Heterocyclic antiviral compounds

A compound according to formula I

• wherein:
• R1 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, halogen, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, cyano, NRaRb, carboxy, C1-3 alkoxycarbonyl, carboxamido, amino C1-3alkyl, C1-3 acylamino C1-3alkyl, C1-6 hydroxyalkoxy,
• R2 is selected from the group consisting of:
• (a) —[C(R8)2]p—Ar1 (b) —[C(R8)2]p—OAr1, (c) —(CH2)nC(═O)X, (d) —NR7C(═O)Ar4, (e) —C1-6 alkyl, (f) —C1-6 haloalkyl, (g) C1-6 alkoxy, (h) C1-6haloalkoxy, (i) C1-6 hydroxyalkyl, (j) hydroxy, (k) halogen, (l) hydrogen, (m) phenylsulfonyl, (n) —O(CH2)mAr1, (o) —[C(R8)2]1, —NReRf, (p) (E)- or (Z)-R10C═CR10Ar1—, and (q) —C≡CAr1 wherein R8 is independently in each occurrence hydrogen, carboxyl, C1-3 alkoxycarbonyl, carboxamido, C1-3 hydroxyalkyl, C1-3 alkyl, —(CH2)rNRgRh or cyano, R10 is independently in each occurrence hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, cyano, alkoxycarbonyl, carboxamido, carboxyl or C1-3alkoxy-C1-6alkyl, p is zero to four and r is 1 to 3;
• Ar1 is phenyl optionally independently substituted with one to three substitutents selected from the group consisting of (a) hydroxy, (b) C1-6 alkoxy, (c) C1-6 alkyl, (d) C1-10 hydroxyalkyl wherein one or two carbon atoms optionally can be replaced by oxygen provided the replacement does not form a oxygen-oxygen bond, (e) C1-3 alkoxy-C1-6 alkyl, (f) halogen, (g) cyano, (h) C1-6 alkoxycarbonyl, (i) C1-6 alkylsulfonyl, (j) X1(CH2)1-6CO2H, (k) C1-3 acylamino-C1-6 alkyl, (l) (CH2)nNRaRb, (m) (CH2)nCONRaRb, (n) —O(CH2)nCONRaRb, (o) X2(CH2)2-6NRgRh, (p) X1—C1-6 hydroxyalkyl, (q) C1-6 haloalkyl, and (r) carboxyl;
• Ra and Rb are (i) independently in each occurrence (a) hydrogen, (b) C1-6 alkyl, (c) C1-3 haloalkyl, (d) C1-6 acyl, (e) C1-6 alkylsulfonyl, (f) C1-6 haloalkylsulfonyl, (g) C3-7 cycloalkylsulfonyl, (h) C3-7 cycloalkyl-C1-3 alkyl-sulfonyl, (i) C1-6 alkoxy-C1-6 alkylsulfonyl, (i) (CH2)1-3NRgRh, (k) SO2(CH2)1-6NRgRh wherein R9 and R10 are as defined above, (l) sulfamoyl (m) C1-3 alkylsulfamoyl, (n) C1-3 dialkylsulfamoyl, (o) carbamoyl, (p) C1-3 alkylcarbamoyl, (q) C1-3 dialkylcarbamoyl, (r) benzoyl said benzoyl optionally independently substituted with one or two groups selected from the group consisting of amino, halogen, C1-6 alkyl or C1-3 alkylsulfonylamido, (r) C1-6 carboxyalkylsulfonyl, (s) C2-6 hydroxyalkylsulfonyl;
• Re and Rf when (i) taken independently are selected from (a) hydrogen, (b) C1-3 alkyl, (c) C4-7 cycloalkyl (d) C3-7 cycloalkylcarbonyl or (e) phenyl said cycloalkyl and said phenyl are optionally independently substituted with one to three groups selected from C1-3 alkylsulfonylamido, C1-3 alkyl, C1-3 alkoxy or halogen;
• X is OH, C1-6 alkoxy, NReRd or Ar3;
• Ar3 is phenyl optionally substituted with one to three substitutents selected from the group consisting of:
• (a) halogen, (b) hydroxy, (c) C1-3 hydroxyalkyl, (d) amino, (e) amino-C1-3 alkyl, (f) C1-3 alkylamino (g) C1-3 alkylamino-C1-3 alkyl, (h) C1-3 dialkylamino, (i) C1-3 dialkylamino-C1-3 alkyl, (j) carboxamido, (k) C1-6 alkylsulfonylamido, (l) C1-6 alkylsulfonylamido-C1-3 alkyl, (m) NR7—C1-3 alkyl-C1-6 alkylsulfonamido, (n) C1-6 alkyl, (o)C1-6 alkoxycarbonyl and (p) carboxyl;
• Re and Rd are (i) independently in each occurrence:
