US 2014/0371138 A1 · INHIBITORS OF HEPATITIS C VIRUS REPLICATION

A compound having structural formula (I):

and/or a pharmaceutically acceptable salt thereof, wherein:
is
which is substituted by u substituents R1,
each R1 is independently chosen from the group consisting of hydrogen, halogen, —OR3a, —CN, —(CH2)0-6C(O)R3, —CO2R3a, —C(O)N(R3a)2, —SR3a, —S(O)R3a, —S(O2)R3a, —(CH2)0-6N(R3a)2, —N(R3a)SO2R3a, —N(R3a)CO2R3a, —N(R3a)C(O)R3, —N(R3a)COR3a, —N(R3a)C(O)N(R3a), C1-6alkyl, C3-8carbocycle containing from 0 to 3 heteroatoms chosen from N, O and S, and phenyl, and the C1-6alkyl, C3-8carbocycle and phenyl are substituted by from 0 to 3 substitutents independently chosen from the group consisting of hydrogen, halogen, —OR3a, —CN, —CO2R3a, —C(O)N(R3a)2, —N(R3a)2, —N(R3a)CO2R3a, —SR3a, —S(O)R3a, —S(O2)R3a, —N(R3a)SO2R3a, —N(R3a)CO2R3a, —N(R3a)C(O)N(R3a), C1-6alkyl, —O—C1-6alkyl, —S—C1-6alkyl, and C3-8cycloalkyl,
u is from 0 to ri,
each R3 is independently chosen from the group consisting of hydrogen, C1-6alkyl, —OH, —O—C1-6alkyl and C3-8cycloalkyl, and
each R3a is independently chosen from the group consisting of hydrogen, C1-6alkyl and C3-8cycloalkyl;
is
phenyl, which is substituted by v substituents R2,
each R2 is independently chosen from the group consisting of hydrogen, halogen, —OR4a, —CN, —CO2R4a, —C(O)R4a, —C(O)N(R4a)2, —N(R4a)2, —N(R4a)COR4, —N(R4a)CO2R4a, —N(R4a)C(O)N(R4a), —N(R4a)SO2R4a, —SR4a, —S(O)R4a, —S(O2)R4a, C1-6alkyl substituted by from 0 to 4 R4 and C3-8cycloalkyl substituted by from 0 to 4 R4,
v is from 0 to 4,
each R4 is independently chosen from the group consisting of hydrogen, —OH, C1-6alkyl and C3-8cycloalkyl;
each R4a is independently chosen from the group consisting of hydrogen, C1-6alkyl and C3-8cycloalkyl;
each D is a group independently chosen from
a 5- or 6-membered aryl ring system D′ containing from 0 to 4 heteroatoms independently chosen from the group consisting of N, O and S, and substituted on C or N atoms by from 0 to 2 substituents R5,
each R5 is independently chosen from the group consisting of hydrogen, halogen, —OR6, —CN, —CO2R6, —C(O)N(R6)2, —N(R6)2, —N(R6)COR6, —SR6, —S(O)R6, S(O2)R6, —N(R6)SO2R6, —NCO2R6, —NC(O)N(R6)2, C1-6alkyl substituted by from 0 to 3 R6 and C3-8cycloalkyl substituted by from 0 to 3 R6, and
each R6 is independently chosen from the group consisting of hydrogen, C1-6alkyl and C3-8cycloalkyl;
each E is
a pyrrolidinyl derivative chosen from the group consisting of:
I is a bivalent group chosen from —C(O)—, —CO2— and —C(O)N(R7)—,
J is a fused ring system chosen from the group consisting of 3- to 7-membered carbocycles and 5- or 6-membered aryl rings containing from 0 to 4 heteroatoms independently chosen from the group consisting of N, O and S, and substituted on C or N atoms by substituents R9,
each R8a is independently chosen from the group consisting of hydrogen, halogen, —OH, —OC1-6alkyl and C1-6alkyl, or two R8a may be taken together to form oxo,
each R8b is independently chosen from the group consisting of hydrogen, halogen, —OH, —OC1-6alkyl and C1-6alkyl, or two R8b may be taken together to form oxo,
each R8c is independently chosen from the group consisting of hydrogen and C1-6alkyl,
or any two groups selected from R8a, R8b and R8c may be taken together to form a spiro-bicyclic or bridged bicyclic ring;
each R9 is independently chosen from the group consisting of hydrogen, halogen, C1-6alkyl, —O—C1-6alkyl, —S—C1-6alkyl, —NH—C1-6alkyl and —NHC(O)—C1-6alkyl,
