US 2012/0070409 A1 · TETRACYCLIC FUSED HETEROCYCLIC COMPOUND AND USE THEREOF AS HCV POLYMERASE INHIBITOR

Abstract

The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

A compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof:

wherein
is C═C—N or N—C═C,
G3, G4 and G5 are each independently a carbon atom or a nitrogen atom, when at least one of G3, G4 and G5 is a carbon atom, said carbon atom is optionally substituted by R3,
Q is
(1) —(CH2)b— or
(2) —(CH2)c-Q1-(CH2)d—
(wherein b is an integer of 1 to 4,
c and d are each independently 0 or an integer of 1 to 4,
Q1 is
(1′) —O—,
(2′) —NH—,
(3′) —S—,
(4′) —OCO—,
(5′) —OCONH—,
(6′) —CO—,
(7′) —SO—,
(8′) —SO2—,
(9′) —NHCO—,
(10′) —NHSO2—,
(11′) —NHCOO—,
(12′) —COO—,
(13′) —CONH—,
(14′) —SO2NH—,
(15′) —NHCONH—,
(16′) —NHSO2NH—,
(17′) —CH═CH—,
(18′) —CH═N— or
(19′) —N═CH—),
ring A is
(1) benzene,
(2) cyclopentane or cyclohexane,
(3) cyclopentene or cyclohexene or
(4) a 5- or 6-membered heterocycle comprising 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom,
G6 is a carbon atom or a nitrogen atom, a broken line in ring A shows a single bond or a double bond,
R1 is
(1) a carboxyl group,
(2) a carboxylic acid equivalent,
(3) —CONR11R12
(wherein R11 and R12 are each independently
(1′) a hydrogen atom,
(2′) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group E,
(3′) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the following group E,
(4′) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the following group E,
(5′) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
(6′) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group E,
(7′) —NR131R132,
(8′) —NHCOOR133,
(9′) —NHCOR134
(wherein R131, R132, R133 and R134 are each independently a hydrogen atom or a group selected from the following group F),
(10′) —CR135R136-L100-R137,
(11′) —CR135R136-L101-CONR140—R137,
(wherein R135, R136, R138 and R139 are each independently
(1″) a hydrogen atom or
(2″) a group selected from the following group G,
group G:
(1′″) cyano group,
(2′″) —COOR142
(wherein R142 is a hydrogen atom or a group selected from the following group F)
(3′″) —CONR143R144
(wherein R143 and R144 are each independently a hydrogen atom, a C1-6 alkoxy group or a group selected from the following group F)
(4′″) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group A,
(5′″) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the following group A,
(6′″) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the following group B,
(7′″) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
(8′″) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group B,
(9′″) a C6-14 aryl C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the following group B,
(10′″) a heterocycle C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the following group B and
(11′″) a C3-10 cycloalkyl C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the following group B;
or
R135 and R136, or, R138 and R139 are bonded to each other, and optionally form, together with the carbon atom bonded thereto,
(1″) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group B or
(2″) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
R137 is
(1″) a hydrogen atom,
(2″) a carboxyl group,
(3″) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group E,
(4″) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the following group E,
(5″) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the following group E,
(6″) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) or
(7″) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group E,
R140 and R141 are each independently
(1″) a hydrogen atom or
(2″) a C1-6 alkyl group,
L100 is
(1″) a bond,
(2″) —CO—,
(3″) —CH2O—,
(4″) —CH2NH—,
(5″) —CH2NHCO—,
(6″) a C1-6 alkylene optionally substituted by hydroxyl group or
(7″) a C2-6 alkenylene,
L101 and L102 are each independently
(1″) a bond,
(2″) —CO—,
(3″) a C1-6 alkylene optionally substituted by hydroxyl group or
(4″) a C2-6 alkenylene,
L103 is
(1″) a bond or
(2″) a C1-6 alkylene,
L104 is a C1-6 alkylene,
L105 is