• (a) hydrogen, (b) Ar2, (c) Ar2—C1-6 alkyl, (d) C3-6 cycloalkyl optionally substituted C1-3 dialkylamino, C1-6 alkylsulfonamido or C1-3 hydroxyalkyl, (e) C1-6 alkyl-C3-7 cycloalkyl, (f) alkoxy-C1-3 alkyl;
• Ar2 is phenyl optionally substituted with one to three substituents independently selected from the group consisting of (a) C1-3 alkyl (b) amino, (c) amino C1-3 alkyl, (d) C1-3 alkylamino, (e) C1-3 alkylamino-C1-3 alkyl, (f) C1-3 dialkylamino, (g) —OCH2CO NRgRh (h) C1-3 alkylsulfonylamido, (i) C1-3 alkylsulfonamido-C1-3 alkyl, (j) N—C1-3 alkyl-C1-6 alkylsulfonamido, (k) C1-3 hydroxyalkyl, and (l) hydroxy;
• Ar4 is phenyl optionally substituted with one to three substituents independently selected in each occurrence from the group consisting of (a) amino, (b) C1-3 alkylamino, (c) di-C1-3 alkylamino, (d) C1-3 haloalkylamino, (e) C1-6 alkylsulfonylamido, (f) sulfamoyl, (g) C1-3 alkylsulfamoyl, (h) C1-3 dialkylsulfamoyl, (i) C1-6 alkylsulfonylamido-C1-3 alkyl, (j) NR7—C1-3 alkyl-C1-6 alkylsulfonamido, (k) halogen, (l) C1-3 alkyl, (m) C1-3 alkoxy, (n) C1-6 acylamino, (o) hydroxy, (CH2)6CONRaRb, (q) —O(CH2)nCONRaRb, (r) —O(CH2)nNRiRj, (s) —NRi(CH2)nORj, (t) C1-3-haloalkyl, (u) C1-3 alkoxy-C1-6 alkoxy, (v) C3-6 cycloalkylamine wherein Ri and Rj are independently hydrogen or C1-3 alkyl;
• R7 is independently in each occurrence hydrogen or C1-3 alkyl;
• R3 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-3 alkoxy-C1-6 alkoxy, halogen, O(CH2)2-6X3 wherein X3 is OH or N(R7)2 or R3 and R4a together are (CH2)2 and with atoms to which they are attached form an indane;
• R4a, R4b and R4c (a) when taken independently are each selected independently from (i) C1-3 alkyl, (ii) C1-2 alkoxy, (iii) C1-2 fluoroalkyl, (iv) C3 hydroxyalkyl, (v) hydroxy (vi) CO2H, (vii) C1-6 alkoxycarbonyl, (viii) cyano or (ix) N(R7)2 or (b) when taken together, (i) R4a and R4b together are C2-4 methylene and R4c is hydrogen, C1-3 alkyl, C1-2 alkoxy, halogen, cyano or C1-2 fluoroalkyl or (c) either (i) R5 and R4a or (ii) R3 and R4a together are (CH2)2 and with atoms to which they are attached form an indane and R4b and R4c are C1-3 alkyl or (d) R4a, R4b, R4c together with the carbon to which they are attached are cyclopropyl, trifluoromethyl or 2,2,2-trifluoroethyl;
• R5 is hydrogen, halogen, C1-6 alkyl, hydroxy or R5 and R4a together are (CH2)2 and together with atoms to which they are attached form an indane;
• R6 is (a) halogen, (b) C1-6 alkyl wherein one or two non-adjacent carbon atoms optionally can be replaced by oxygen, (c) C1-3 haloalkyl, (d) C1-3 alkoxy, (e) X1—C2-6 hydroxyalkyl wherein one or two non-adjacent carbon atoms optionally can be replaced by oxygen, (f) cyano-C1-3 alkyl, (g) X1(CH2)1-6CO2H or (h) X1—(CH2)2-6NRgRh;
• R9 is hydrogen, CH2OH, CH2OR9a, CH(Me)OH, CH(Me)OR9a wherein R9a is (a) CO(CH2)sCO2H wherein s is one to four, (b) C(O)CHR9bNHR9c wherein R9b is hydrogen, methyl, iso-propyl, iso-butyl, sec-butyl, phenyl or 4-hydroxy-phenyl and R9c is hydrogen or C1-6 alkoxycarbonyl or R9b and R9c together are (CH2)3, (c) —P(O)(OH)2 or (d) COR11 wherein R11 is C1-6 alkyl or optionally substituted aryl;
• X1 is O, NR7, or a bond;
• X2 is O or NR7;
• Rg and Rh are independently hydrogen or C1-6 alkyl;
• m is zero to three;
• n is independently in each occurrence zero to two;
• or,
• pharmaceutically acceptable salts thereof.