Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors

Abstract

The present invention relates to compounds of Formula I or II, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

1. A compound of Formula I or II: 
                 
 
       wherein A is independently selected from hydrogen; , —(C═O)—O—R 1 , —(C═O)—R 2 , —C(═O)—NH—R 2 , —C(═S)—NH—R 2 , or  and —S(O) 2 —R 2 ;    G is independently selected from —OH, —O—(C 1 -C 12  alkyl), —NHS(O) 2 —R 1 , —(C═O)—R 2 , —(C═O)—O—R 1 , or  and —(C═O)—NH—R 2 ;    L is absent or independently selected from —S—, —SCH 2 —, —SCH 2 CH 2 —, —S(O) 2 —, —S(O) 2 CH 2 CH 2 —, —S(O)—, —S(O)CH 2 CH 2 —, —O—, —OCH 2 —, —OCH 2 CH 2 —, —(C═O)—CH 2 —, —CH(CH 3 )CH 2 —, —CFHCH 2 —, or  and —CF 2 CH 2 —;    X and Y taken together with the carbon atoms to which they are attached form a cyclic moiety selected from aryl, substituted aryl, heteroaryl, or  and substituted heteroaryl;    W is absent, or independently selected from —O—, —S—, —NH—, —C(O)NR 1 — or  and —NR 1 —;    Z is independently selected from hydrogen; , —CN, —SCN, —NCO, —NCS, —NHNH 2 , —N 3 , halogen, —R 4 , —C 3 -C 12  cycloalkyl, substituted —C 3 -C 12  cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, and —NH—N═CH(R 1 );    each R 1  is independently selected from hydrogen, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, C 1 -C 6  alkenyl, substituted C 1 -C 6  alkenyl, C 1 -C 6  alkynyl, substituted C 1 -C 6  alkynyl, C 3 -C 12  cycloalkyl, substituted C 3 -C 12  cycloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heterocycloalkyl, or  and substituted heterocycloalkyl;    each R 2  is independently selected from hydrogen, C 1 -C 6  alkyl, C 1 -C 6  alkyl,  substituted C 1 -C 6  alkyl, C 1 -C 6  alkenyl, substituted C 1 -C 6  alkenyl, C 1 -C 6  alkynyl, substituted C 1 -C 6  alkynyl, C 3 -C 12  cycloalkyl, substituted C 3 -C 12  cycloalkyl, alkylamino, dialkylamino, arylamino, diarylamino, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heterocycloalkyl, or  and substituted heterocycloalkyl;    each R 4  is independently selected from: 
 (i) —C 1 -C 6  alkyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or  and N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or  and substituted heteroaryl;  
 (ii) —C 2 -C 6  alkenyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or  and N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or  and substituted heteroaryl; or  and 
 (iii) —C 2 -C 6  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or  and N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or  and substituted heteroaryl;  
   R 5  and R 6  are each independently selected from hydrogen or  and methyl;    each R 7  and R 8  is independently selected from: 
 (i) —C 1 -C 6  alkyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or substituted heteroaryl;    (ii) —C 2 -C 6  alkenyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; or    (iii) —C 2 -C 6  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or substituted heteroaryl;      j=0, 1, 2, 3, or 4;    m=0, 1, or  2; and     s=0, 1 or 2;    wherein each substituted alkyl, substituted alkynyl  alkenyl, substituted alkynyl, substituted aryl, substituted arylalkyl, substituted heteroaryl, substituted C 3 -C 12 -cycloalkyl, substituted heterocycloalkyl, and substituted heteroarylalkyl may independently replace one, two or three of the hydrogen atoms thereon with F, Cl, Br, I, OH, NO 2 , CN, C 1 -C 6 -alkyl-OH, C(O)—C 1 -C 6 -alkyl, OCH 2 —C 3 -C 12 -cycloalkyl, C(O)H, C(O)-aryl, C(O)-heteroaryl, CO 2 -alkyl, CO 2 -aryl, CO 2 -heteroaryl, CONH 2 , CONH—C 1 -C 6 -alkyl, CONH-aryl, CONH-heteroaryl, OC(O)—C 1 -C 6 -alkyl, OC(O)-aryl, OC(O)-heteroaryl, OCO 2 -alkyl, OCO 2 -aryl, OCO 2 -heteroaryl, OCONH 2 , OCONH—C 1 -C 6 -alkyl, OCONH-aryl, OCONH-heteroaryl, NHC(O)H, NHC(O)—C 1 -C 6 -alkyl, NHC(O)-aryl, NHC(O)-heteroaxyl  NHC( O )- heteroaryl , NHCO 2 -alkyl, NHCO 2 -aryl, NHCO 2 -heteroaryl, NHCONH 2 , NHCONH—C 1 -C 6 -alkyl, NHCONH-aryl, NHCONH-heteroaryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -heteroaryl, SO 2 NH 2 , SO 2 NH—C 1 -C 6 -alkyl, SO 2 NH-aryl, SO 2 NH-heteroaryl, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl, CF 3 , CH 2 CF 3 , CHCl 2 , CH 2 NH 2 , CH 2 SO 2 CH 3 , C 1 -C 6  alkyl,  halo alkyl, C 3 -C 12  cycloalkyl, substituted C 3 -C 12  cycloalkyl, aryl, substituted aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, benzyl, benzyloxy, aryloxy, heteroaryloxy, C 1 -C 6 -alkoxy, methoxymethoxy, methoxyethoxy, amino, benzylamino, arylamino, heteroarylamino, C 1 -C 3 -alkylamino, di-C 1 -C 3 -alkylamino, thio, aryl-thio, heteroarylthio, benzyl-thio, C 1 -C 6 -alkyl-thio, or methylthiomethyl.    
     
