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Anti Viral Compounds

Abstract: Compounds effective in inhibiting replication of Hepatitis C virus ("HCV") are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

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Patent Information

Application #
Filing Date
08 July 2011
Publication Number
04/2012
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
Parent Application

Applicants

ABBOTT LABORATORIES
100 ABBOTT PARK ROAD, ABBOTT PARK, IL 60064-6008 UNITED STATES OF AMERICA

Inventors

1. DEGOEY, DAVID, A.
8649 226TH AVENUE, SALEM, WI 53168 UNITED STATES OF AMERICA
2. DONNER, PAMELA, L.
1901 MCRAE LANE, MUNDELEIN, IL 60060 UNITED STATES OF AMERICA
3. KATI, WARREN, M.
152 KNOBB HILL LANE, GURNEE, IL 60031 UNITED STATES OF AMERICA
4. HUTCHINS, CHARLES, W.
31005 PRAIRIE RIDGE ROAD, GREEN OAKS, IL 60048 UNITED STATES OF AMERICA
5. KRUEGER, ALLAN, C.
7260 PRESIDENTIAL DRIVE, GURNEE, IL 60031 UNITED STATES OF AMERICA
6. RANDOLPH, JOHN, T.
304 BROADWAY AVENUE, LIBERTYVILLE, IL 60064 UNITED STATES OF AMERICA
7. MOTTER, CHRISTOPHER, E.
10135 SOUTH WARWICK DRIVE, OAK CREEK, WI 53154 UNITED STATES OF AMERICA
8. KRISHNAN, PREETHI
17718 W. RUNNING CREEK COURT, GURNEE, IL 60031 UNITED STATES OF AMERICA
9. MISTRY, NEETA, C.
1440 HUNTINGTON DRIVE, MUNDELEIN, IL 600960 UNITED STATES OF AMERICA
10. PILOT-MATIAS, TAMI, J.
2100 CRANBROOK ROAD, GREEN OAKS, IL 60048 UNITED STATES OF AMERICA
11. PATEL, SACHIN, V.
1325 S. WHITE OAK DRIVE, #1725, WAUKEGAN, IL 60085 UNITED STATES OF AMERICA
12. LI, XIAOYAN
1220 S. WHITE OAK DRIVE, #1018, WAUKEGAN, IL 60085 UNITED STATES OF AMERICA
13. SOLTWEDEL, TODD, N.
4808 W. STRONG STREET, 1ST FLOOR, CHICAGO, IL 60630 UNITED STATES OF AMERICA
14. NELSON, LISSA, T.
640 BROADVIEW AVENUE, HIGHLAND PARK, IL 60035 UNITED STATES OF AMERICA

Specification

ANT1-VIRAL COMPOUNDS This application claims the benefit from and incorporates herein by references the entire content of U.S. Provisional Application No. 61/140,318, filed December 23, 2008. FIELD The present invention relates to compounds effective in inhibiting replication of Hepatitis C virus ("HCV"). The present invention also relates to compositions comprising these compounds and methods of using these compounds to treat HCV infection. BACKGROUND HCV is an RNA virus belonging to the Hepacivirus genus in the Flaviviridae family. HCV has enveloped virions that contain a positive stranded RNA genome encoding all known virus-specific proteins in one single, uninterrupted, open reading frame. The open reading frame comprises approximately 9500 nucleotides encoding a single large polyprotein of about 3000 amino acids. The polyprotein comprises a core protein, envelope proteins El and E2, a membrane bound protein p7, and the non-structural proteins NS2, NS3, NS4A, NS4B, NS5A and NS5B. HCV infection is associated with progressive liver pathology, including cirrhosis and hepatocellular carcinoma. Chronic hepatitis C may be treated with peginterferon-alpha in combination with ribavirin. Substantial limitations to efficacy and tolerability remain as many users suffer from side effects and viral elimination from the body is often inadequate. Therefore, there is a need for new drugs to treat HCV infection. SUMMARY The present invention features compounds of Formulae I, II and III, and pharmaceutically acceptable salts thereof. These compounds and salts are capable of inhibiting the replication of HCV. The present invention also features compositions comprising the compounds or salts of the present invention. The compositions can also include other therapeutic agents, such as HCV helicase inhibitors, HCV polymerase inhibitors, HCV protease inhibitors, NS5A inhibitors, CD81 inhibitors, cyclophilin inhibitors, or internal ribosome entry site (IRES) inhibitors. The present invention further features methods of using the compounds or salts of the present invention to inhibit HCV replication. The methods comprise contacting cells infected with HCV virus with a compound or salt of the present invention, thereby inhibiting the replication of HCV virus in the cells. In addition, the present invention features methods of using the compounds or salts of the present invention, or compositions comprising the same, to treat HCV infection. The methods comprise administering a compound or salt of the present invention, or a pharmaceutical composition comprising the same, to a patient in need thereof, thereby reducing the blood or tissue level of HCV virus in the patient. The present invention also features use of the compounds or salts of the present invention for the manufacture of medicaments for the treatment of HCV infection. Furthermore, the present invention features processes of making the compounds or salts of the invention. Other features, objects, and advantages of the present invention are apparent in the detailed description that follows. It should be understood, however, that the detailed description, while indicating preferred embodiments of the invention, are given by way of illustration only, not limitation. Various changes and modifications within the scope of the invention will become apparent to those skilled in the art from the detailed description. DETAILED DESCRD?TION The present invention features compounds having Formula I, and pharmaceutically acceptable salts thereof, wherein: A1 is C5-C10carbocyclyl or 5- to 10-membered heterocyclyl, and is substituted with -X1-R7, wherein said C5-C10carbocyclyl and 5- to 10-membered heterocyclyl are optionally substituted with one or more RA; A2 is C5-C10carbocyclyl or 5- to 10-membered heterocyclyl, and is substituted with -X2-Rg, wherein said C5-Ciocarbocyclyl and 5- to 10-membered heterocyclyl are optionally substituted with one or more RA; XI and X2 are each independently selected from a bond, -Ls-, -O-, -S-, or -N(RB)-; R7 and Rg are each independently selected from hydrogen, -LA, C5-C10carbocyclyl, or 5- to 10- membered heterocyclyl, wherein at each occurrence said C5-C10carbocyclyl and 5- to 10- membeTed heterocyclyl are each independently optionally substituted with one or more RA; Z1 and Z2 are each independently selected from a bond, -C(RcRc)-, -O-, -S-, or -N(RB)-; Wi, W2, W3, and W4 are each independently selected from N or C(RD), wherein RD is independently selected at each occurrence from hydrogen or RA; R1 and R2 are each independently selected from hydrogen or RA; R3 and R4 are each independently selected from hydrogen or RA; or R3 and R4, taken together with the carbon atoms to which they are attached, form a C5-C10carbocyclic or 5- to 10-membered heterocyclic ring, wherein said C5-C10carbocyclic and 5- to 10-membered heterocyclic ring are optionally substituted with one or more RA; R5 and R6 are each independently selected from hydrogen or RA; or R5 and R6, taken together with the carbon atoms to which they are attached, form a C5-C10carbocyclic or 5- to 10-membered heterocyclic ring, wherein said C5-C10carbocyclic and 5- to 10-membered heterocyclic ring are optionally substituted with one or more RA; T is selected from a bond, -Ls~, -Ls-M-Ls'-, -Ls-M-LS'-M'-Ls-, wherein M and M' are each independently selected from a bond, -0-, -S-, -N(RB)-, -C(O)-, -S(O)2-, -S(O)-, -OS(O)-, -OS(O)2-, -S(O)20-, -S(O)O- -C(O)O-, -OC(O)-, -OC(O)O- -C(O)N(RB)- - N(RB)C(Q)-, -N(RB)C(O)O- -OC(O)N(RB)-, -N(RB)S(O)-, -N(RB)S(O)2- -S(O)N(RR)- - S(O)2N(RB)-, -C(O)N(RD)C(O)-, -N(RB)C(O)N(RB.)-, -N(RB)SO2N(RB.)- - N(RB)S(O)N(RB)-, C5-C10carbocycle, or 5- to 10-membered heterocycle, and wherein T is optionally substituted with one or more RA; RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl, cyano, -LA, or -LS-RE; RB and RB- are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, C3-C6Carbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6-membered heterocyclyl, or (3- or 6-membered heterocycly^CrCgalkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; Rc and Rc' are each independently selected at each occurrence from hydrogen; halogen; hydroxy; mercapto; amino; carboxy; nitro; phosphate; oxo; thioxo; formyl; cyano; or C1-C6alkyl, C2- Cealkenyl, C2-C6alkynyl, or C3-C6carbocyclyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; LA is independently selected at each occurrence from d-Cealkyl, C2-C6alkenyl, or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, -N(RsRs.), -OC(O)Rs, -G(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; Lg, Ls- and Lg- are each independently selected at each occurrence from a bond; or C1-C6alkylene, C2-C6alkenylene, or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, - N(RsRs-), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; RE is independently selected at each occurrence from -O-Rs, -S-Rs, -C(O)Rs, -OC(O)Rs, - C(O)ORs, -N(RSRS.), -S(O)RS) -SO2Rs, -C(O)N(RsRs), -N(Rs)C(O)RSN - N(Rs)C(O)N(Rs-RS"), -N(Rs)S02RS', -S02N(RsRs.), -N(Rs)S02N(R.s.Rs..), - N(Rs)S(O)N(Rs-Rs"), -OS(O)-Rs, -OS(O)2-Rs, -S(O)2ORs, -S(O)ORs, -OC(O)ORs, - N(Rs)C(O)ORs., -OC(O)N(RsRs.), -N(Rs)S(O)-Rs-, -S(O)N(RsRs), -C(O)N(Rs)C(O)-Rs., C3-C6carbocyclyl, or 3- to 6-membered heterocyclyl, and said C3-C6caxbocyclyl and 3- to 6- membered heterocyclyl are each independently optionally substituted at each occurrence with one or more substituents selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Rs (except hydrogen), halogen, -0-RB, -S-RB, -N(RBRB), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano; and Rs, Rs' and Rs- are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6- membered heterocyclyl, or (3- to 6-membered heterocyclyl)C1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -0-RB, -S-RB, -N(RBRB), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano. Ai and A2 are preferably independently selected from C5-C6carbocycles or 5- to 6-membered heterocycles (e.g., phenyl, thiazolyl, thienyl, pyrrolidinyl or piperidinyl), and are each independently optionally substituted with one or more RA- A1 and A2 arc substituted with -X1-R7 and -X2-R8, respectively. The ring system in A1 can be identical to, or different from, that in A2. For instance, A1 and A2 can both be phenyl, or one is phenyl and the other is thiazolyl. Z1 and T can be attached to A1 via any two substitutable ring atoms on A1, and Z2 and T can be attached to A2 via any two substitutable ring atoms on A2. Two adjacent RA on A1 (or A2), taken together with the ring atoms to which they are attached, may form a C5-C6carbocycle or a 5- to 6-membered heterocycle. Preferably, Rs and R4, taken together with the carbon atoms to which they are attached, form a C5-C6carbocycle or a 5- to 6-membered heterocycle, which is optionally substituted with one or more RA. Non-limiting examples of suitable 5- to 6-membered carbocycles or heterocycles include hydrogen or RA. Preferably, Rg, R10, R11, R12, R13, and R14 are each independently selected from hydrogen; halogen; or C1-C6aIkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, or C3- C6carbocyclyC1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano. Highly preferably, R9 and R12 are each independently selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl (e.g., C3-C6Cycloalkyl), or C3-C6CarbocyclyC1-C6alkyl (e.g., C3-C6cycloalkylC1-C6alkyl), each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; and R10, R11, R13 and R14 are hydrogen. R7 and Rg are preferably independently selected from C5-C6carbocycles or 5- to 6-membered heterocycles, and are each independently optionally substituted with one or more RA. The ring system in R7 can be identical to, or different from, that in Rg. More preferably, both R7 and Rg are phenyl, and are each independently optionally substituted with one or more RA (e.g., -N(RsRs), such as - NH2). X1 and X2 arc preferably independently selected from -CH2-, -O-, or -S-. Z1 and Z2 are preferably independently -N(RB)-, such as -NH- or -N(C1-C6alkyl)-. T can be selected, without limitation, from the following moieties: where k is 1 or 2, R and R* are independently hydrogen or C1-C6alkyl, and R' and R" are independently C1-C6alkyl or C6-C10aryl. Preferably, T is selected from Table 4 described below. More preferably, T is -LS-N(RT)-LS.- (e.g., -CH2-N(RT)-CH2-), or -LS-C(RTRT')-LS- (e.g., -CH2-C(RTRT')-CH2-). RT is C1-C6alkyl, C2-C6alkenyl, or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, -N(RsRs), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; or RT is C3-C6carbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6-membered heterocyclyl, or (3- or 6-membered heterocyc1y1)CrC6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, Rs (except hydrogen), halogen, -O-RB, -S-RB, -N(RBRB), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano. Rr is RA, and preferably Rr is hydrogen. Ls, Ls, RA, RB, RB', Rs, and Rs' are as defined above. In one embodiment, A1 is a 5- to 6-mcmbered carbocycle or heterocycle (e.g., phenyl, thiazolyl, thienyl, pyrrolidinyl or piperidinyl), which is substituted with -Xx-R7 and is optionally substituted with one or more RA; and A2 is a 5- to 6-membered carbocycle or heterocycle (e.g., phenyl, thiazolyl, thienyl, pyrrolidinyl or piperidinyl), which is substituted with -X2-R8 and is optionally substituted with one or more RA. R3 and R4, taken together with the carbon atoms to which they are attached, form a 5- to 6-membered carbocycle or heterocycle which is optionally substituted with one or more RA' R5 and R6, taken together with the carbon atoms to which they arc attached, also form a 5- to 6-membered carbocycle or heterocycle which is optionally substituted with one or more RA. Preferably, both A1 and A2 are phenyl, and are substituted with -X1-R7 and -X2-R8, respectively, where X1 and X2 preferably are independently selected from -CH2-, -O-, or -S-, and R7 and Rs preferably are phenyl and are each independently optionally substituted with one or more RA. In another embodiment, at least one of R7 and Rg is a 5- to 6-membered carbocycle or heterocycle (e.g., phenyl), which is optionally substituted with one or more RA. In still another embodiment, R7 and R« are each independently selected from 5- to 6-membered carbocycles or heterocycles, and are each independently optionally substituted with one or more RA. In a further embodiment, Wi, W2, W3 and W4 are N, and Zy and Z2 are independently - N(RB)-. Preferably, Zx and Z2 are independently selected from -NH-, -N(C1-C6alkly)-, -N(C2- C6alkenyl)-, -N(C2-C6alkynyl)-, -N(C1-C6haloalkyl)-, -N(C2-C6haloalkenyl)-, or -N(C2- Cehaloalkynyl)-. More preferably, Z1 and Z2 are independently selected from -NH- or -N(C1- C6alkly)-. In still another embodiment, R3 and R4, taken together with the carbon atoms to which they N(C1-C6alMy)-); and at least one of X1 and X2 is -CH2-, -O-, or -S-. Preferably, at least one of R7 and R8 is phenyl, and is optionally substituted with one or more RA- More preferably, R1 and R2 are hydrogen; and R9, R10, Rn, R12, R13, and R14 are each independently selected from hydrogen; halogen; or C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, or C3-C6carbocyclylC1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano. Highly preferably, R9 and R12 are each independently selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl (e.g., C3-C6cycloalkyl), or C3-C6carbocyclyC1-C6alkyl (e.g., C3- C6cycloalkylC1-C6alkyl), each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; and R10, R11, R13 and R14 are hydrogen. In yet another embodiment, R3 and R4, taken together with the carbon atoms to which they are hydrogen or RA; W1, W2, W3 and W4 are N; Z1 and Z2 are independently -N(RB)- (e.g., -NH- or - N(C1-C6alkly)-); and X1 and X2 are each independently selected from -CH2-, -O-, or -S-. Preferably, R7 and R8 are phenyl, and are each optionally substituted with one or more RA. More preferably, R1 and R2 are hydrogen; and R9, R10, R11, R12, R13, and R14 are each independently selected from hydrogen; halogen; C1-Cealkyl, C2-C6alkenyl, C2-C,5alkynyl, C3-C6carbocyclyl, or C3- C6carbocyclyC1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano. Highly preferably, R9 and R12 are each independently C1- C6alkyl, C2-C6;alkenyl, C2-C6alkynyl, C3-C6carbocyclyl (e.g., C3-C6cycloalkyl), or C3-C6carbocyclyC1- C6alkyl (e.g., C3-C6CycloalkylC1-C6alkyl), each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; and R10, R11, R13 and R14 are hydrogen. fn another embodiment, R3 and R4 are each independently selected from hydrogen or RA, and/or R5 and R6 are each independently selected from hydrogen or RA; and at least one of R7 and R8 is a 5- to 6-membered carbocycle or heterocycle (e.g., phenyl), which is optionally substituted with one or more RA- Preferably, R7 and Rg are each independently selected from 5- to 6-membered carbocycles or heterocycles, and are each independently optionally substituted with one or more RA In still another embodiment, R3 and R4 are each independently selected from hydrogen or RA, and/or R5 and R$ are each independently selected from hydrogen or RA; A1 is a 5- to 6-membered carbocycle or heterocycle (e.g., phenyl, thiazolyl, thienyl, pyrrolidinyl or piperidinyl), which is substituted with -X1-R7 and is optionally substituted with one or more RA; and A2 is a 5- to 6- membered carbocycle or heterocycle (e.g., phenyl, thiazolyl, thienyl, pyrrolidinyl or piperidinyl), which is substituted with -X2-R8 and is optionally substituted with one or more RA. Both A1 and A2 preferably are phenyl, and are substituted with -X1R7 and -X2-R8, respectively. X1 and X2 preferably are independently selected from -CH2-, -O- or -S-. R7 and Rg preferably are each independently selected from 5- to 6-membered carbocycles or heterocycles, and are each independently optionally substituted with one or more RA. More preferably, R7 and Rs are phenyl, and are each independently optionally substituted with one or more RA. W1, W2, W3 and W4 preferably are N. Z1 and Z2 preferably are independently -N(RB)-, such as -NH-, -N(C1-C6alkly)-, -N(C2-C6alkenyl)-, -N(C2- C6alkynyl)-, -N(CrC6haloalkyl)-, -N(C2-C6haloalkenyl)-, or -N(C2-Cshaloarkynyl)-. More preferably, Zi and Z2 are independently selected from -NH- or -N(C1-C6alkly)-. The present invention also features compounds having Formula n, and pharmaceutical^ acceptable salts thereof, wherein: X1 and X2 are each independently selected from a bond, -Ls-, -O-, -S-, or -N(RB)-; R7 and R8 are each independently selected from hydrogen, -LA, C5-C10carbocyclyl, or 5- to 10- membered heterocyclyl, wherein at each occurrence said C5-C10carbocyclyl and 5- to 10- membered heterocyclyl are each independently optionally substituted with one or more RA; Z1 and Z2 are each independently selected from a bond, -C(RcRc') -O-, -S-, or -N(RB)-; W1, W2, W3, W4 , W5, W6, W7, and W8 are each independently selected from N or C(RD), wherein RD is independently selected at each occurrence from hydrogen or RA; R1, R2, R9, R11, R12, R14, R15, and R16 are each independently selected at each occurrence from hydrogen or RA; m and n are each independently selected from 0, 1, 2, or 3; T is selected from a bond, -Ls-, -Ls-M-Ls—, -Ls-M-Ls-M'-Ls-, wherein M and M' are each independently selected from a bond, -O-, -S-, -N(RB)-, -C(O)-, -S(O)2- -S(O)-, -OS(G)-, -OS(O)2- -S(O)20-, -S(O)O- -C(O)O-, -OC(O)-, -OC(O)O- -C(O)N(RB)- - N(RB)C(O)-, -N(RB)C(O)O- -OC(O)N(RB)-, -N(RB)S(O)-, -N(RB)S(O)2-, -S(O)N(RB)-, - S(O)2N(RB)-, -C(O)N(RB)C(O)-, -N(RB)C(O)N(RB.)