Heterocyclic antiviral compounds

1. A compound according to formula I:

A-R  (I)

wherein:

A is 2 oxo-1,2-dihydro-pyridin-3-yl;

R is Ia, Ib or Ic;

X is NR 4 or O;

X 1 and X 2 together are oxo;

R 3a is hydrogen and R 3b is CH 2 Ar or R 3a and R 3b together are ═CHAr;

Ar is phenyl optionally independently substituted with one to three substitutents selected from the group consisting of (a) hydroxy, (b) C 1-6 alkoxy, (c) C 1-6 alkyl, (d) C 1-6 hydroxyalkyl, (f) halogen, (h) cyano, (i) CO 2 R 5 , (j) CONR c R d , (k) C 1-3 acylamino, (l) (CH 2 ) n NR a R b , (m) (CH 2 ) n CONR c R d , (n) (CH 2 ) n SO 2 NR c R d , (o) (CH 2 ) n SO 2 R 5 and (p) O(CH 2 ) n CONR c R d ;

R a and R b are independently in each occurrence (a) hydrogen, (b) C 1-6 alkyl, (c) C 1-6 acyl, (d) C 1-6 alkylsulfonyl, (e) C 1-6 haloalkylsulfonyl, (f) C 3-7 cycloalkylsulfonyl, (g) C 3-7 cycloalkyl-C 1-3 alkyl-sulfonyl or (h) C 1-6 alkoxy-C 1-6 alkylsulfonyl, (i) SO 2 (CH 2 ) n NR c R d , (j) carbamoyl, (k) C 1-3 alkylcarbamoyl, (l) C 1-3 dialkylcarbamoyl or (m) benzoyl said benzoyl optionally independently substituted with one or two groups selected from the group consisting of amino, halogen, C 1-6 alkyl or C 1-3 alkylsulfonylamino;

R c and R d are independently in each occurrence hydrogen, C 1-6 alkyl, C 1-6 acyl, or together with the nitrogen to which they are attached form a cyclic amine;

R 1 is hydrogen, C 1-6 alkyloxy or C 1-6 haloalkyloxy or R 1 and R 2a together are CH 2 —O and together with atoms to which they are attached form a 2,3-dihydrobenzofuran;

R 6 is hydrogen;

R 4 is hydrogen or C 1-6 alkyl;

R 5 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-3 alkoxy-C 1-3 alkyl or optionally substituted benzyl;

R 2a , R 2b and R 2c each are independently C 1-3 alkyl;

n is independently in each occurrence an integer from zero to three; or,

a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein R is Ia and R 2a , R 2b and R 2c each are methyl.

3. The compound according to claim 2 wherein Ar is phenyl substituted at least by (CH 2 ) n NR a R b wherein R a is C 1-6 acyl, C 1-6 alkylsulfonyl, C 1-6 haloalkylsulfonyl, C 3-7 cycloalkylsulfonyl, C 3-7 cycloalkyl-C 1-3 alkyl-sulfonyl or C 1-6 alkoxy-C 1-6 alkylsulfonyl, R b is hydrogen and n is zero.

4. The compound according to claim 3 wherein R a is C 1-6 alkylsulfonyl.

5. The compound according to claim 1 wherein R is Ib.

6. The compound according to claim 5 wherein R 2a , R 2b and R 2c each are methyl.

7. The compound according to claim 6 wherein Ar is phenyl substituted at least by (CH 2 ) n NR a R b , R a is C 1-6 acyl, C 1-6 alkylsulfonyl, C 1-6 haloalkylsulfonyl, C 3-7 cycloalkylsulfonyl, C 3-7 cycloalkyl-C 1-3 alkyl-sulfonyl or C 1-6 alkoxy-C 1-6 alkylsulfonyl, R b is hydrogen and n is zero.

8. The compound according to claim 1 wherein R is Ic.

9. The compound according to claim 8 wherein R 3a is hydrogen and R 3b is CH 2 Ar, Ar is optionally substituted phenyl and R 2a , R 2b and R 2c each are methyl.

10. The compound according to claim 9 wherein Ar is phenyl substituted at least by (CH 2 ) n NR a R b , R a is C 1-6 acyl, C 1-6 alkylsulfonyl, C 1-6 haloalkylsulfonyl, C 3-7 cycloalkylsulfonyl, C 3-7 cycloalkyl-C 1-3 alkyl-sulfonyl or C 1-6 alkoxy-C 1-6 alkylsulfonyl, R b is hydrogen and n is zero.

11. The compound according to claim 8 wherein R 3a and R 3b together are ═CHAr, Ar is optionally substituted phenyl and R 2a , R 2b and R 2c are methyl.

12. The compound according to claim 11 wherein Ar is phenyl substituted at least by (CH 2 ) n NR a R b , R a is C 1-6 acyl, C 1-6 alkylsulfonyl, C 1-6 haloalkylsulfonyl, C 3-7 cycloalkylsulfonyl, C 3-7 cycloalkyl-C 1-3 alkyl-sulfonyl or C 1-6 alkoxy-C 1-6 alkylsulfonyl, R b is hydrogen and n is zero.

13. The compound according to claim 1 selected from the group consisting of:

3-[3-(4-amino-phenyl)-6-tert-butyl-2-oxo-2H-chromen-8-yl]-1H-pyridin-2-one;

6-tert-butyl-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-3-phenyl-1H-quinolin-2-one;

N-{-4-[6-tert-butyl-2-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-2H-chromen-3-yl]-phenyl}-methanesulfonamide;

6-tert-butyl-1-methyl-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-3-phenyl-1H-quinolin-2-one;

6-tert-butyl-3-(4-hydroxy-phenyl)-1-methyl-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1H-quinolin-2-one;

N-{4-[6-tert-butyl-1-methyl-2-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1,2-dihydro-quinolin-3-yl]-phenyl}-methanesulfonamide;

N-{4-[6-tert-butyl-2-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1,2-dihydro-quinolin-3-yl]-phenyl}-methanesulfonamide;

N-{3-[6-tert-butyl-2-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1,2-dihydro-quinolin-3-yl]-phenyl}-methanesulfonamide;

4-[6-tert-butyl-2-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1,2-dihydro-quinolin-3-yl]-benzenesulfonamide;

4-[6-tert-butyl-1-methyl-2-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1,2-dihydro-quinolin-3-yl]-benzenesulfonamide;

3-[6-tert-butyl-2-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1,2-dihydro-quinolin-3-yl]-benzamide;

N-{4-[6-tert-butyl-1-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1,2-dihydro-isoquinolin-3-yl]-phenyl}-methanesulfonamide;

N-{-4-[6-tert-butyl-1-oxo-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-1H-isochromen-3-yl]-phenyl}-methane sulfonamide;

N-{-4-[6-tert-Butyl-2-hydroxy-8-(2-oxo-1,2-dihydro-pyridin-3-yl)-chroman-3-yl]-phenyl}-methanesulfonamide;

N-{4-[6-tert-Butyl-3-oxo-4-(2-oxo-1,2-dihydro-pyridin-3-yl)-3H-isobenzofuran-(1Z)-ylidenemethyl]-phenyl}-methanesulfonamide; and,

N-{-4-[6-tert-Butyl-3-oxo-4-(2-oxo-1,2-dihydro-pyridin-3-yl)-1,3-dihydro-isobenzofuran-1-ylmethyl]-phenyl}-methanesulfonamide; or,

a pharmaceutically acceptable salt thereof.

14. A composition comprising a compound according to claim 1 admixed with at least one pharmaceutically acceptable carrier, diluent or excipient.