Substituted benzoazepines as toll-like receptor modulators

1. A method of treating ovarian cancer, comprising administering to a subject in need thereof an effective amount of a compound having the formula I:

or a tautomer, enantiomer or salt thereof, wherein:

Y is —(O) x (CH 2 ) y R 11 ;

x is selected from 0 and 1;

y is selected from 0, 1, 2, and 3;

R 11 is selected from aryl, heteroaryl, and saturated or partially saturated heterocycle, wherein when x is 0, said aryl or heteroaryl is substituted with —C(O)NR 1 R 2 or T;

R 1 and R 2 are independently selected from hydrogen and alkyl, wherein said alkyl is optionally substituted with —C(O)O(CH 2 ) t R 12 or R 1 and R 2 together with the nitrogen atom to which they are attached form a saturated heterocyclic ring;

t is selected from 0, 1, 2, and 3;

R 12 is selected from cycloalkyl and aryl;

T is selected from heterocycle, —(CHR 7 ) z OR 9 , —(O) u (CH 2 ) s C(O)R 8 , —OSO 2 R 13 , and —CH(OH)CH 2 OH;

R 7 is H or —OH;

R 8 is selected from —OR 10 and alkyl;

R 9 is selected from alkyl and H;

R 10 is selected from alkyl, —(CH 2 )R 12 , and hydrogen, wherein said alkyl is optionally substituted with halogen, amine, alkylamine, or dialkylamine;

R 13 is selected from —OH, alkyl, CF 3 , cycloalkyl, heterocycle, aryl, and heteroaryl;

u is selected from 0 and 1;

z is selected from 1, 2, and 3;

s is selected from 1 and 2;

R 5 is selected from —NR 3 R 4 and —OR 10 ;

R 3 and R 4 are independently selected from H, alkyl, and —(O) q (CH 2 ) r P; wherein said alkyl is optionally substituted with one or more —OH;

q is selected from 0 and 1;

r is selected from 0, 1, 2, and 3;

P is selected from aryl, —SO 2 R 6 , and heterocycle; and

R 6 is selected from —NH 2 , —NH(alkyl), and —N(alkyl) 2 ,

provided that when R 11 is aryl or heteroaryl, then

a) x+y≧1;

or

b) R 11 is substituted with T;

or

c) R 5 is NR 3 R 4 and at least one of R 3 or R 4 is —(O) q (CH 2 ) r P and q+r≧1;

or

d) at least one of R 1 or R 2 is alkyl substituted with —C(O)O(CH 2 )R 12 .

2. The method according to claim 1 , wherein the compound is of formula II:

or a tautomer, enantiomer or salt thereof wherein:

W is selected from N, C-T and CH.

3. The method according to claim 2 , wherein the compound is of formula IIa:

or a tautomer, enantiomer or salt thereof.

4. The method according to claim 2 , wherein the compound is of formula IIb:

or a tautomer, enantiomer or salt thereof.

5. The method according to claim 1 , wherein the compound is of formula III:

or a tautomer, enantiomer or salt thereof, provided that when R 11 is aryl or heteroaryl, then x+y≧1.

6. The method according to claim 1 , wherein the compound is of formula IV:

or a tautomer, enantiomer or salt thereof, wherein q+r≧1.

7. The method according to claim 1 , wherein the compound is of formula V:

or a tautomer, enantiomer or salt thereof, wherein at least one of R 1 or R 2 is alkyl substituted with —C(O)O(CH 2 )R 12 .

8. The method according to claim 1 , wherein the compound is of formula VI:

or a tautomer, enantiomer or salt thereof, wherein:

R 11 is selected from aryl and saturated or partially saturated heterocycle, wherein said aryl is substituted with T;

T is selected from heterocycle, —(O) u (CH 2 ) s C(O)R 8 , and —CH(OH)CH 2 OH;

R 8 is selected from —OR 10 and alkyl;

R 10 is selected from alkyl, —(CH 2 )R 12 , and hydrogen, wherein said alkyl is optionally substituted with halogen, amine, alkylamine, or dialkylamine;

R 12 is selected from cycloalkyl and aryl;

u is selected from 0 and 1;

s is selected from 1 and 2; and

R 3 and R 4 are independently alkyl; wherein said alkyl is optionally substituted with one or more —OH.

9. The method according to claim 8 , wherein:

R 11 is selected from aryl and saturated or partially saturated heterocycle, wherein said aryl is substituted with T;

T is selected from heterocycle and —(O) u (CH 2 ) s C(O)R 8 ;

R 8 is selected from —OR 10 and alkyl;

R 10 is selected from alkyl, —(CH 2 )R 12 , and hydrogen, wherein said alkyl is optionally substituted with halogen, amine, alkylamine, or dialkylamine;

R 12 is selected from cycloalkyl and aryl;

u is selected from 0 and 1;

s is selected from 1 and 2; and

R 3 and R 4 are independently alkyl; wherein said alkyl is optionally substituted with one or more —OH.

10. The method according to claim 8 , wherein:

R 11 is aryl substituted with T;

T is selected from —(O) u (CH 2 ) s C(O)R 8 , and —CH(OH)CH 2 OH;

R 8 is selected from —OR 10 and alkyl;

R 10 is selected from alkyl, —(CH 2 )R 12 , and hydrogen, wherein said alkyl is optionally substituted with halogen, amine, alkylamine, or dialkylamine;

R 12 is selected from cycloalkyl and aryl;

u is selected from 0 and 1;

s is selected from 1 and 2; and

R 3 and R 4 are independently alkyl; wherein said alkyl is optionally substituted with one or more —OH.

11. A method of treating ovarian cancer, comprising administering to a subject in need thereof an effective amount of a compound selected from the group consisting of:

and tautomers, enantiomers and salts thereof.

12. The method according to claim 11 , wherein the compound is selected from the group consisting of:

and tautomers, enantiomers and salts thereof.

13. The method according to claim 11 , wherein the compound is selected from the group consisting of:

and tautomers, enantiomers and salts thereof.

14. The method according to claim 11 , wherein the compound is selected from the group consisting of:

and tautomers, enantiomers and salts thereof.

15. The method according to claim 1 , wherein the salt is a pharmaceutically acceptable salt.