-, -N(RB)S02N(RB.)-, - N(RB)S(O)N(RB)-, C5-C10carbocycle, or 5- to 10-membered heterocycle, and wherein T is optionally substituted with one or more RA; RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl, cyano, -LA, or -LS-RE; RB and RB- are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2- Cealkenyl, C2-C6alkynyl, C3-C6carbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6-membered heterocyclyl, or (3- or 6-membered heterocyclyl)C1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; Rc and Rc are each independently selected at each occurrence from hydrogen; halogen; hydroxy; mercapto; amino; carboxy; nitro; phosphate; oxo; thioxo; formyl; cyano; or C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, or C3-C6carbocyclyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; LA is independently selected at each occurrence from C1-C6alkyl, C2-C6alkenyl, or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-RS) -S-Rs, -N(RsRg.), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; Ls, Ls' and Ls- are each independently selected at each occurrence from a bond; or C1-C6alkylene, C2-C6alkenylene, or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, - N(RsRs), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; RE is independently selected at each occurrence from -O-Rs, -S-Rs, -C(O)Rs, -OC(O)Rs, - C(O)ORs, -N(RsRsO, -S(O)Rs, -S02Rs, -C(O)N(RsRs), -N(Rs)C(O)Rs., - N(Rs)C(O)N(Rs.RS"), -N(Rs)S02RS', -SO2N(RsRs0, -N(Rs)SO2N(Rs-Rs"), N(Rs)S(O)N(RsRs-), -OS(O)-Rs, -OS(O)2-Rs, -S(O)2ORS, -S(O)ORs, -OC(O)ORs, - N(Rs)C(O)ORs., -OC(O)N(RsRs0, -N(Rs)S(O)-Rs-, -S(O)N(RsRs.), -C(O)N(Rs)C(O)-Rs., C3-C6carbocyclyl, or 3- to 6-membered heterocyclyl, and said C3-C6carbocyclyl and 3- to 6- membered heterocyclyl are each independently optionally substituted at each occurrence with one or more substituents selected from C1-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, Rs (except hydrogen), halogen, -O-RB, -S-RB, -N(RBRB.), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano; and Rs, Rs- and Rs- are each independently selected at each occurrence from hydrogen; or C1-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, C3-Cscarbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6- membered heterocyclyl, or (3- to 6-membered heterocyclyl)C1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-RB, -S-RB, -N(RBRB0, -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano. Z1 and Z2 are preferably independently -N(RB)-, such as -NH- or -N(C1-C6alkyl)-. X1 and X2 are preferably independently selected from -CH2-, -O-, or -S. R7 and Rs are preferably independently selected from C5-C6carbocycles or 5- to 6-membcrcd heterocycles, and are each independently optionally substituted with one or more RA. The ring system in R7 can be identical to, or different from, that in R8. More preferably, both R7 and Rs are phenyl, and are each independently optionally substituted with one or more RA (e.g., -N(RsRs) such as - NH2). where k is 1 or 2, R and R* are independently hydrogen or C1-C6alkyl, and R' and R" are independently C1-C6alkyl or C6-C10aryl. Preferably, T is selected from Table 4 described below. More preferably, T is -LS-N(RT)-LS- (e.g., -CH2-N(RT)-CH2-), or-Ls-C(RTRT')-Ls- (e.g., -CH2-C(RTRT')-CH2-). RT is CrC6alkyl, C2-Csalkenyl, or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, -N(RsRs-)> -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; or RT is C3-C6carbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6-membered heterocyclyl, or (3- or 6-membered heterocyclyljCrQalkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Rs (excepthydrogen), halogen, -O-RB, -S-RB, -N(RBRB), -OC(O)RB,-C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano. RT- is RA) and preferably RT- is hydrogen. Ls, Ls-, RA, RB, RB', RS. and Rs' are as defined above. In one embodiment, at least one of X1 and X2 is selected from -CH2-, -O-, or -S-; at least one of R7 and Rg is selected from 5- to 6-membered carbocycles or heterocycles, and is optionally substituted with one or more RA; and Z1 and Z2 are each independently -N(RB)- (e.g., -NH- or - N(C,-C6alkyl)-). In another embodiment, X1 and X2 are each independently selected from -CH2-, -O-, or -S-; R7 and Rs are each independently selected from C5-Cscarbocycles or 5- to 6-membered heterocycles, and are each independently optionally substituted with one or more RA; and Z1 and Z2 are each independently -N(RB)- (e.g., -NH- or -N(CrC6alkyl)-). In still another embodiment, Wi, W2, W3, W4 , W5, and W7 are N, and W6 and W8 are each independently C(RD); RI and R2 are hydrogen; R7 and Rg are phenyl, and are each independently optionally substituted with one or more RA; and R9, R11, R12, R14, and RD are each independently selected at each occurrence from hydrogen; halogen; C1-C6alkyl, C2-Cealkenyl, C2-C6alkynyl, C3- Cecarbocyclyl, or C3-C6carbocyclylC1-C6aIkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano. Preferably, R9 and R12 are each independently CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl (e.g., C3-C6cycloalkyl), or C3-C6carbocyclyC1-C6alkyl (e.g., C3-C6cycloalkylCrC6alkyl), each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; and Rn, R14 and RD are hydrogen. The present invention further features compounds having Formula III, and pharmaceutically acceptable salts thereof, wherein: X1 and X2 are each independently selected from a bond, -Ls-, -O-, -S-, or -N(RB)-; R7 and R8 are each independently selected from hydrogen, -LA, C5-C10carbocyclyl, or 5- to 10- membered heterocyclyl, wherein at each occurrence said C5-C10carbocyclyl and 5- to 10- membered heterocyclyl are each independently optionally substituted with one or more RA; ZI and Z2 are each independently selected from a bond, -C(RcRc)--, -O-, -S-, or -N(RB)-; Wi, W2, W3, W4, W5, W6, W7, and W8 are each independently selected from N or C(RD), wherein RD is independently selected at each occurrence from hydrogen or RA; R1, R2, R9, R11, R12, R14, R15, and Rl6 are each independently selected at each occurrence from hydrogen or RA; m and n are each independently selected from 0, 1,2, or 3; T is selected from a bond, -Ls-, -Ls-M-Ls—, -Ls-M-Ls—M'-Ls>-, wherein M and M' are each independently selected from a bond, -O-, -S-, -N(RB)-, -C(O)-, -S(O)2- -S(O)-, -OS(O)- -OS(O)2- -S(O)20- -S(O)O-, -C(O)O- -OC(O)-, -OC(O)O- -C(O)N(RB)- - N(RB)C(O)-, -N(RB)C(O)O- -OC(O)N(RB)-, -N(RB)S(O)-, -N(RB)S(O)2- -S(O)N(RB)-, - S(O)2N(RBK -C(O)N(RB)C(O)-, -N(RB)C(O)N(RB.)-, -N(RB)S02N(RB.)-, - N(RB)S(O)N(RB)-, C5-C10carbocycle, or 5- to 10-membered heterocycle, and wherein T is optionally substituted with one or more RA; RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl, cyano, -LA, or -LS-RE; RB and RB' are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, C3-CscarbocyclylC1-C6alkyl, 3- to 6-membered heterocyclyl, or (3- or 6-membered heterocyclyl)C1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; Re and Re are each independently selected at each occurrence from hydrogen; halogen; hydroxy; mercapto; amino; carboxy; nitro; phosphate; oxo; thioxo; formyl; cyano; or C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, or C3-C6arbocyclyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; LA is independently selected at each occurrence from CrC6alkyl, C2-C6alkenyl, or C2-C6alkyny1, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, -N(RsRs<), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; Ls, Ls- and Ls- are each independently selected at each occurrence from a bond; or C1-Csalkylene, C2-C6alkenylene, or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, - N(RsRs-), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; RE is independently selected at each occurrence from -O-Rs, -S-Rs, -C(O)Rs, -OC(O)Rs, - C(O)ORs, -N(RsRsO. -S(O)Rs, -S02Rs, -C(O)N(RsRs0, -N(Rs)C(O)Rs., - N(Rs)C(O)N(Rs.RS")3 -N(Rs)S02Rs., -S02N(RsRs.), -N(Rs)S02N(Rs-Rs"), - N(Rs)S(O)N(Rs.Rs0, -OS(O)-Rg, -OS(O)2-Rs, -S(O)2ORs, -S(O)ORs, -OC(O)ORs, - N(Rs)C(O)ORs', -OC(O)N(RsRs'), -N(Rs)S(O)-Rs, -S(O)N(RsRs), -C(O)N(Rs)C(O)-Rs', Ca-Cgcarbocyclyl, or 3- to 6-membered heterocyclyl, and said C3-C6carbocyclyl and 3- to 6- membered heterocyclyl are each independently optionally substituted at each occurrence with one or more substituents selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Rs (except hydrogen), halogen, -O-RB, -S-RB, -N(RBRB), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano; and Rs, Rs' and Rs- arc each independently