyl, haloalkenyl, haloalkynyl; haloaryl, haloheteroaryl and haloheterocyclyl; and  
                     
 wherein R 53  selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
 
         or a pharmaceutically acceptable salt or tautomer thereof,  
         provided that when R 5  is selected from the group consisting of heterocyclylalkyl and heterocyclylalkenyl, the heterocyclyl radical of the corresponding heterocyclylalkyl or heterocyclylalkenyl is other than a δ-lactone; and  
         provided that when R 4  is aryl, heteroaryl or heterocyclyl, and one of R 2  and R 6  is trifluoromethyl, then the other of R 2  and R 6  is difluoromethyl.  
       
     
     
         27 . A compound represented by the generic formula:  
       
         
           
           
               
               
           
         
         wherein:  
         R 2  and R 6  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, fluorinated alkyl, fluorinated aralkyl, chlorofluorinated alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, alkoxyalkyl, and alkoxycarbonyl; provided that at least one of R 2  and R 6  is fluorinated alkyl, chlorofluorinated alkyl or alkoxyalkyl;  
         R 3  is selected from the group consisting of arylcarbonyl, heteroarylcarbonyl, hydroxymethyl, arylalkoxyalkyl, trialkylsilyloxyalkyl,  
         —CHO,  
         —CO 2 R 7 , 
 wherein R 7  is selected from the group consisting of hydrogen and alkyl; and  
                     
 wherein R 15a  is selected from the group consisting of hydroxy, halogen, alkylthio and alkoxy, and  
 R 16a  is selected from the group consisting of alkyl, haloalkyl, alkenyl, aryl and heteroaryl;  
 
         R 4  is selected from the group consisting of hydrogen, hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, heteroarylalkyl, alkoxy, thio, trialkylsilyl, alkylamino, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl;  
         R 5  is selected from the group consisting of hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aralkyl, alkoxy, aryloxy, cycloalkylthioalkyl, arylthioalkyl, heteroarylthioalkyl, alkoxyalkenyl, arylcarbonyloxyalkyl, pyrrolyl, substituted pyrrolidinyl, hydroxymethyl, arylalkoxyalkyl, and trialkylsilyloxyalkyl,  
         —CO 2 R 14 , 
 wherein R 14  is alkyl;  
                     
 wherein R 15b  is selected from the group consisting of hydroxy, halogen, alkoxy, and alkylthio, aroyloxy, and alkylsulfonyloxy, and  
 R 16b  is selected from the group consisting of alkyl, alkenyl, aryl, and heteroaryl;  
                     
 wherein R 17  and R 18  are independently alkyl;  
                     
 wherein R 19  is aryl, heteroaryl, —SR 20 , and —OR 21 ,  
 wherein R 20  is selected from the group consisting of aryl, heteroaryl and aminoalkyl, and  
 R 21  is selected from the group consisting of aryl and heteroaryl;  
                     
 wherein R 24  is aralkyl;  
                     
 wherein R 28  and R 29  are independently alkyl;  
                     
 wherein R 30  and R 31  are independently alkoxy;  
 
         —C≡C—Si(R 36 ) 3 , 
 wherein R 36  is alkyl;  
                     
 wherein R 37  is selected from the group consisting of hydrogen, alkoxy, and alkylthio, and  
 R 38  is selected from the group consisting of haloalkyl, cycloalkyl, heterocyclylalkoxy, and alkylthio;  
 provided that when R 37  is hydrogen, then R 38  is selected from the group consisting of haloalkyl, cycloalkyl, and heterocyclylalkoxy;  
                     
 wherein R 42  is selected from the group consisting of hydrogen and alkyl, and  
 R 43  is substituted heteroaryl;  
                     
 wherein R 44  is selected from the group consisting of aryl and heteroaryl;  
 