(1″) a bond or
(2″) a C1-6 alkylene,
L106 is
(1″) a bond,
(2″) a C1-6 alkylene,
(3″) —NH—,
(4″) —NH—CH2— or
(5″) —CH2—CONH—,
ring D3, ring D4 and ring D5 are each independently
(1″) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the following group E,
(2″) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group E or
(3″) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom))),
(4) —COOR103
(wherein R103 is a group selected from the following group C or a glucuronic acid residue),
(wherein ring D6 is a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
ring D7 is a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the following group E),
R2 may substitute at a substitutable position on carbon atom or nitrogen atom constituting Q and is
(1) a hydrogen atom,
(2) a group selected from the following group E,
(3) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group E,
(4) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the following group E,
{wherein L1 and L2 are each independently
(1′) a bond,
(2′) C1-6 alkylene,
(3′) C2-6 alkenylene,
(4′) —(CH2)u1—O—(CH2)v1—,
(5′) —(CH2)u1—S—(CH2)v1—,
(6′) —(CH2)u1—NRL1—(CH2)v1—,
(7′) —(CH2)u1—CO—(CH2)v1—,
(8′) —(CH2)u1—CONRL2—(CH2)v1—,
(9′) —(CH2)u1—NRL2CO2—(CH2)v1—,
(10′) —(CH2)u1—NRL2CONRL3—(CH2)v1—,
(11′) —(CH2)u1—NRL2CO2—(CH2)v1—,
(12′) —(CH2)u1—NRL2SO2—(CH2)v1—,
(13′) —(CH2)u1—SO2—(CH2)u1—,
(14′) —(CH2)u1—SO2NRL2—(CH2)v1— or
(15′) —(CH2)u1—N+RL2RL2′—(CH2)v1—,
(wherein u, v, u1 and v1 are each independently 0 or an integer of 1 to 6,
RL1 is
(1″) a hydrogen atom,
(2″) a group selected from the following group C,
(3″) —CORL11,
(4″) —CONRL11RL12,
(5″) —COORL11 or
(6″) —SO2RL13
(wherein RL11 and RL12 are each independently a hydrogen atom or a group selected from the following group C, and RL13 is a group selected from the following group C),
RL2, RL2′ and RL3 are each independently
(1″) a hydrogen atom,
(2″) a group selected from the following group C,
(3″) —CORL11 or
(4″) —SO2RL13
(wherein RL11 and RL13 are as defined above)),
L3 is
(1′) —CHRL14— or
(2′) —NRL14—
(wherein RL14 and RL13 are as defined above)),
L3 is
(1′) —CHRL14— or
(2′) —NRL14—
(wherein RL4 is a group selected from the following group F),
ring D1 and ring D2 are each independently
(1′) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the following group E,
(2′) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group E or
(3′) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom)},
R3 is
(1) a hydrogen atom,
(2) a halogen atom,
(3) a C1-6 alkanoyl group,
(4) a carboxyl group,
(5) a cyano group,
(6) a nitro group,
(7) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group A,
(8) —OR101
(wherein R101 is a hydrogen atom or a group selected from the following group C),
(9) —NR102R119
(wherein R102 and R119 are each independently a hydrogen atom, a C1-6 alkanoyl group or a C1-6 alkylsulfonyl group),
(10) —COOR103
(wherein R103 is a group selected from the following group C or a glucuronic acid residue),
(11) —CONR104R105
(wherein R104 and R105 are each independently a hydrogen atom, a hydroxyl group, a cyano group, a C1-6 alkoxy group or a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group A),
(12) —SO2R106
(wherein R106 is a hydroxyl group, an amino group, a C1-6 alkyl group or a C1-6 alkylamino group),
(13) —NHCOR107
(wherein R107 is an amino group or a C1-6 alkylamino group),
(14) —C(═NR108)—NH2
(wherein R108 is a hydrogen atom, a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group A, a hydroxyl group or a C1-6 alkoxy group),
(15) —P(═O)(OR109)2
(wherein R109 are each independently a hydrogen atom or a group selected from the following group C),
(16) —P(═O)(OR110)NR111R112
(wherein R110, R111 and R112 are each independently a hydrogen atom or a group selected from the following group C),
(17) —CONHCO—R113
(wherein R113 is a group selected from the following group C),
(18) —CONHSO2—R114
(wherein R114 is a group selected from the following group C),
(19) —SO2NHCO—R115
(wherein R115 is a group selected from the following group C) or