selected at each occurrence from hydrogen; or CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6- membered heterocyclyl, or (3- to 6-membered heterocyclyl)C1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-RB, -S-RB, -N(RBRB.), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano. Z1 and Z2 are preferably each independently -N(RB)-, such as -NH- or -N(C1-C6alkyl)-. X1 and X2 are preferably independently selected from -CH2-, -O-, or -S. R7 and Rg are preferably independently selected from C5-C6carbocycles or 5- to 6-membered heterocycles, and are each independently optionally substituted with one or more RA. The ring system in R7 can be identical to, or different from, that in Rg. More preferably, both R7 and Rg are phenyl, and are each independently optionally substituted with one or more RA (e.g., -N(RsRs) such as - NH2). T can be selected, without limitation, from the following moieties: Preferably, T is selected from Table 4 described below. More preferably, T is -LS-N(RT)-LS- (e.g., -CH2-N(RT)-CH2-), or-Ls-C(RTRT')-Ls- (e.g., -CH2-C(RTRT')"CH2~). RT is CrC6alkyl, C2-C6alkenyl, or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, -N(RsR3. Dried over MgSCU, filtered and evaporated to yield the title compound as a brown solid (110 mg) and the product was used without further purification. The product of Example 4E (110 mg, 0.105 mmol) was dissolved in dichloromethane (0.3 mL) and TFA (2.7 mL) and the solution was stirred at room temperature for 30 minutes. The solvent was evaporated and the residue was extracted with 30% MeOH in dichloromethane and washed with IN Na2C03. Dried over MgSO4, filtered and evaporated. Purification by chromatography on silica gel cluting with 0-10% MeOH in dichloromethane gave the title compound as a light yellow solid (22 mg, 25% yield). 1H NMR (300MHz, DMSO-d6) : § 10.10 (s, 2H), 8.88 (d, J=8.1 Hz, 2H), 8.56 (s, 2H), 7.78 (m, 2H), 7.73 (s, 4H), 7.61 (m, 4H), 7.14 (d, J=8.5 Hz, 4H), 6.91 (d, J=7.7Hz, 2H), 6.61 (d, J=8.2 Hz, 4H), 5.53 (s, 4H), 3.20 (m, 2H), 1.34 (d, J=7.0 Hz, 12H). MS (ESI) m/z 849 (M+H)+. To a solution of the product from Example IE (50 mg, 0.094 mmol) in DMSO (2.0 mL) were added ethylenediamine (6.4 uL, 0.095 mmol), HATU (39.5 mg, 0.104 mmol), Hunigs base (50 |xL, 0.282 mmol), and the mixture was stirred at room temperature until the starting material was consumed. Additional product from Example IE (50 mg, 0.094 mmol), HATU (39.5 mg, 0.104 mmol), and Hunigs base (50 uL, 0.282 mmol) were added and the reaction was stirred for 2 hours. The reaction was diluted with ethyl acetate and washed with HC1 (aq. 1M). Dried over Na2S04, filtered and evaporated. Purification by chromatography on silica gel eluting with (4% to 7% methanol in dichloromethane) gave the title compound (100 mg, 91 % yield) as a light yellow solid. !H NMR (500 MHz, DMSO-D6) 5 pptn 1.32 (d, J=6.87 Hz, 12 H) 1.46 (s, 18 H) 3.39 (s, 4 H) 6.94 (d, J=8.09 Hz, 2 H) 7.30 (d, J=8.70 Hz, 4 H) 7.48 (d, J=8.54 Hz, 4 H) 7.59 (d, J=8.09 Hz, 2 H) 7.66 (d, J=8.09 Hz, 2 H) 7.84 (s, 2 H) 8.54 (s, 2 H) 8.56 (s, 2 H) 8.81 (d, J=8.39 Hz, 2 H) 9.53 (s, 2 H) 10.12 (s, 2 H). MS (ESI) m/z 1088 (M + H)+. N,N'-(ethane-l,2-diyl)bis(4-(4-aminophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4- ylamino)benzamide) The product from Example 5A was dissolve in dichloromethane (2.0 mL) and TFA (2.0 mL) - and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated and NH4OH was added and the mixture was evaporated to dryness. Purification by prep TLC (10% methanol in dichloromethane) gave the title compound (28 mg, 36% yield) as a yellow solid. JH NMR (300 MHz, DMSO-D6) 5 ppm 1.32 (d, J=6.99 Hz, 12 H) 5.55 (s, 4 H) 6.60 (d, J=8.46 Hz, 4 H) 6.75 (d, J=8.09 Hz, 2 H) 7.10 (d, J=8.46 Hz, 4 H) 7.57 (s, 4 H) 7.76 (s, 2 H) 8.50 (s, 4 H) 8.80 (d, J=5.52 Hz, 2 H). MS (ESI) m/z 888 (M + H)+. To a solution of the product from Example IE (100 mg, 0.188 mmol) in DMSO (2.0 mL) were added piperazine (16 mg, 0.188 mmol), HATU (79 mg, 0.207 mmol) and Hunigs base (100 |xL, 0.564 mmol) and the mixture was stirred at room temperature until the starting material was consumed. Additional product from Example IE (100 mg, 0.188 mmol), HATU (79 mg, 0.212 mmol), and Hunigs base (100 nL, 0.564 mmol), were added and the reaction was stirred for 2 hours. The reaction was diluted with ethyl acetate and washed water. Dried over Na2S04, filtered and evaporated. Purification by chromatography on silica gel ehrting with (10% methanol in dichloromethane) gave the title compound (150 mg) as a yellow solid. To a solution of the product from Example 6A (20 mg, 0.033 mmol) in DMF (1.0 mL) and pyridine (1.0 mL) were added EDAC (32 mg, 0.167 mmol) and the product from Example IE (17.7 mg, 0.033 mmol) and the mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was suspended in methanol. The solid was collected using centrifugation gave the title compound (22 mg, 57% yield). Example 6C piperazine-l,4-diylbis((4-(4-aminophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4- ylamino)phenyl)methanone) The product from Example 6B was dissolved in TFA (1.0 mL) and dichloromethane (1.0 mL) and the mixture was then allowed to stir at room temperature for 1 hour. The solvent was evaporated and NH4OH was added and the mixture was evaporated to dryness. Purification by precipitation from methanol gave the title compound (12 mg, 94% yield) as a yellow solid. XH NMR (300 MHz, DMSO- D6) § ppm 1.32 (d, J=6.62 Hz, 12 H) 3.14 - 3.24 (m, 2 H) 3.54 (s, 8 H) 5.60 (s, 4 H) 6.61 (d, J=8.46 Hz, 4 H) 6.79 (d, J=5.15 Hz, 2 H) 7.13 (d, J=8.46 Hz, 4 H) 7.23 (s, 2 H) 7.41 (s, 2 H) 7.61 (d, J=6.99 Hz, 2 H) 8.56 (s, 2 H) 8.84 (d, J=6.25 Hz, 2 H) 10,11 (s, 2 H). MS (ESI) m/z 914 (M + H)+. Example 7 N-(4-(4-ammophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)phenyl)-3-(7- isopropy lpyrido [2,3 -d]pyrimidin-4-ylamino)benzamide To methyl 3-aminobenzoate (0.50 g, 3.31 mmol) in acetic acid (10 mL) was added (E)-N'-(3- cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamide (0.71 g, 3.31 mmol) and the mixture was stirred at 120 °C for 25 minutes. Reaction mixture was cooled to room temperature and a solid formed. Water was added and solid was collected by filtration. Purification by chromatography on silica gel eluting with 0-30% methanol in dichloromethane gave the title compound (1.05 g, 98% yield). temperature overnight. Reaction was neutralized with 1 N HC1 and extracted with ethyl acetate. Dried over Na2S04, filtered and concentrated to give the title compound (1.5 g). To a solution of the product from Example 7B (25.8 mg, 0.084 mmol) in DMSO (2.0 mL) were added the product from Example 2A (40 mg, 0.084 mmol), HATU (31.8 mg, 0.084 mmol), and Hunigs base (56 uL, 0.318 mmol), and the mixture was stirred at room temperature for 24 hours. Additional HATU (39.5 mg, 0.104 mmol), and Hunigs base (50 \xL, 0.282 mmol) were added and the reaction was stirred for 48 hours. Added more HATU (39.5 mg, 0.104 mmol) and heated at 45 °C for 8 hours. Added more HATU (39.5 mg, 0.104 mmol) and stirred overnight at room temperature. Water was added and the product was collected by filtration. Purification by chromatography on silica gel eluting with (0% to 5% methanol in dichloromethane) gave the title compound (40 mg, 63% yield). Example 7D N-(4-(4-aminophenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)phenyl)-3-(7- isopropylpyrido[2,3-d]pyrimidin-4-ylamino)benzamide The product from Example 7C (40 mg, 0.050 mmol) was dissolved in dioxanc (2.0 mL) and 4M HC1 in dioxane (0.25 mL) was added. This solution was stirred at room temperature overnight. The solid HC1 salt of the product was filtered off then dissolved in methanol and added to saturated NaHCC>3. Extracted with ethyl acetate and evaporated. Purification by chromatography on silica gel eluting with (0% to 30% methanol in dichloromethane) gave the title compound (13 mg, 37% yield). lH NMR (300 MHz, DMSO-D6) d ppm 1.36 (dd, 7=6.80, 4.23 Hz, 12 H) 3.20 - 3.30 (m, 2 H) 6.57 (d, .7=8.46 Hz, 2 H) 7.04 - 7.12 (m, 3 H) 7.60 - 7.70 (m, 2 H) 7.82 - 7.95 (m, 3 H) 8.00 - 8.08 (m, 2 H) 8.29 (s, 1 H) 8.83 - 8.93 (m, 2 H) 9.09 (d, J=12.50 Hz, 1 H) 9.17 (d, J=7.72 Hz, 1 H) 10.58 (s, 1 H) 11.3 8 (s, 1 H) 11.69 (s, 1 H). MS (ESI) m/z 693 (M + H)+. The title compound can be prepared by first coupling l-fluoro-4-iodo-2-nitrobenzene with ethynyltrimethylsilane by Sonogashira reaction using a suitable catalyst. Pd catalysts such as Pd(PPh3)4 or Pd(dppf)Cl2 may be employed or generated in situ using a Pd (II) catalyst such Pd(OAc)2 or Pd2(dba)3 and organophosphorous ligands, such as PPI13 or P(t-Bub. Alternatively, a Cu (I) catalyst may be employed, such as Cu (I) iodide. Reactions may be conducted with addition of a base such K2CC>3 or K3PO4 or an amine base such as triethylamine or Hunig's base in a solvent such as THF or DMF. The trimethylsilyl (TMS) protecting group may be removed using a base such as K2CO3 in a solvent such as methanol or THF to produce 4-ethynyl-l-fluoro-2-nitrobenzene. A second Sonogashira reaction between l-fluoro-4-iodo-2-nitrobenzene and 4-ethynyl-l-fluoro-2-nitrobenzene may be conducted under the analogous conditions to the first coupling to form l,2-bis(4-fiuoro-3- nitrophenyl)ethyne. Couplings may be conducted concurrently to give