     
       2. The compound of  claim 1 , wherein the compound is of Formula III: 
                 
 
       wherein R 7  and R 8  are independently selected from R 4  as defined in  claim 1 . 
     
     
       3. The compound of  claim 1 , wherein the compound is of Formula IV: 
                 
 
       wherein R 7  and R 8  are independently selected from R 4  as defined in  claim 1 . 
     
     
       4. A compound according to any one of claims  1 - 3 , wherein W is absent and Z is thiophenyl. 
     
     
       5. A compound according to any one of claims  1 - 3 , wherein W is —CH═CH— and Z is thiophenyl. 
     
     
       6. A compound according to  claim 1  which is selected from:
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=2-(formamido)-thiazol-4-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=ethyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=phenyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=4-methoxyphenyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=4-ethoxyphenyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=5-bromothiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=2-pyrid-3-yl ethylenyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=3,4-Dimethoxy-phenyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=2-thiophen-2-yl ethylenyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, Z=indole-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=1H-indol-3-yl methyl   1 H- indol -   3   - ylmethyl , j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=furan-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=1H-benzoimidazol-2-yl   1 H- benzoimidazol -   2   - yl , j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z =1H-imidazol-2-ylmethyl   1 H- imidazol -   2   - ylmethyl , j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OEt, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=chloro, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, Z=thiophen-3-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=2-pyrid-3-yl acetylenyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=2,3-dihydrobenzofuran-5-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W=—NH—, Z=propargyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W=—N(ethyl)-, Z=benzyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W=—NH—, Z=pyrid-3-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=tetrazolyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=morpholino, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W=—O—, Z=thiophen-3-yl-methyl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OEt, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=tBOC, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are 
                 
 
 
       W is absent, Z=thiophen-2-yl, j=3, m=s=1, R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , wherein R 1 =cyclopentyl, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , wherein R 1 =cyclobutyl, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , wherein R 1 =cyclohexyl, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , wherein R 1 =
                 
 
 
       G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , wherein R 1 =
                 
 
 
       G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , wherein R 1 =
                 
 
 