(20) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
R4 may substitute at a substitutable position on carbon atom or nitrogen atom constituting Q and each is independently
(1) a halogen atom,
(2) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group A,
(3) —OR116
(wherein R116 is a hydrogen atom or a group selected from the following group C),
(4) —NR117R118
(wherein R117 and R118 are each independently a hydrogen atom, a C1-6 alkanoyl group or a group selected from the following group C),
(5) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the following group B or
(6) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
a is 0, 1 or 2,
R5 and R6 are each independently
(1) a hydrogen atom,
(2) a halogen atom,
(3) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the following group A,
(4) —OR120
(wherein R120 is a hydrogen atom or a group selected from the following group C) or
(5) —NR121R122
(wherein R121 and R122 are each independently a hydrogen atom, a C1-6 alkanoyl group or a group selected from the following group C),
ring Cy is
(1) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group B,
(2) a C3-10 cycloalkenyl group optionally substituted by 1 to 5 substituents selected from the following group B or
(3) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
X is
(1) a group selected from the following group D,
(2) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the following group A or
wherein ring B is
(1′) a C6-14 aryl group,
(2′) a C3-10 cycloalkyl group or
(3′) a heterocyclic group comprising 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom,
each Z is independently
(1′) a group selected from the following group D,
(2′) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the following group D,
(3′) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group D,
(4′) a C6-14 aryl C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the following group D,
(5′) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group D
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) or
(6′) a heterocycle C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the following group D
(wherein said heterocycle C1-6 alkyl group is a C1-6 alkyl group substituted by “a heterocyclic group optionally substituted by 1 to 5 substituents selected from group D” as defined above),
w is an integer of 1 to 3,
Y is
(a) C1-6 alkylene,
(b) C2-6 alkenylene or
(c) —Y1—(CH2)m—Y2—(CH2)n—
(wherein m and n are each independently 0 or an integer of 1 to 6,
Y1 and Y2 are each independently
(1′) a bond,
(2′) —O—,
(3′) —NRy1—,
(4′) —S—,
(5′) —CO—,
(6′) —SO—,
(7′) —SO2—,
(8′) —CO2—,
(9′) —OCO—,
(10′) —CONRy2—,
(11′) —NRy2CO—,
(12′) —SO2NRy2—,
(13′) —NRy2SO2—,
(14′) —NRy2CO2—,
(15′) —OCONRy2—,
(16′) —NRy2CONRy3—,
(17′) —CRy2Ry5— or
(18′) —CH═CH—
(wherein Ry1 is
(1″) a hydrogen atom,
(2″) a group selected from the following group C,
(3″) —(CH2)s—COORy11,
(4″) —(CH2)s—CONRy11Ry12,
(5″) (CH2)s—CORy11 or
(6″) —(CH2)s—SO2Ry13
(wherein s is 0 or an integer of 1 to 6, Ry11 and Ry12 are each independently a hydrogen atom or a group selected from the following group C, Ry13 is a group selected from the following group C),
Ry2 and Ry3 are each independently
(1″) a hydrogen atom,
(2″) a group selected from the following group C,
(3″) —CORy11 or
(4″) —SO2Ry13 (wherein Ry11 and Ry13 are as defined above),
Ry4 and Ry5 are each independently
(1″) a hydrogen atom,
(2″) a carboxyl group,
(3″) a group selected from group F,
(4″) —ORy14 or
(5″) —NHRy15
(wherein Ry14 is a group selected from the following group C, Ry15 is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkanoyl group, a C6-14 aryl C1-6 alkyloxycarbonyl group or a C1-6 alkoxycarbonyl group)))
group A:
(1) a halogen atom,
(2) a C1-6 alkoxy C1-6 alkoxy group,
(3) a cyano group,
(4) —ORa1,
(5) —SRa1,
(6) —NRa1Ra2,
(7) —COORa1,
(8) —CONRa1Ra2,
(9) —SO3H,
(10) —SO2NRa1Ra2,
(11) —NHCORa1,
(12) —NHSO2Ra3,
(13) —NHCO2Ra4,
(14) —CORa1 and
(15) —N+Ra1Ra2Ra3
(wherein Ra1 and Ra2 are each a hydrogen atom, a C1-6 alkyl group or a benzyl group, Ra3 is a C1-6 alkyl group and Ra4 is a C1-6 alkyl group)