symmetric products or sequentially to give non-symmetric products. The fluoride and nitro substituted product may be reacted with alkyl, aryl, or heteroaryl alcohols, thiols, phenols, or thiophenols using a base such as K2CO3 or Hunig's base in a solvent such as THF or DMF. Nitro groups may be reduced to amino groups, using Pd or Raney Ni catalyzed hydrogenation or using Fe in the presence of NH4CI, HC1, or acetic acid, and further functionalized to the title compound using the processes described in U.S. Patent Application Publication Nos. 20070232627, 20070197558 and 20070232645, and WO2008/133753. Similarly, l-chloro-4-iodo-2-nitrobenzene may be used as the starting material to prepare the title compound of this Example. The following compounds were also prepared according to the processes described herein: The inhibitory activities of the compounds of the present invention can be evaluated using a variety of assays known in the art. For instance, two stable subgenomic replicon cell lines can be used for compound characterization in cell culture: one derived from genotype la-H77 and the other derived from genotype lb-Conl. The replicon constructs can be bicistronic subgenomic replicons. The genotype la replicon construct contains NS3-NS5B coding region derived from the H77 strain of HCV (la-H77). The replicon also has a firefly luciferase reporter and a neomycin phosphotransferase (Neo) selectable marker. These two coding regions, separated by the FMDV 2a protease, comprise the first cistron of the bicistronic replicon construct, with the second cistron containing the NS3-NS5B coding region with addition of adaptive mutations. The lb-Conl replicon construct is identical to the la-H77 replicon, except that the NS3-NS5B coding region is derived from the lb-Conl strain and that the replicon contains different adaptive mutations. Replicon cell lines can be maintained in Dulbecco's modified Eagles medium (DMEM) containing 10% (v/v) fetal bovine serum (FBS), 100 IU/ml penicillin, 100 mg/ml streptomycin (Invitrogen), and 200 mg/ml G418 (Invitrogen). The inhibitory effects of the compounds of the invention on HCV replication can be determined by measuring activity of the luciferase reporter gene. For example, rcplicon-containing cells can be seeded into 96 well plates at a density of 5000 cells per well in 100 ul DMEM containing 5% FBS. The following day compounds can be diluted in dimethyl sulfoxide (DMSO) to generate a 200x stock in a series of eight half-log dilutions. The dilution series can then be further diluted 100-fold in the medium containing 5% FBS. Medium with the inhibitor is added to the overnight cell culture plates already containing 100 ul of DMEM with 5% FBS. In. assays measuring inhibitory activity in the presence of human plasma, the medium from the overnight cell culture plates can be replaced with DMEM containing 40% human plasma and 5% FBS. The cells can be incubated for three days in the tissue culture incubators and are then lysed for RNA extraction. For the luciferase assay, 30 ul of Passive Lysis buffer (Promega) can be added to each well, and then the plates are incubated for 15 minutes with rocking to lyse the cells. Luciferin solution (100 ul, Promega) can be added to each well, and luciferase activity can be measured with a Victor II luminometer (Perkin- Elmer). The percent inhibition of HCV RNA replication can be calculated for each compound concentration and the IC50 and/or EC50 value can be calculated using nonlinear regression curve fitting to the 4-parameter logistic equation and GraphPad Prism 4 software. When evaluated using the above method, representative compounds of the present invention inhibited HCV replicon replication with IC50 values in the range of from about 0.1 nM to about 100 uM. IC50 refers to 50% inhibitory concentration. Cytotoxicity of the compounds of the present invention can also be evaluated using methods known in the art. When tested, the TC50 values of representative compounds of the present invention were often greater than the corresponding IC50 values of the compounds. TC50 refers to 50% toxicity concentration. Table 6 lists the IC50 values of the compounds of Examples 1-28 when tested using HCV Teplicons. The present invention also features pharmaceutical compositions comprising the compounds of the invention. A pharmaceutical composition of the present invention can comprise one or more compounds of the invention, each of which has a formula independently selected from selected from Formulae I, II or III. In addition, the present invention features pharmaceutical compositions comprising pharmaceutical^ acceptable salts, solvates, or prodrugs of the compounds of the invention. Without limitation, pharmaceutically acceptable salts can be zwitterions or derived from pharmaceutically acceptable inorganic or organic acids or bases. Preferably, a pharmaceutically acceptable salt retains the biological effectiveness of the free acid or base of the compound without undue toxicity, irritation, or allergic response, has a reasonable benefit/risk ratio, is effective for the intended use, and is not biologically or otherwise undesirable. The present invention further features pharmaceutical compositions comprising a compound of the invention (or a salt, solvate or prodrug thereof) and another therapeutic agent. By way of illustration not limitation, these other therapeutic agents can be selected from antiviral agents (e.g., anti-HIV agents, anti-HBV agents, or other anti-HCV agents such as HCV protease inhibitors, HCV polymerase inhibitors, HCV helicase inhibitors, IRES inhibitors or NS5A inhibitors), anti-bacterial agents, anti-fungal agents, imniunomodulators, anti-cancer or chemotherapeutic agents, anti- inflammation agents, antisense RNA, siRNA, antibodies, or agents for treating cirrhosis or inflammation of the liver. Specific examples of these other therapeutic agents include, but are not limited to, ribavirin, a-interferon, (3-interferon, pegylated interferon-a, pegylated interferon-lambda, ribavirin, viramidine, R-5158, nitazoxanide, amantadine, Debio-025, NIM-811, R7128, R1626, R4048, T-l 106, PSI-7851, PF-00868554, ANA-598, IDX184, IDX102, IDX375, GS-9190, VCH-759, VCH-916, MK-3281, BCX-4678, MK-3281, VBY708, ANA598, GL59728, GL60667, BMS-790052, BMS-791325, BMS-650032, GS-9132, ACH-1095, AP-H005, A-831, A-689, AZD2836, telaprevir, boceprevir, ITMN-191, BI-201335, VBY-376, VX-500 (Vertex), PHX-B, ACH-1625, IDX136, IDX316, VX-813 (Vertex), SCH 900518 (Schering-Plough), TMC-435 (Tibotec), ITMN-191 (Intermune, Roche), MK-7009 (Merck), IDX-PI (Novartis), BI-201335 (Boehringer Ingelheim), R7128 (Roche), PSI-7851 (Pharmasset), MK-3281 (Merck), PF-868554 (Pfizer), IDX-184 (Novartis), IDX-375 (Pharmasset), B1LB-1941 (Boehringer Ingelheim), GS-9190 (Gilead), BMS-790052 (BMS), Albuferon (Novartis), ritonavir, another cytochrome P450 monooxygenase inhibitor, or any combination thereof. In one embodiment, a pharmaceutical composition of the present invention comprises one or more compounds of the present invention (or salts, solvates or prodrugs thereof), and one or more other antiviral agents. In another embodiment, a pharmaceutical composition of the present invention comprises one or more compounds of the present invention (or salts, solvates or prodrugs thereof), and one or more other anti-HCV agents. For example, a pharmaceutical composition of the present invention can comprise a compounds of the present invention having Formula I, II or III (or (or a salts, solvate or prodrug thereof), and an agent selected from HCV polymerase inhibitors (including nucleoside or non-nucleoside type of polymerase inhibitors), HCV protease inhibitors, HCV helicase inhibitors, CD81 inhibitors, cyclophilin inhibitors, IRES inhibitors, or NS5A inhibitors. In yet another embodiment, a pharmaceutical composition of the present invention comprises one or more compounds of the present invention (or salts, solvates or prodrugs thereof), and one or more other antiviral agents, such as anti-HBV, anti-HIV agents, or anti-hepatitis A, anti-hepatitis D, anti-hepatitis E or anti-hepatitis G agents. Non-limiting examples of anti-HBV agents include adefovir, lamivudine, and tenofovir. Non-limiting examples of anti-HIV drugs include ritonavir, lopinavir, indinavir, nelfinavir, saquinavir, amprenavir, atazanavir, tipranavir, TMC-114, fosamprenavir, zidovudine, lamivudine, didanosine, stavudine, tenofovir, zalcitabine, abacavir, efavirenz, nevirapine, delavirdine, TMC-125, L-870812, S-1360, enfuvirtide, T-1249, or other HIV protease, reverse transcriptase, integrase or fusion inhibitors. Any other desirable antiviral agents can also be included in a pharmaceutical composition of the present invention, as appreciated by those skilled in the art. A pharmaceutical composition of the present invention typically includes a pharmaceutically acceptable carrier or excipient. Non-limiting examples of suitable pharmaceutically acceptable carriers/excipients include sugars (e.g., lactose, glucose or sucrose), starches (e.g., com starch or potato starch), cellulose or its derivatives (e.g., sodium carboxymethyl cellulose, ethyl cellulose or cellulose acetate), oils (e.g., peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil or soybean oil), glycols (e.g., propylene glycol), buffering agents (e.g., magnesium hydroxide or aluminum hydroxide), agar, alginic acid, powdered tragacanth, malt, gelatin, talc, cocoa butter, pyrogen-free water, isotonic saline, Ringer's solution, ethanol, or phosphate buffer solutions. Lubricants, coloring agents, releasing agents, coating agents, sweetening, flavoring or perfuming agents, preservatives, or antioxidants can also be included in a pharmaceutical composition of the present invention. The pharmaceutical compositions of the present invention can be formulated based on their routes of administration using methods well known in the art. For example, a sterile injectable preparation can be prepared as a sterile injectable aqueous or oleagenous suspension using suitable dispersing or wetting agents and suspending agents. Suppositories for rectal administration can be prepared by mixing drugs with a suitable nonirritating excipient such as cocoa butter or polyethylene glycols which are solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and release the drugs. Solid dosage forms for oral administration can be capsules, tablets, pills, powders or granules. In such solid dosage forms, the active compounds can be admixed with at least one inert diluent such as sucrose lactose or starch. Solid dosage forms may also comprise other substances in addition to inert diluents, such as lubricating agents. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral administration can include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or elixirs containing inert diluents commonly used in the art. Liquid dosage forms may also comprise wetting, emulsifying, suspending, sweetening, flavoring, or perfuming agents. The pharmaceutical compositions of the present invention can also be administered in the form of liposomes, as described in U.S. Patent No. 6,703,403. Formulation of drags that are applicable to the present invention is generally discussed in, for example, Hoover, John E., REMINGTON'S PHARMACEUTICAL SCIENCES (Mack Publishing Co., Easton, PA: 1975), and Lachman, L., eds., PHARMACEUTICAL DOSAGE FORMS (Marcel Decker, New York, N.Y., 1980). Any compound described herein, or a pharmaceutically acceptable salt thereof, can be used to prepared pharmaceutical compositions of the present invention. The present invention further features methods of using the compounds of the present invention (or salts, solvates or prodrugs thereof) to inhibit HCV replication. The methods comprise contacting cells infected with HCV virus with an effective amount of a compound of the present invention (or a salt, solvate or prodrug thereof), thereby inhibiting the replication of HCV virus in the cells. As used herein, "inhibiting" means significantly reducing, or abolishing, the activity being inhibited (e.g., viral replication). In many cases, representative compounds of the present invention can reduce the replication of HCV virus (e.g., in an HCV replicon assay as described above) by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or more. The compounds of the present invention may inhibit all HCV subtypes. Examples of HCV subtypes that are amenable to the present invention include, but are not be limited to, HCV genotypes 1, 2, 3, 4, 5 and 6, including HCV genotypes la, lb, 2a, 2b, 2c or 3a. In one embodiment, a compound or compounds of the present invention (or salts, solvates or prodrugs thereof) are used to inhibit the replication of HCV genotype la. In another embodiment, a compound or compounds of the present invention (or salts, solvates or prodrugs thereof) are used to inhibit the replication of HCV genotype lb. In still another embodiment, a compound or compounds of the present invention (or salts, solvates or prodrugs thereof) are used to inhibit the replication of both HCV genotypes la and lb. The present invention also features methods of using the compounds of the present invention (or salts, solvates or prodrugs thereof) to treat HCV infection. The methods typically comprise administering a therapeutic effective amount of a compound of the present invention (or a salt, solvate or prodrug thereof), or a pharmaceutical composition comprising the same, to an HCV patient, thereby reducing the HCV viral level in the blood or liver of the patient. As used herein, the term "treating" refers to reversing, alleviating, inhibiting the progress of, or preventing the disorder or condition, or one or more symptoms of such disorder or condition to which such term applies. The term "treatment" refers to the act of treating. In one embodiment, the methods comprise administering a therapeutic effective amount of two or more compounds of the present invention (or salts, solvates or prodrugs thereof), or a pharmaceutical composition comprising the same, to an HCV patient, thereby reducing the HCV viral level in the blood or liver of the patient. A compound of the present invention (or a salt, solvate or prodrug thereof) can be administered as the sole active pharmaceutical agent, or in combination with another desired drug, such as other anti-HCV agents, anti-HIV agents, anti-HBV agents, anti-hepatitis A agents, anti- hepatitis D agents, anti-hepatitis E agents, anti-hepatitis G agents, or other antiviral drugs. Any compound described herein, or a pharmaceutically acceptable salt thereof, can be employed in the methods of the present invention. A compound of the present invention (or a salt, solvent or prodrug thereof) can be administered to a patient in a single dose or divided doses. A typical daily dosage can range, without limitation, from 0.1 to 200 mg/kg body weight, such as from 0.25 to 100 mg/kg body weight. Single dose compositions can contain these amounts or submultiples thereof to make up the daily dose. Preferably, each dosage contains a sufficient amount of a compound of the present invention that is effective in reducing the HCV viral load in the blood or liver of the patient. The amount of the active ingredient, or the active ingredients that are combined, to produce a single dosage form may vary depending upon the host treated and the particular mode of administration. It will be understood that the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination, and the severity of the particular disease undergoing therapy. The present invention further features methods of using the pharmaceutical compositions of the present invention to treat HCV infection. The methods typically comprise administering a pharmaceutical composition of the present invention to an HCV patient, thereby reducing the HCV viral level in the blood or liver of the patient. Any pharmaceutical composition described herein can be used in the methods of the present invention. In addition, the present invention features use of the compounds or salts of the present invention for the manufacture of medicaments for the treatment of HCV infection. Any compound described herein, or a pharmaceutically acceptable salt thereof, can be used to make medicaments of the present invention. The foregoing description of the present invention provides illustration and description, but is not intended to be exhaustive or to limit the invention to the precise one disclosed. Modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. Thus, it is noted that the scope of the invention is defined by the claims and their equivalents. CLAIMS What is claimed is: 1. A compound of Formula I, or a pharmaceutic ally acceptable salt thereof, wherein: Ai is C5-C10carbocyclyl or 5- to 10-membered heterocyclyl, and is substituted with -X1-R7, wherein said C5-C10carbocyclyl and 5- to 10-membered heterocyclyl are optionally substituted with one or more RA; A2 is C5-C10carbocyclyl or 5- to 10-membered heterocyclyl, and is substituted with -X2-R8, wherein said C5-Ci0carbocyclyl and 5- to 10-membered heterocyclyl are optionally substituted with one or more RA; X[ and X2 are each independently selected from a bond, -Ls-, -O-, -S-, or -N(RB)-; R7 and Rg are each independently selected from hydrogen, -LA, C5-C10carbocyclyl, or 5- to 10- membered heterocyclyl, wherein at each occurrence said C5-C10carbocyclyl and 5- to 10- membered heterocyclyl are each independently optionally substituted with one or more RA; Z1 and Z2 are each independently selected from a bond, -C(RcRc-) -O-, -S-, or -N(RB)-; Wi, W2, W3, and W4 are each independently selected from N or C(RD), wherein RD is independently selected at each occurrence from hydrogen or RA; R1 and R2 are each independently selected from hydrogen or RA; R3 and R4 are each independently selected from hydrogen or RA; or R3 and R4, taken together with the carbon atoms to which they are attached, form a C5-C10carbocyclic or 5- to 10-membered heterocyclic ring, wherein said C5-C10carbocyclic and 5- to 10-membered heterocyclic ring are optionally substituted with one or more RA; R5 and R6 are each independently selected from hydrogen or RA; or R5 and R&, taken together with the carbon atoms to which they are attached, form a C5-C10carbocyclic or 5- to 10-membered heterocyclic ring, wherein said C5-C10carbocyclic and 5- to 10-membered heterocyclic ring are optionally substituted with one or more RA; T is selected from a bond, -Ls-, -Ls-M-Ls-, -Lg-M-Lg—M'-Ls—, wherein M and M' are each independently selected from a bond, -O-, -S- -N(RB)-, -C(O)-, -S(O)2-, -S(O)-, -OS(O)- -OS(O)2- -S(O)20-, -S(O)O-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(RB)-, - N(RB)C(O)-, -N(RB)C(O)O-, -OC(O)N(RB)-, -N(RB)S(O)- -N(RB)S(O)2- -S(O)N(RB)- - S(O)2N(RB)-, -C(O)N(RB)C(O)-, -N(RB)C(O)N(RB.)