       G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;
 Compound of Formula I, wherein A=—(C═O)—R 1 , wherein R 1 =cyclopentyl, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—NH—R 1 , wherein R 1 =cyclopentyl, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C=S)—NH—R 1 , wherein R 1 =cyclopentyl, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—S(O) 2 —R 1 , wherein R 1 =cyclopentyl, G=OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , R 1 =cyclopentyl, G=—O-phenethyl, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , R 1 =cyclopentyl, G=—NH-phenethyl, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , R 1 =cyclopentyl, G=—NHS(O) 2 -phenethyl L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , R 1 =cyclopentyl, G=—(C═O)—OH, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , R 1 =cyclopentyl, G=—(C═O)—O-phenethyl, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , R 1 =cyclopentyl, G=—(C═O)—NH-phenethyl, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=—(C═O)—O—R 1 , R 1 =cyclopentyl, G=—(C═O)—NH—S(O) 2 -benzyl, L=absent, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=—(C═O)CH 2 —, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=—CH(CH 3 )CH 2 —, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=—O—, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, R 5 =methyl, and R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=—S—, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, R 5 =methyl, and R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=—S(O)—, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, R 5 =methyl, and R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=—S(O) 2 , X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, R 5 =methyl, and R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=—SCH 2 CH 2 —, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, R 5 =methyl, and R 6 =hydrogen;  
 Compound of Formula I, wherein A=tBOC, G=OH, L=CF 2 CH 2 , X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen; and  
 Compound of Formula I, wherein A=tBOC, G=OH, L=—CHFCH 2 —, X and Y taken together with the carbon atoms to which they are attached are phenyl, W is absent, Z=thiophen-2-yl, j=3, m=s=1, and R 5 =R 6 =hydrogen.  
 
     
     
       7. A compound of Formula V: 
                 
 
       wherein A is selected from: 
                 
                 
 
       and B is selected from: 
                 
                 
                 
                 
                 
                 
                 
                 
 
     
     
       8. A compound of  claim 7  selected from the following compounds:
                                                             Compound   B   Compound   B           101301                         101358                           101306                         101302                           101322                         101311                           101325                         101303                           101326                         101327                           101330                         101331                           101332                         101335                           101336                         101348                           101340                         101334                           101348                         101359                           101328                         101360                           101361                         101362                           101329                         101324                           101304                         101355                           101356                         101307                           101357                         101347                           101352                         101364                           101308                         101309                           101367                         101368                           101323                         101317                           101318                         101319                           101351                         101353                           101349                         101333                           101320                         101321                           101347                         101350                           101313                         101366                           101354                         101343                           101314                         101339                           101341                         101345                           101344                         101342                           101315                         101346                           101337                         101338                                                                                    
 ! 
                                                             Compound   A   Compound   A           105301                         123301                           112301                         124301                           109301                         122301                           111301                         114301                           107301                         104301                           110301                         128301                           124301                         113301                           143301                         115301                           108301                         118301                           120301                         129301                           121301                         117301                           145301                         106301                           144301                         126301                           127301                         130301                           116301                         102301                           140301                         141301                           139301                         138301                           142301                         137301                           135301                         134301                           133301                         131301                           132301                         136301                                                                         
 ! 
                 
                 
 
 
     
     
       9. A pharmaceutical composition comprising an inhibitory amount of a compound according to  claim 1  or  7  alone or in combination with a pharmaceutically acceptable carrier or excipient. 
     
     
       10. A method of treating a hepatitis C viral infection in a subject, comprising administering to the subject an inhibitory amount of a pharmaceutical composition according to  claim 9 . 
     
     
       11. The compound of  claim 1 , wherein
   L is absent;        X and Y taken together with the carbon atoms to which they are attached form a cyclic moiety selected from aryl and substituted aryl;        j= 3 ;        m= 1 ;        s= 1 ; and        R   5    and R   6    are hydrogen.     
     
     
       12. The compound of  claim 11  wherein W is absent. 
     
     
       13. A pharmaceutical composition comprising an anti- hepatitis C virally effective amount of a compound according to    claim 11   , or a pharmaceutically acceptable salt, ester, or prodrug thereof, in combination with a pharmaceutically acceptable carrier or excipient.   
     
     
       14. A method of treating a hepatitis C viral infection in a subject, comprising administering to the subject an anti- hepatitis C virally effective amount of a pharmaceutical composition according to    claim 13   .