group B:
(1) a halogen atom,
(2) a cyano group,
(3) a nitro group,
(4) a C1-6 alkyl group,
(5) a C2-6 alkenyl group optionally substituted by carboxyl group,
(6) a halogenated C1-6 alkyl group,
(7) —(CH2)r—ORb1,
(8) —(CH2)r—SRb1,
(9) —(CH2)r—NRb1Rb2,
(10) —(CH2)r—COORb1,
(11) —(CH2)r—CONRb1Rb2,
(12) —(CH2)r—CORb1,
(13) —(CH2)r—NRb1—CORb2,
(14) —(CH2)r—NRb1—SO2Rb3,
(15) —(CH2)r—SO2Rb3,
(16) —(CH2)r—SO2NRb1Rb2,
(17) —(CH2)r—CONRb1—SO2Rb3,
(18) —(CH2)r—SO2NRb1—CORb2,
(19) —(CH2)r—NRb1—COORb3,
(20) —(CH2)r—NRb1—CONRb2Rb4,
(21) —O—(CH2)r—COORb1 and
(22) —CO—(CH2)r—Rb5
(wherein Rb1, Rb2 and Rb4 are each independently a hydrogen atom or a C1-6 alkyl group, Rb3 is a C1-6 alkyl group, Rb5 is a heterocyclic group and r is 0 or an integer of 1 to 6)
(1) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
(2) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
(3) a C6-14 aryl C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
(4) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B and
(5) a heterocycle C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
group D:
(a) a hydrogen atom,
(b) a halogen atom,
(c) a cyano group,
(d) a nitro group,
(e) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
(f) —(CH2)t—ORd1,
wherein Rd1 is
(1) a hydrogen atom,
(2) a group selected from the following group F,
(3) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or
(4) a C2-6 alkynyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
hereinafter each t is independently 0 or an integer of 1 to 6,
(g) —(CH2)t—S(O)q—Rd2,
wherein Rd2 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
q is 0, 1, 2 or 3,
(h) —(CH2)t—NRd3Rd4,
wherein Rd3 and Rd4 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(i) —(CH2)t—COORd5,
wherein Rd5 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
(j) —(CH2)t—CONRd6Rd7,
wherein Rd6 and Rd7 are each independently
(1) a hydrogen atom,
(2) a hydroxyl group,
(3) a group selected from the following group F or
(4) a C1-6 alkoxy group,
(k) —(CH2)t—CORd8,
wherein Rd8 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
(l) —(CH2)t—NRd9CO—Rd10,
wherein Rd9 is
(1) a hydrogen atom,
(2) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or
(3) a C1-6 alkanoyl group,
Rd10 is
(1) an amino group,
(2) a C1-6 alkylamino group or
(3) a group selected from the following group F,
(m) —(CH2)t—NRd11SO2—Rd12,
wherein Rd11 is
(1) a hydrogen atom,
(2) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or
(3) a C1-6 alkanoyl group,
Rd12 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
(n) —(CH2)t—SO2—NRd13Rd14,
wherein Rd13 and Rd14 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(o) —(CH2)t—CONRd15—SO2Rd16,
wherein Rd15 and Rd16 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(p) —(CH2)t—SO2NRd17—CORd18,
wherein Rd17 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
Rd18 is a group selected from the following group F,
(q) —(CH2)t—NRd19—COORd20,
wherein Rd19 and Rd20 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(r) —(CH2)t—NRd21—CONRd22Rd23,
wherein Rd21, Rd22 and Rd23 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(s) —(CH2)t—C(═NRd24)NH2,
wherein Rd24 is
(1) a hydrogen atom,
(2) a hydroxyl group,
(3) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or
(4) C1-6 alkoxy group,
(t) —(CH2)t—O—(CH2)p—CORd25,
wherein Rd25 is
(1) an amino group,
(2) a C1-6 alkylamino group or
(3) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
p is 0 or an integer of 1 to 6,
(u) —(CH2)t—O—(CH2)p—NRd26Rd27,
wherein Rd26 and Rd27 are each independently
(1) a hydrogen atom or
(2) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
p is 0 or an integer of 1 to 6,
(v) —(CH2)t—O—COORd28,
wherein Rd28 is
(1) a hydrogen atom or
(2) a group selected from the following group F, and
(w) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom)
group E:
(a) a halogen atom,
(b) a cyano group,
(c) a nitro group,
(d) an azido group,
(e) —OP(═O)(OH)2,
(f) —ORe1,
wherein Re1 is
(1) a hydrogen atom,
(2) a group selected from the following group F,
(3) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or