- -N(RB)S02N(RB.)-, - N(RB)S(O)N(RB)-, C5-Cl0carbocycle, or 5- to 10-membered hcterocycle, and wherein T is optionally substituted with one or more RA; RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl, cyano, -LA, or -LS-RE; RB and RB- are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2- C6alkenyl, CrCgalkynyl, C3-Cecarbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6-membered heterocyclyl, or (3- or 6-membered heterocyclyl)C1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; Re and Re are each independently selected at each occurrence from hydrogen; halogen; hydroxy; mercapto; amino; carboxy; nitro; phosphate; oxo; thioxo; formyl; cyano; or C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, or C3-C6carbocyclyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; LA is independently selected at each occurrence from C1-C6alkyl, C2-C6alkenyl, or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-RS) -S-Rs, -N(RSRS-), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; Ls, Ls> and Ls- are each independently selected at each occurrence from a bond; or Q-Cgalkylene, CrQalkenylene, or Q-Cgalkynylene, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, - N(RsRs')» -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; RE is independently selected at each occurrence from -O-Rs, -S-Rs, -C(O)Rs, -OC(O)Rs, - C(O)ORs, -N(RsRs-), -S(O)Rs, -S02Rs, -C(O)N(RsRs), -N(Rs)C(O)RS', - N(Rs)C(O)N(Rs.RS"), -N(Rs)S02Rs., -SO2N(RsRs0, -N(Rs)S02N(Rs-Rs"), - N(Rs)S(O)N(Rs.Rs..), -OS(O)-Rs, -OS(O)2-Rs, -S(O)2ORs, -S(O)ORs, -OC(O)ORs, - N(Rs)C(O)ORS', -OC(O)N(RsRs), -N(Rs)S(O)-Rs-, -S(O)N(RsRs-), -C(O)N(Rs)C(O)-Rs-, C3-C6carbocyclyl, or 3- to 6-membered heterocyclyl, and said C3-C6carbocyclyl and 3- to 6- membered heterocyclyl are each independently optionally substituted at each occurrence with one or more substituents selected from Rs (except hydrogen), halogen, -O-RB, -S-RB, - N(RBRB')5 -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano; and Rs, Rs' and Rs- are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2-C6allcenyl, C2-C6alkynyl, C3-C6carbocyclyl, C5-QcarbocyclylC1-Ccalkyl, 3- to 6- membered heterocyclyl, or (3- to 6-membered heterocyclyl)CrC6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-RB, -S-RB, -N(RBRB), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano. 2. The compound or salt of claim 1, wherein: A1 is C5-C6carbocyclyl or 5- to 6-membered heterocyclyl, and is substituted with -Xi-R7, wherein said C5-C6carbocyclyl and 5- to 6-membered heterocyclyl are optionally substituted with one or more RA; A2 is C5-C6carbocyclyl or 5- to 6-membered heterocyclyl, and is substituted with -X2-R8, wherein said C5-C6carbocyclyl and 5- to 6-membered heterocyclyl are optionally substituted with one or more RA; R3 and R4 are each independently selected from hydrogen or RA; or R3 and R4, taken together with the carbon atoms to which they are attached, form a C5-C6scarbocyclic or 5- to 6-membered heterocyclic ring, wherein said C5-C6carbocyclic and 5- to 6-membered heterocyclic ring are optionally substituted with one or more RA; and R5 and R6 are each independently selected from hydrogen or RA; or R5 and R& taken together with the carbon atoms to which they are attached, form a C5-Cecarbocyclic or 5- to 6-membered heterocyclic ring, wherein said C5-C6carbocyclic and 5- to 6-membcTed heterocyclic ring are optionally substituted with one or more RA. 3. The compound or salt according to one of claims 1-2, wherein at least one of R7 and Rg is C5- C6carbocyclyl or 5- to 6-membered heterocyclyl, and is optionally substituted with one or more RA. 4. The compound or salt according to one of claims 1-2, wherein said at least one of R7 and Rs is phenyl, and is optionally substituted with one or more RA. 5. The compound or salt according to one of claims 1-2, wherein R7 and Rs are independently selected from C5-C6carbocyclyl or 5- to 6-membered heterocyclyl, and at each occurrence said C5- C6carbocyclyl and 5- to 6-membered heterocyclyl are each independently optionally substituted with one or more RA. 6. The compound or salt according to one of claims 1-2, wherein R7 and R» arc phenyl, and are each independently optionally substituted with one or more RA. 7. The compound or salt according to one of claims 1-2, wherein A1 and A2 are phenyl, and are each independently optionally substituted with one or more RA. 8. The compound or salt according to one of claims 1-7, wherein Wb W2, W3 and W4 are N, and Z1 and Z2 are independently -N(RB)-. 10. The compound or salt of claim 9, wherein: W1,W2,W3 and W4 are N; Zi and Z2 are independently -N(RB)-; and at least one of X1 and X2 is -CH2-, -O-, or -S-. 11. The compound or salt of claim 9, wherein W1,W2,W3 and W4 are N; Z\ and Z2 are -NH-; at least one of Xj and X2 is -CH2-, -O-, or -S-; at least one of R7 and R8 is phenyl, and is optionally substituted with one or moTe RA; Ri and R2 are hydrogen; R9, Rio, R11, R12, R13, and R14 are each independently selected from hydrogen; halogen; or d- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, or C3-C6carbocyclyC1-Csallcyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano. 12. The compound or salt of claim 9, wherein W1,W2, W3 and W4 are N; Z1 and Z2 are -NH-; X1 and X2 are each independently selected from -CH2-,-O-, or -S-; R7 and Rg are phenyl and are each independently optionally substituted with one or more RAJ R1 and R2 are hydrogen; R9, R10, Rn, R12, R13, and R14 are each independently selected from hydrogen; halogen; or C1- Qalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, or C5-C6carbocyclyC1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano. wherein: Xi and X2 are each independently selected from a bond, -Ls-, -O-, -S-, or -N(RB)-; R7 and R8 are each independently selected from hydrogen, -LA, C5-C10carbocyclyl, or 5- to 10- membered heterocyclyl, wherein at each occurrence said C5-C10carbocyclyl and 5- to 10- membered heterocyclyl are each independently optionally substituted with one or more RA; Z1 and Z2 are each independently selected from a bond, -C(RcRc)_5 -O-, ~S-, or -N(RB)-; W1, W2, W3, W4, W5, W6, W7, and W8 are each independently selected from N or C(RD), wherein RD is independently selected at each occurrence from hydrogen or RA; R1, R2, R9, R11, R12, R14, R15, and R16 are each independently selected at each occurrence from hydrogen or RA; m and n are each independently selected from 0, 1,2, or 3; T is selected from a bond, -Ls-, —Ls-M-Ls—, -Lg-M-Lg—M'-Lg»-, wherein M and M' are each independently selected from a bond, -O-, -S-, -N(RB)-, -C(O)-, -S(O)2-, -S(O)-, -OS(O)-, -OS(O)2-, -S(O)20-, -S(O)O- -C(O)O- -OC(O)-, -OC(O)O-, -C(O)N(RB)- - N(RB)C(O)- -N(RB)C(O)O- -OC(O)N(RB)-, -N(RB)S(O)-, -N(RB)S(O)2- -S(O)N(RB)- - S(O)2N(RB)-, -C(O)N(RB)C(O)-, -N(RB)C(O)N(RB.)-, -N(RB)S02N(RB>)-, - N(RB)S(O)N(RB')-, C5-Ci0carbocycle, or 5- to 10-membered heterocycle, and wherein T is optionally substituted with one or more RA; RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl, cyano, -LA, or -LS-RE; RB and RB' are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, C5-CecarbocyclylC1-Cealkyl, 3- to 6-membered heterocyclyl, or (3- or 6-membered heterocyclyl)C1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; Re and Re are each independently selected at each occurrence from hydrogen; halogen; hydroxy; mercapto; amino; carboxy; nitro; phosphate; oxo; thioxo; formyl; cyano; or C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, or C3-C6carbocyclyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; LA is independently selected at each occurrence from CrC6alkyl, C2-C6alkenyl, or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, -N(RsRsO, -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; Ls, Ls- and Ls- are each independently selected at each occurrence from a bond; or d-C6alkylene, C2-C6alkenylene, or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, - N(RsRs), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; RE is independently selected at each occurrence from -O-Rs, -S-Rs, -C(O)Rs, -OC(O)Rs, - C(O)ORs, -N(RSRS.), -S(O)Rs, -S02Rs, -C(O)N(RsRs), -N(Rs)C(O)Rs., - N(Rs)C(O)N(Rs-Rs..), -N(Rs)SO2Rs', -SO2N(RsRs0, -N(Rs)S02N(Rs.Rs"), N(Rs)S(O)N(Rs.Rs-), -OS(O)-Rs, -OS(O)2-Rs, -S(O)2ORS, -S(O)ORs, -OC(O)ORs, - N(Rs)C(O)ORs-, -OC(O)N(RsRs-), -N(Rs)S(O)-Rs., -S(O)N(RsRs-), -C(O)NCRs)C(O)-Rs-, C3-C6carbocyclyl, or 3- to 6-membered heterocyclyl, and said C3-C6carbocyclyl and 3- to 6- membered heterocyclyl are each independently optionally substituted at each occurrence with one or more substituents selected from Rs (except hydrogen), halogen, -O-RB, -S-RB, - N(RBRB'), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano; and Rs, Rs' and Rs" are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6- membered heterocyclyl, or (3- to 6-membered heterocyclyl)C1-C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-RB, -S-RB, -N(RBRB.), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano. 14. The compound or salt of claim 13, wherein: at least one of X1 and X2 is selected from -CH2-, -O-, or -S-; at least one of R7 and Rg is selected from C5-C6carbocyclyl or 5- to 6-membered heterocyclyl, wherein said C5-C6carbocyclyl and 5- to 6-membered heterocyclyl are optionally'substituted with one or more RA; and Z1 and Z2 are each independently -N(RB)-. 