         —SR 45 , 
 wherein R 45  is selected from the group consisting of haloalkyl, heterocyclyl, alkylthioalkyl, aminocarbonylalkyl, —SR 46 , and —CH 2 R 47 ,  
 wherein R 46  is selected from the group consisting of aryl and heteroaryl, and  
 R 47  is selected from the group consisting of methylenedioxyphenyl, pyridyl, quinolinyl, tetrahydronaphthyl and benzodioxanyl;  
                     
 wherein R 48  is selected from the group consisting of hydrogen and alkyl, and  
 R 49  is selected from the group consisting of alkoxy and haloalkyl;  
                     
 wherein R 50  is selected from the group consisting of alkyl, alkoxy, and heteroaryl; and  
                     
 wherein R 51  is haloalkyl;  
 
         or a pharmaceutically acceptable salt or tautomer thereof,  
         provided that:  
         when R 2  is selected from the group consisting of difluoromethyl and trifluoromethyl, R 3  is selected from the group consisting of —CO 2 H, —CO 2 CH 3  and —CO 2 C 2 H 5 , R 5  is hydrogen, and R 6  is selected from the group consisting of hydrogen and trifluoromethyl, then R 4  is selected from the group consisting of cycloalkyl, cycloalkylalkyl, heteroarylalkyl, aralkenyl, alkoxy, thio, trialkylsilyl, alkylamino, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl; provided further that when R 2 , R 3  and R 5  are as defined above, and R 4  is alkoxy, then R 6  is hydrogen;  
         when R 2  is selected from the group consisting of fluorinated methyl and chlorofluorinated methyl, R 3  is selected from the group consisting of hydroxymethyl and CO 2 R 7 , R 5  is selected from the group consisting of hydroxymethyl and CO 2 R 14 , R 6  is selected from the group consisting of fluorinated methyl and chlorofluorinated methyl, and R 7  and R 14  are independently alkyl, then R 4  is selected from the group consisting of thio, trialkylsilyl, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl;  
         when R 2  is difluoromethyl, R 3  is —CO 2 C 2 H 5 , R 4  is hydrogen, R 5  is —CO 2 C 2 H 5 , then R 6  is selected from the group consisting of hydrogen, monofluoroalkyl, difluoroalkyl and alkoxyalkyl;  
         when R 2  is trifluoromethyl, R 3  is —CO 2 R 7 , R 5  is methyl, R 6  is selected from the group consisting of fluorinated methyl, fluorinated ethyl and chlorofluorinated methyl, and R 7  is selected from the group consisting of hydrogen and alkyl, then R 4  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heteroarylalkyl, thio, trialkylsilyl, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl;  
         when R 4  is selected from the group consisting of alkyl, cycloalkyl and cycloalkylalkyl, R 3  is —CO 2 R 7 , and R 7  is alkyl, then R 5  is other than arylcarbonyl, heteroarylcarbonyl or  
         
           
             
             
                 
                 
             
           
         
         wherein R 16b  is alkyl when R 15b  is selected from the group consisting of hydroxy, halogen, alkylthio and alkoxy, or wherein R 16b  is aryl or heteroaryl when R 15b  is hydroxy;  
         when R 4  is selected from the group consisting of alkyl, cycloalkyl and cycloalkylalkyl, R 5  is —CO 2 R 14 , and R 14  is alkyl, then R 3  is other than arylcarbonyl, heteroarylcarbonyl or  
         
           
             
             
                 
                 
             
           
         
         wherein R 16a  is alkyl when R 15a  is selected from the group consisting of hydroxy, halogen, alkylthio and alkoxy, or wherein R 16a  is aryl or heteroaryl when R 15a  is hydroxy; and  
         when R 2  and R 6  are independently selected from fluorinated methyl and chlorofluorinated methyl, R 3  is CO 2 R 7 , R 5  is hydroxy, alkoxy or aryloxy, then R 4  is selected from the group consisting of aryl, cycloalkyl, cycloalkylalkyl, heteroarylalkyl, thio, trialkylsilyl, alkylamino, and —OC(O)N(R 8 ) 2 , wherein R 8  is aryl; and  
         when R 4  is aryl and one of R 2  and R 6  is trifluoromethyl, then the other of R 2  and R 6  is difluoromethyl.
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