(4) a C2-6 alkynyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
(g) —S(O)q—Re2
wherein Re2 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
q is 0, 1, 2 or 3,
(h) —NRe3Re4,
wherein Re3 and Re4 are each independently
(1) a hydrogen atom,
(2) a cyano group or
(3) a group selected from the following group F,
(i) —COORe5,
wherein Re5 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
(j) —CONRe6Re7,
wherein Re6 and Re7 are each independently
(1) a hydrogen atom,
(2) a hydroxyl group,
(3) a group selected from the following group F or
(4) a C1-6 alkoxy group,
(k) —CORe8,
wherein Re8 is a group selected from the following group F,
(l) —NRe9CO—Re10,
wherein Re9 is
(1) a hydrogen atom,
(2) a C1-6 alkyl group or
(3) a C1-6 alkanoyl group,
Re10 is
(1) a hydrogen atom,
(2) an amino group,
(3) a C1-6 alkylamino group,
(4) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or
(5) a group selected from the following group F,
(m) —NRe11SO2—Re12,
wherein Re11 is
(1) a hydrogen atom,
(2) a C1-6 alkyl group or
(3) a C1-6 alkanoyl group,
Re12 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
(n) —SO2—NRe13Re14,
wherein Re13 and Re14 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(o) —CONRe15—SO2Re16,
wherein Re15 and Re16 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(p) —SO2NRe17—CORe18,
wherein Re17 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
Re18 is a group selected from the following group F,
(q) —NRe19—COORe20,
wherein Re19 and Re20 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(r) —NRe21—CONRe22Re23
wherein Re21, Re22 and Re23 are each independently
(1) a hydrogen atom or
(2) a group selected from the following group F,
(s) —NHCO—COORe24
wherein Re24 is
(1) a hydrogen atom or
(2) a group selected from the following group F,
(t) —NHCO—CONRe25
wherein Re25 and Re26 are each independently
(1) a hydrogen atom,
(2) a hydroxyl group or
(3) a group selected from the following group F,
(u) —CONH—COOH,
(y) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
(z) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
(aa) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
(bb) a C3-10 cycloalkylidene group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, and
(cc) a heterocycle ylidene group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
(wherein said heterocycle ylidene group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
when group E is a substituent on a C6-14 aryl group, a C3-10 cycloalkyl group or a heterocyclic group, it may be
(dd) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
(ee) a C2-6 alkenyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
(ff) a C2-6 alkynyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
(gg) C1-6 alkylidene group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
(hh) a C6-14 aryl C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
(ii) a C3-10 cycloalkyl C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, or
(jj) a heterocycle C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
group F:
(1) a C1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A,
(2) a C6-14 aryl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
(3) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
(wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
(4) a C3-10 cycloalkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
(5) a C6-14 aryl C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B,
(6) a heterocycle C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
(wherein said heterocycle C1-6 alkyl group is a C1-6 alkyl group substituted by “a heterocyclic group optionally substituted by 1 to 5 substituents selected from group B” as defined above) and
(7) a C3-10 cycloalkyl C1-6 alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B.

540 more elements

Tetracyclic fused heterocyclic compound and use thereof as hcv polymerase inhibitor

Life of this patent

Tetracyclic fused heterocyclic compound and use thereof as hcv polymerase inhibitor

Life of this patent

Abstract

Claims14