Tricyclic fused ring inhibitors of hepatitis c

A compound having formula I:

• wherein:
• D is either present or absent and if present selected from the group consisting of —CR2CR2—, —CR2—, —NRN—, —O— and —S— wherein RN is H, —OH, C1 to C12 alkyl, C1 to C12 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate and sulfonamide and each R is independently selected from the group consisting of hydrogen, —OH, —CN, —NO2, halogen, C1 to C12 alkyl, C1 to C12 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate, sulfonamide and amino;
• A and E are:
• each independently —CR2—, —CR═, —CR2—CR2—, —CR═CR—, —N═CR—, —(CR2)a—N(RN)—(CR2)a—, —(CR2)a—C(O)—N(RN)—(CR2)a—, —(CR2)a—N(RN)—C(O)—(CR2)a— or —(CR2)b—O—(CR2)b—, wherein:
• RN is selected from the group consisting of H, —OH, C1 to C12 alkyl, C1 to C12 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate and sulfonamide;
• each R is independently selected from the group consisting of hydrogen, —OH, —CN, —NO2, halogen, C1 to C12 alkyl, C1 to C12 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate, sulfonamide and amino, wherein:
• two R's either both on a single C or on adjoining C's, together with the C or C's to which they are attached, optionally form a cycle, and
• where two R's are possible on a C, the C may optionally be linked to a single R with a double bond;
• each a and b are independently 0, 1, 2, or 3 with the proviso that if D is present both b's are not 0;
• and
• RN and R may be replaced by a bond to D if D is present,
• if D is absent, A and E can additionally each independently be a bond, —O—, —S—, —S(O2)—, —S(O)—, —C(O)— or —N═, and
• with the proviso that if W and W′ are both 5-membered rings, A and E are either both a bond or both other than a bond;
• each Ra is independently selected from the group consisting of —OH, —CN, —NO2, halogen, C1 to C12 alkyl, C1 to C12 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate, sulfonamide and amino;
• each r is independently 0, 1, 2 or 3;
• W and W′ are each independently selected from the group consisting of
• X1 is CH2, NH, O or S,
• Y1, Y2 and Z1 independently CH or N,
• X2 is NH, O or S,
• W and W′ are each independently optionally substituted with one or more substituents selected from the group consisting of —OH, —CN, —NO2, halogen, C1 to C12 alkyl, C1 to C12 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate, sulfonamide and amino, and
• Cy is a monocyclic, bicyclic or tricyclic 5- to 12-membered cycloalkyl, heterocycle, aryl group or heteroaryl group wherein up to three heteroatoms are independently N, S or O and which is optionally substituted with one or more substituents selected from the group consisting of —OH, —CN, —NO2, halogen, C1 to C12 alkyl, C1 to C12 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate, sulfonamide and amino;
• each Rc, Rd, Re and Rf is independently selected from the group consisting of:
• hydrogen, C1 to C8 alkyl, C1 to C8 heteroalkyl, aralkyl and a 4- to 8-membered ring which may be cycloalkyl, heterocycle, heteroaryl or aryl, wherein,
• each hetero atom, if present, is independently N, O or S,
• each of Rc, Rd, Re and Rf may optionally be substituted by C1 to C8 alkyl, C1 to C8 heteroalkyl, aralkyl, or a 4- to 8-membered ring which may be cycloalkyl, heterocycle, heteroaryl or aryl and wherein each heteroatom, if present, is independently N, O or S,
• Rc and Rd are optionally joined to form a 4- to 8-membered heterocycle which is optionally fused to another 3- to 5-membered heterocycle or heteroaryl ring, and
• Re and Rf are optionally joined to form a 4- to 8-membered heterocycle which is optionally fused to another 3- to 5-membered heterocycle or heteroaryl ring;
• Y and Y′ are each independently carbon or nitrogen;
• and
• Z and Z′ are independently selected from the group consisting of hydrogen, C1 to C8 alkyl, C1 to C8 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, 1-3 amino acids,
• —[U—(CR42)t—NR5—C(R42)t]u—U—(CR42)t—NR7—(CR42)t—R8, —U—(CR42)t—R8, and —[U—(CR42)t—NR5—(CR42)t]u—U—(CR42)t—O—CR42)t—R8, wherein,
• U is selected from the group consisting of —C(O)—, —C(S)— and —S(O)2—,
• each R4, R5 and R7 is independently selected from the group consisting of hydrogen, C1 to C8 alkyl, C1 to C8 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl and aralkyl,
• R8 is selected from the group consisting of hydrogen, C1 to C8 alkyl, C1 to C8 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, —C(O)—R81, —C(S)—R81, —C(O)—O—R81, —C(O)—N—R812, —S(O)2—R81 and —S(O)2—N—R812, wherein each R81 is independently chosen from the group consisting of hydrogen, C1 to C8 alkyl, C1 to C8 heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl and aralkyl,
• optionally, R7 and R8 together form a 4-7 membered ring,
• each t is independently 0, 1, 2, 3, or 4, and
• u is 0, 1, or 2.