15. The compound or salt according to one of claims 13-14, wherein: X1 and X2 are each independently selected from -CH2- -O-, or -S-; R7 and Rg are each independently selected from C5-Cecarbocyclyl or 5- to 6-membered heterocyclyl, wherein at each occurrence said C3-C6carbocyclyl and 5- to 6-membered heterocyclyl are each optionally substituted with one or more RA; and Z1 and Z2 are each independently -N(RB)-. 16. The compound or salt according to one of claims 13-15, wherein: Wi, W2, W3, W4, W5, and W7 are N, and W6 and W8 are each independently C(RD); Ri and R2 are hydrogen; R7 and R8 are phenyl, and are each independently optionally substituted with one or more RA; and R9, Rn, R12, R14, and RD are each independently selected at each occurrence from hydrogen; halogen; or C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, or C5-C6carbocyclyC1- C6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano. 17. A compound of Formula HI, or a pharmaceutically acceptable salt thereof, wherein: X1 and X2 are each independently selected from a bond, -Ls-, -O-, -S-, or -N(RB)-; R7 and R8 are each independently selected from hydrogen, -LA, C5-CmcarbocyclyL or 5- to 10- membered heterocyclyl, wherein at each occurrence said C5-C10carbocyclyl and 5- to 10- membered heterocyclyl are each independently optionally substituted with one or more RA; Z1 and Z2 are each independently selected from a bond, -C(RcRc)-> -O-, -S-, or -N(RB)-; W1, W2, W3, W4, W5, W6, W7, and Wg are each independently selected from N or C(RD), wherein RD is independently selected at each occurrence from hydrogen or RA; Rl, R2, R9, R11, R12, R14, R15, and Ri6 are each independently selected at each occurrence from hydrogen or RA; m and n are each independently selected from 0,1,2, or 3; T is selected from a bond, -Ls-, -Ls-M-Ls—, -Ls-M-Ls.-M'-Ls—, wherein M and M' are each independently selected from a bond, -O-, -S-, -N(RB)- -C(O)-, -S(O)2- -S(O)-, -OS(O)- -OS(O)2- -S(O)20-, -S(O)O-, -C(O)O- -OC(O)-, -OC(O)O-, -C(O)N(RB)-, - N(RB)C(O)- -N(RB)C(O)O-, -OC(O)N(RB)- -N(RB)S(O)-, -N(RB)S(O)2-, -S(O)N(RB)-, - S(O)2N(RB)- -C(O)N(RB)C(O)-, -N(RB)C(O)N(RB.)-, -N(RB)S02N(RB.)- - N(RB)S(O)N(RB-)-, C5-C10carbocycle, or 5- to 10-membered heterocyele, and wherein T is optionally substituted with one or more RA; RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl, cyano, -LA, or -Ls-RE; RB and RB' are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2- C6alkenyl, C1-C6alkynyl, C3-C6carbocyclyl, C5-CgcarbocyclylC1-Ceallcyl, 3- to 6-membered heterocyclyl, or (3- or 6-membered heterocyclyl)C1-Csalkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; Rc and Rc are each independently selected at each occurrence from hydrogen; halogen; hydroxy; mercapto; amino; carboxy; nitro; phosphate; oxo; thioxo; formyl; cyano; or CrC6alkyl, C2- C6alkenyl, C2-C6alkynyl, or C3-C6carbocyclyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, phosphate, oxo, thioxo, formyl or cyano; LA is independently selected at each occurrence from C1-Csalkyl, C2-C6alkenyl, or C2-Csalkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, -N(RsRs-), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; Ls, Ls- and Ls- are each independently selected at each occurrence from a bond; or Q-Cealkylene, C2-C6alkcnylcnc, or Cz-Csalkynylcnc, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-Rs, -S-Rs, - N(RsRs'), -OC(O)Rs, -C(O)ORs, nitro, phosphate, oxo, thioxo, formyl or cyano; RE is independently selected at each occurrence from -O-Rg, -S-Rs, -C(O)Rs, -OC(O)Rs, - C(O)ORs, -N(RsRs-), -S(O)Rs, -S02Rs, -C(O)N(RsRs.), -N(Rs)C(O)Rs., - N(Rs)C(O)N(Rs-Rs"). -N(Rs)S02RS', -SO2N(RsRs0, -N(Rs)S02N(Rs-Rs»), N(Rs)S(O)N(Rs.RS"), -OS(O)-Rs, -OS(O)2-Rs, -S(O)2ORs, -S(O)ORs, -OC(O)ORs, - N(Rs)C(O)ORs<, -OC(O)N(RsRs), -N(Rs)S(O)-Rs., -S(O)N(RsRs.), -C(O)N(Rs)C(O)-Rs., C3-C6carbocyclyl, or 3- to 6-membered heterocyclyl, and said C3-C6carbocyclyl and 3- to 6- membered heterocyclyl are each independently optionally substituted at each occurrence with one or more substituents selected from Rs (except hydrogen), halogen, -O-RD, -S-RB, - N(RBRB')> -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano; and Rs, Rs- and Rs- are each independently selected at each occurrence from hydrogen; or C1-Cealkyl, CrQaUcenyl, C2-C6alkynyl, Ca-Cgcarbocyclyl, C3-C6carbocyclylC1-C6alkyl, 3- to 6- membered heterocyclyl, or (3- to 6-membercd hctcrocyclyl)CrC6alkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -O-RB, -S-RB, -N(RBRB-), -OC(O)RB, -C(O)ORB, nitro, phosphate, oxo, thioxo, formyl or cyano. 18. The compound or salt of claim 17, wherein: at least one of X1 and X2 is selected from -CH2-, -O-, or -S-; at least one of R7 and Rs is selected from C5-C6carbocyclyl or 5- to 6-membered heterocyclyl, wherein said C5-C6carbocyclyl and 5- to 6-membered heterocyclyl are optionally substituted - with one or more RA; and Zi and Z2 are each independently -N(RB)-. 19. The compound or salt according to one of claims 17-18, wherein: Xi and X2 are each independently selected from -CH2-, -O-, or -S-; R7 and R3 are each independently selected from C5-C6carbocyclyl or 5- to 6-membered heterocyclyl, wherein at each occurrence said C5-C6carbocyclyl and 5- to 6-membered heterocyclyl are each optionally substituted with one or more RA; and Zt and Z2 are each independently -N(RB)-. 20. The compound or salt according to one of claims 17-19, wherein: W1, W2, W3, W4, W3, and W7 are N, and W6 and W8are each independently C(RD); R1 and R2 are hydrogen; R7 and R8 are phenyl, and are each independently optionally substituted with one or more RA; and R9, R11, R12, R14, and RD are each independently selected at each occurrence from hydrogen; halogen; or C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6carbocyclyl, or C5-CscarbocyclyC1- Cealkyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, ttitro, phosphate, oxo, thioxo, fonnyl or cyano. 21. A pharmaceutical composition comprising a compound or salt according to one of claims 1-20. 22. A method of inhibiting HCV virus replication, comprising contacting cells infected with HCV virus with a compound or salt according to one of claims 1 -20. 23. A method of treating HCV infection, comprising administering to an HCV patient a compound or salt according to one of claims 1-20. 24. A process of making a compound according to one of claims 1-20, comprising a step described in one of schemes described herein. Compounds effective in inhibiting replication of Hepatitis C virus ("HCV") are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

Documents

Application Documents

# Name Date
1 2855-KOLNP-2011-AbandonedLetter.pdf 2018-02-16
1 2855-kolnp-2011-specification.pdf 2011-10-07
2 2855-kolnp-2011-pct request form.pdf 2011-10-07
2 2855-KOLNP-2011-FER.pdf 2017-07-27
3 2855-kolnp-2011-pct priority document notification.pdf 2011-10-07
3 2855-KOLNP-2011-FORM-18.pdf 2012-12-27
4 2855-kolnp-2011-international search report.pdf 2011-10-07
4 2855-KOLNP-2011-(09-01-2012)-CORRESPONDENCE.pdf 2012-01-09
5 2855-kolnp-2011-international publication.pdf 2011-10-07
5 2855-KOLNP-2011-(09-01-2012)-FORM-3.pdf 2012-01-09
6 2855-kolnp-2011-form-5.pdf 2011-10-07
6 2855-KOLNP-2011-(06-01-2012)-CORRESPONDENCE.pdf 2012-01-06
7 2855-kolnp-2011-form-3.pdf 2011-10-07
7 2855-KOLNP-2011-(06-01-2012)-PA-CERTIFIED COPIES.pdf 2012-01-06
8 2855-kolnp-2011-form-2.pdf 2011-10-07
8 2855-KOLNP-2011-(02-01-2012)-ASSIGNMENT.pdf 2012-01-02
9 2855-kolnp-2011-form-1.pdf 2011-10-07
9 2855-KOLNP-2011-(02-01-2012)-CORRESPONDENCE.pdf 2012-01-02
10 2855-kolnp-2011-abstract.pdf 2011-10-07
10 2855-kolnp-2011-description (complete).pdf 2011-10-07
11 2855-kolnp-2011-claims.pdf 2011-10-07
11 2855-kolnp-2011-correspondence.pdf 2011-10-07
12 2855-kolnp-2011-claims.pdf 2011-10-07
12 2855-kolnp-2011-correspondence.pdf 2011-10-07
13 2855-kolnp-2011-abstract.pdf 2011-10-07
13 2855-kolnp-2011-description (complete).pdf 2011-10-07
14 2855-KOLNP-2011-(02-01-2012)-CORRESPONDENCE.pdf 2012-01-02
14 2855-kolnp-2011-form-1.pdf 2011-10-07
15 2855-KOLNP-2011-(02-01-2012)-ASSIGNMENT.pdf 2012-01-02
15 2855-kolnp-2011-form-2.pdf 2011-10-07
16 2855-KOLNP-2011-(06-01-2012)-PA-CERTIFIED COPIES.pdf 2012-01-06
16 2855-kolnp-2011-form-3.pdf 2011-10-07
17 2855-KOLNP-2011-(06-01-2012)-CORRESPONDENCE.pdf 2012-01-06
17 2855-kolnp-2011-form-5.pdf 2011-10-07
18 2855-KOLNP-2011-(09-01-2012)-FORM-3.pdf 2012-01-09
18 2855-kolnp-2011-international publication.pdf 2011-10-07
19 2855-kolnp-2011-international search report.pdf 2011-10-07
19 2855-KOLNP-2011-(09-01-2012)-CORRESPONDENCE.pdf 2012-01-09
20 2855-kolnp-2011-pct priority document notification.pdf 2011-10-07
20 2855-KOLNP-2011-FORM-18.pdf 2012-12-27
21 2855-kolnp-2011-pct request form.pdf 2011-10-07
21 2855-KOLNP-2011-FER.pdf 2017-07-27
22 2855-kolnp-2011-specification.pdf 2011-10-07
22 2855-KOLNP-2011-AbandonedLetter.pdf 2018-02-16

Search Strategy

1 2855kolnp2012_28-06-2017.pdf