Tetracyclic xanthene derivatives and methods of use thereof for the treatment of viral diseases

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof,

wherein:

A is N or CH;

each of Y 1 and Y 2 is independently —[C(R 1 ) 2 ] w — or —Si(R b ) 2 ;

Z is —C(R a )═C(R a )—, —[C(R a ) 3 ] t —, —O—C(R a )═, —N(R a )—C(R a )═, —C(R a )═N—, —O—[C(R a ) 2 ] w — or —N(R a )—C(R a ) 2 —C(R a ) 2 —, such that when Z is —O—C(R a )═ or —N(R a )—C(R a )═, then A is carbon;

each occurrence of R a is independently H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, 4- to 7-membered heterocycloalkyl or 5- to 6-membered heteroaryl;

each occurrence of R b is independently C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, 4- to 7-membered heterocycloalkyl or 5- to 6-membered heteroaryl;

each occurrence of R 1 is independently H, C 1 -C 6 alkyl, halo, C 1 -C 6 haloalkyl,

—O—C 1 -C 6 alkyl or —CN, or two R 1 groups that are attached to the same carbon atom, together with the common carbon atom to which they are attached, can join to form a spirocyclic C 3 -C 6 cycloalkyl group or a spirocyclic 4- to 7-membered heterocycloalkyl group;

each occurrence of R 1a is independently H, C 1 -C 6 alkyl, CN, halo, C 1 -C 6 haloalkyl, —OH, —O—(C 1 -C 6 alkyl), —O—(C 1 -C 6 haloalkyl), or two R 1a groups, together with the carbon atoms to which they are attached, join to form a C 3 -C 6 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, or when Y 1 is carbon, one R 1a group and Y 1 , together with the carbon atoms to which they are attached, join to form a C 3 -C 6 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group;

each occurrence of R 1b is independently H, C 1 -C 6 alkyl, CN, halo, C 1 -C 6 haloalkyl, —OH, —O—(C 1 -C 6 alkyl), —O—(C 1 -C 6 haloalkyl), or two R 1b groups, together with the carbon atoms to which they are attached, join to form a C 3 -C 6 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, or when Y 2 is carbon, one R 1b group and Y 2 , together with the carbon atoms to which they are attached, join to form a C 3 -C 6 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group;

each occurrence of R 2 is independently H, halo, or alkyl;

t is 1, 2 or 3; and

each occurrence of w is independently 1 or 2.

2. The compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof,

wherein:

A is N or CH;

each of Y 1 and Y 2 is independently —CH 2 —, —CF 2 — or —CHF—;

Z is —OCH 2 —, —OCH 2 CH 2 —, —O—CH═, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH═CH— or —CH═N—, such that when Z is —O—CH═, then A is carbon;

each occurrence of R a is independently C 1 -C 6 alkyl, C 6 -C 10 aryl or C 3 -C 7 cycloalkyl; and

each occurrence of R b is independently C 1 -C 6 alkyl.

3. The compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof,

wherein:

A is N or CH;

each of Y 1 and Y 2 is independently —CH 2 —, —CF 2 — or —CHF—;

Z is —OCH 2 —, —OCH 2 CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH═CH— or —CH═N such that when Z is —O—CH═, then A is carbon;

each occurrence of R a is independently C 1 -C 6 alkyl, C 6 -C 10 aryl or C 3 -C 7 cycloalkyl; and

each occurrence of R b is independently C 1 -C 6 alkyl.

4. The compound of claim 1 , wherein A is N and Z is —CH═CH—, —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 —.

5. The compound of claim 4 , wherein Y 1 and Y 2 are each independently selected from —CH 2 —, —CF z — and —CHF—.

6. The compound of claim 5 , wherein each occurrence of R a is C 1 -C 6 alkyl or C 3 -C 7 cycloalkyl; and each occurrence of R b is C 1 -C 6 alkyl.

7. The compound of claim 6 , wherein each occurrence of R a is independently isopropyl, t-butyl or cyclopropyl.

8. The compound of claim 7 , wherein each occurrence of R a is isopropyl.

9. The compound of claim 8 , wherein each occurrence of R b is methyl.

10. The compound of claim 9 , wherein each occurrence of R 1a , R 1b and R 2 is H.

11. The compound of claim 1 having the structure:

or a pharmaceutically acceptable salt thereof.

12. A method of treating a patient infected with HCV comprising the step of administering an amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, effective to treat infection by HCV in said patient.

13. The method according to claim 12 , further comprising the step of administering an HCV protease inhibitor to said patient.

14. The method according to claim 12 , further comprising the step of administering an HCV polymerase inhibitor to said patient.