and
each G is independently chosen from the group consisting of:
(a) hydrogen,
(b) —OR10a,
(c) —CN,
(d) —CO2R10a,
(e) —C(O)N(R10)2,
(f) —SR10a,
(g) —S(O)R10a,
(h) —S(O2)R10a,
(i) —N(R10)2,
(j) —N(R10)SO2R10a,
(k) —NCO2R10a,
(l) —NC(O)N(R10)2,
(m) C1-6alkyl having 0 to 4 substituents R11,
each R11 is independently chosen from the group consisting of:
(i) —OH,
(ii) —N(R10)2,
(iii) ═NR10,
(iv) —O—C1-6alkyl,
(v) —C(O)R10,
(vi) —S—C1-6alkyl,
(vii) —SO2—C1-6alkyl,
(viii) 3- to 8-membered carbocycles containing from 0 to 3 heteroatoms independently chosen from the group consisting of N, O and S, and having from 0 to 3 substitutents R12 on N or C atoms, and each R12 is independently selected from the group consisting of hydrogen, halogen, C1-6alkyl having from 0 to 3 substituents chosen from R10, —O—C1-6alkyl, —S—C1-6alkyl, —OR10a, —CN, —C(O)R10, —CO2R10a, —C(O)N(R10)2, —SR10a, —S(O)R10a, —S(O2)R10a, —N(R10)SO2R10a, —NCO2R10a, —NC(O)N(R10)2 and —N(R10)2, or two R12 are taken together to form oxo, and
(ix) 5- or 6-membered aryl containing from 0 to 3 heteroatoms independently chosen from the group consisting of N, O and S, and having from 0 to 3 substitutents R13 on N or C atoms, and each R13 is independently selected from the group consisting of hydrogen, halogen, C1-6alkyl, —O—C1-6alkyl and 3- to 8-membered carbocycles containing from 0 to 3 heteroatoms independently chosen from the group consisting of N, O and S,
(n) 3- to 8-membered carbocycles containing from 0 to 3 heteroatoms independently chosen from the group consisting of N, O and S, and having from 0 to 3 substitutents R10 on N or C atoms;
and
(o) aryl ring systems G′ chosen from the group consisting of:
(i) 5- to 7-membered monocyclic ring systems and
(ii) 8- to 10-membered bicyclic ring systems,
and the aryl ring systems G′ containing from 0 to 4 heteroatoms independently chosen from the group consisting of N, O and S, and substituted on C or N atoms by 0 to 3 substitutents R10;
each R10 is independently chosen from the group consisting of
(i) hydrogen,
(ii) —CN,
(iii) C1-6alkyl,
(iv) —O—C0-6alkyl,
(v) —S—C0-6alkyl,
(vi) C1-6alkyl-O—R14,
(vii) —C(O)R14,
(viii) —CO2R14,
(ix) —SO2R14,
(x) —N(R14)2,
(xi) —N(R14)SO2R14,
(xii) —NCO2R14,
(xiii) —NC(O)N(R14)2, and
(xiv) 3- to 8-membered carbocycles containing from 0 to 3 heteroatoms independently chosen from the group consisting of N, O and S,
or two R10 may be taken together to form oxo;
each R10a is independently chosen from the group consisting of
(i) hydrogen,
(ii) —CN,
(iii) C1-6alkyl,
(iv) C1-6alkyl-O—R14,
(v) —C(O)R14,
(vi) —CO2R14,
(vii) —SO2R14,
(x) —N(R14)2,
(xi) —N(R14)SO2R14,
(xii) —NCO2R14,
(xiii) —NC(O)N(R14)2, and
(xiv) 3- to 8-membered carbocycles containing from 0 to 3 heteroatoms independently chosen from the group consisting of N, O and S,
and two R10 or R10a groups can be taken together with the N to which they are attached to form a ring, which may be substituted by from 0 to 3 substituents R14, and
each R14 is independently chosen from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, —(CH2)0-3C3-8cycloalkyl and phenyl.

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Inhibitors of hepatitis c virus replication

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Inhibitors of hepatitis c virus replication

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Abstract

Claims40