Indole acetamides as inhibitors of the hepatitis c virus ns5b polymerase

A compound of formula (I):

• wherein
• Ar1 is a moiety containing at least one aromatic ring and possesses 5-, 6-, 9- or 10-ring atoms optionally containing 1, 2 or 3 heteroatoms independently selected from N, O and S, which ring is optionally substituted at any substitutable position by groups Q1 and Q2;
• Q1 is halogen, hydroxy, C1-4 alkyl, C1-4 alkoxy, aryl, heteroaryl, CONRcRd, CmH2mNRcRd, —O—(CH2)2-4NRcRd, —O—CmH2mCONRcRd, —O—CmH2m aryl, —O—CmH2m heteroaryl, —O—CHReRf;
• Rc and Rd are each independently selected from hydrogen, C1-4 alkyl and C(O)C1-4 alkyl;
• or Rc, Rd and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, where said ring is optionally substituted by halogen, hydroxy, C1-4 alkyl or C1-4 alkoxy;
• m is 0, 1, 2 or 3
• Re and Rf are each independently selected from hydrogen and C1-4 alkoxy;
• or Re and Rf are linked by a heteroatom selected from N, O and S to form a heteroaliphatic ring of 4 to 7 ring atoms, where said ring is optionally substituted by halogen, hydroxy, C1-4 alkyl or C1-4alkoxy;
• and wherein said C1-4 alkyl, C1-4 alkoxy and aryl groups are optionally substituted by halogen or hydroxy;
• Q2 is halogen, hydroxy, C1-4 alkyl or C1-4 alkoxy, where said C1-4 alkyl and C1-4 alkoxy groups are optionally substituted by halogen or hydroxyl;
• or Q1 and Q2 may be linked by a bond or a heteroatom selected from N, O and S to form a ring of 4 to 7 atoms, where said ring is optionally substituted by halogen, hydroxy, C1-4 alkyl or C1-4 alkoxy;
• A1 is C1-6 alkyl, C2-6 alkenyl, where said C1-6 alkyl and C2-6 alkenyl groups are optionally substituted by C1-4 alkoxy or up to 5 fluorine atoms, or a non-aromatic ring of 3 to 8 ring atoms where said ring may contain a double bond and/or may contain a O, S, SO, SO2 or NH moiety and where said ring is optionally substituted by one or two alkyl groups of up to 2 carbon atoms or by 1 to 8 fluorine atoms, or a non-aromatic bicyclic moiety of 4 to 8 ring atoms which ring may be optionally substituted by fluorine or hydroxy;
• X1 is N or CRa;
• X2 is N or CR3;
• X3 is N or CR4;
• X4 is N or CRb;
• with the proviso that X2 and X3 are not both N;
• Ra and Rb are each independently selected from hydrogen, fluorine, chlorine, C1-4 alkyl, C2-4 alkenyl or C1-4 alkoxy, where said C1-4 alkyl, C2-4 alkenyl and C1-4 alkoxy groups ar optionally substituted by hydroxy or fluorine;
• one of R3 or R4is hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy, CN, CO2H, CO2C1-4 alkyl, aryl, heteroaryl or C(O)NR9R10, where said C1-4 alkyl, C1-4 alkoxy, aryl and heteroaryl groups are optionally substituted by hydroxy or fluorine;
• R9 is hydrogen or C1-4 alkyl;
• R10 is hydrogen, C1-4 alkyl, C2-4 alkenyl or (CH2)0-3R12 or SO2R11;
• R12 is NRhRi, ORh, aryl, heteroaryl, indolyl or Het;
• Rh and Ri are each independently selected from hydrogen and C1-4 alkyl;
• Het is a heteroaliphatic ring of 4 to 7 ring atoms, which ring may contain 1, 2 or 3 heteroatoms selected from N, O or S or a group S(O), S(O)2, NH or NC1-4 alkyl;
• R11 is C1-4 alkyl, C2-4 alkenyl or (CH2)0-3R13;
• R13 is aryl, heteroaryl, C1-4 alkyl, C3-8 cycloalkyl, Het or NRmRn, wherein Het is as hereinbefore defined, Rm and Rn are each independently selected from hydrogen, C1-4 alkyl and CO2(CH2)0-3aryl, and wherein R13 is optionally substituted by halogen, C1-4 alkyl or NRoRp, wherein Ro and Rp are each independently selected from hydrogen and C1-4 alkyl;
• and where R10 is optionally substituted by hydroxy, fluorine, chlorine, C1-4 alkyl, ═O, CO2H or CO2C1-4 alkyl;
• or R9,R10 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, where said ring is optionally substituted by halogen, hydroxy, ═O, C1-4 alkyl or C1-4 alkoxy;
• the other of R3 and R4is hydrogen, fluorine, chlorine, C1-4 alkyl, C2-4 alkenyl or C1-4 alkoxy, where said C1-4 alkyl, C2-4 alkenyl and C1-4 alkoxy groups are optionally substituted by hydroxy or fluorine;
• n is 1, 2, 3 or 4;
• R1 and R2 are each independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C1-6 alkynyl, C1-4 alkoxy, C3-8 cycloalkyl C1-4 alkyl, (CH2)0-3R14;
• R14 is aryl, heteroaryl, NRqRr, Het, where Het is as hereinbefore defined;
• Rq and Rr are each independently selected from hydrogen and C1-4 alkyl;
• or Rq, Rr and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms;
• and R1 and R2 are optionally substituted by hydroxy, C1-4 alkyl, ═O, C(O)C1-4 alkyl or C3-8 cycloalkyl;
• or R1, R2 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring optionally contains 1, 2 or 3 additional heteroatoms selected from O and S or a group S(O), S(O)2, NH or NRs, where Rs is C1-4 alkyl or heteroaryl, or said heteroaliphatic ring is fused to or substituted by a spiro-fused five- or six-membered nitrogen-containing heteroaliphatic ring, which heteroaliphatic ring is optionally substituted by hydroxy, C1-4 alkyl, C1-4 alkoxy, (CH2)0-3NRtRu, aryl, heteroaryl, or a —CH2— or —CH2CH2— alkylene bridge, where aryl and heteroaryl are optionally substituted by hydroxy, C1-4 alkyl or C1-4 alkoxy;
• Rt and Ru are each independently selected from hydrogen, C1-4 alkyl and C(O)C1-4 alkyl,
• or Rt, Ru and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms optionally substituted by C1-4 alkyl;
• or a pharmaceutically acceptable salt thereof.