Modulators of toll-like receptor 7

1. A compound represented by Formula Ia:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is —NR 4 R 5 wherein R 4 and R 5 , taken together with the nitrogen to which they are both attached, form a heterocycle selected from the group consisting of:

R 2 is H, alkyl, substituted alkyl, carbocyclyl, substituted carbocyclyl, carbocyclylalkyl, substituted carbocyclylalkyl, arylalkyl, substituted arylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, —C(O)R 6 , —C(O)OR 6 , —C(O)NR 7 R 8 , —S(O) 2 OR 7 , or —S(O) 2 NR 7 R 8 ;

L 3 is —NH—, —O—, —S—, —N(R 9 )C(O)—, —S(O) 2 —, —S(O)—, or a covalent bond;

R 3 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, heteroalkyl, substituted heteroalkyl, carbocyclyl, substituted carbocyclyl, carbocyclylalkyl, substituted carbocyclylalkyl, heterocyclyl, substituted heterocyclyl, heterocyclylalkyl, or substituted heterocyclylalkyl;

R 6 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, heteroalkyl, substituted heteroalkyl, carbocyclyl, substituted carbocyclyl, carbocyclylalkyl, substituted carbocyclylalkyl, heterocyclyl, substituted heterocyclyl, heterocyclylalkyl, or substituted heterocyclylalkyl;

R 7 and R 8 are each independently H, alkyl, substituted alkyl, carbocyclyl, substituted carbocyclyl, carbocyclylalkyl, substituted carbocyclylalkyl, heterocyclyl, substituted heterocyclyl, heterocyclylalkyl, or substituted heterocyclylalkyl; or

R 7 and R 8 , taken together with the nitrogen to which they are both bonded, form a substituted or unsubstituted heterocycle;

R 9 is H, alkyl, substituted alkyl, carbocyclyl, substituted carbocyclyl, carbocyclylalkyl, substituted carbocyclylalkyl, heterocyclyl, substituted heterocyclyl, heterocyclylalkyl, or substituted heterocyclylalkyl, or a prodrug moiety;

R 10 is halogen, cyano, azido, nitro, alkyl, substituted alkyl, hydroxyl, amino, heteroalkyl, or substituted heteroalkyl; and

n is an integer from 0 to 4.

2. The compound of claim 1 , wherein —L 3 —R 3 is —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 , —O-i-butyl, —O-cyclobutyl, —O-cyclopentyl, —OCH 2 -cyclopropyl, —OCH 2 -cyclobutyl, —OCH 2 CH 2 -cyclopropyl, —OCH 2 CH 2 CH 2 CH 2 OH, —OCH 2 CF 3 , —OCH 2 CH 2 CF 3 , —OCH 2 CH 2 CH 2 CF 3 , or (tetrahydrofuran-2-yl)methoxy; and

R 2 is H.

3. The compound of claim 1 , wherein R 1 is NR 4 R 5 and R 4 and R 5 , taken together with the nitrogen to which they are both attached, form a heterocycle selected from the group consisting of:

4. The compound of claim 3 wherein —L 3 —R 3 is —OCH 2 CH 2 CH 2 CH 3 , —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 CF 3 , —OCH 2 CH 2 CH 2 CH 2 OH, or —OCH 2 -cyclopropyl.

5. A compound selected from the group consisting of:

or pharmaceutically acceptable salts, and/or esters thereof

6. The compound of claim 1 or a pharmaceutically acceptable salt, and/or ester thereof, wherein:

—L 3 —R 3 is —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 , —O-i-butyl, —O-cyclobutyl, —O-cyclopentyl, —OCH 2 -cyclopropyl, —OCH 2 -cyclobutyl, —OCH 2 CH 2 -cyclopropyl, —OCH 2 CH 2 CH 2 CH 2 OH, —OCH 2 CF 3 , —OCH 2 CH 2 CF 3 , —OCH 2 CH 2 CH 2 CF 3 , or (tetrahydrofuran-2-yl)methoxy;

R 2 is H;

n 0;

R 1 is —NR 4 R 5 ; and R 4 and R 5 , taken together with the nitrogen to which they are both attached, form a heterocycle selected from the group consisting of:

7. The compound of claim 6 wherein —L 3 —R 3 is —OCH 2 CH 2 CH 2 CH 3 , —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 CF 3 , —OCH 2 CH 2 CH 2 CH 2 OH, or —OCH 2 -cyclopropyl.

8. The compound of claim 7 wherein —L 3 —R 3 is —OCH 2 CH 2 CH 2 CH 3 .

9. The compound of claim 8 wherein R 4 and R 5 , taken together with the nitrogen to which they are both attached form a heterocycle selected from the group consisting of:

10. The compound of claim 1 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising:

at least one compound of claim 1 , or a pharmaceutically acceptable salt, and/or ester thereof; and

a pharmaceutically acceptable carrier or excipient.

12. The pharmaceutical composition of claim 11 , further comprising:

at least one additional active agent.

13. The pharmaceutical composition of claim 12 , wherein:

the at least one additional active agent is selected from the group consisting of interferons, ribavirin, HCV NS3 protease inhibitors, alpha-glucosidase 1 inhibitors, hepatoprotectants, nucleoside or nucleotide inhibitors of HCV NS5B polymerase, non-nucleoside inhibitors of HCV NS5B polymerase, HCV NS5A inhibitors, TLR-7 agonists, cyclophillin inhibitors, HCV IRES inhibitors, pharmacokinetic enhancers, and other drugs for treating HCV, or mixtures thereof.

14. The pharmaceutical composition of claim 13 , wherein the at least

one additional active agent is selected from the group consisting of:

(1) interferons selected from the group consisting of pegylated rIFN-alpha 2b, pegylated rIFN-alpha 2a, rIFN-alpha 2b, rIFN-alpha 2a, interferon alpha, interferon alfacon-1, interferon alpha-n1, interferon alpha-n3, interferon-beta, interferon-omega, albinterferon alpha-2b (Albuferon), IFN alpha-2b XL, BLX-883, DA-3021, glycosylated interferon alpha-2b, PEG-Infergen, PEGylated interferon lambda-1, belerofon, and mixtures thereof;

(2) ribavirin;

(3) HCV NS3 protease inhibitors and;

(4) alpha-glucosidase 1 inhibitors;

(5) hepatoprotectants;

(6) nucleoside or nucleotide inhibitors of HCV NS5B polymerase;

(7) non-nucleoside inhibitors of HCV NS5B polymerase;

(8) IICV NS5A inhibitors;

(9) TLR-7 agonists;

(10) cyclophillin inhibitors;

(11) HCV IRES inhibitors,

(12) pharmacokinetic enhancers; and

(13) other drugs for treating HCV selected from the group consisting of thymosin alpha 1, nitazoxanide, virostat, altirex, actilon®, civacir, tarvacin, Bavituximab, Oglufanide, merimepodib, and mixtures thereof.

15. A combination pharmaceutical agent comprising:

a) a first pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, or ester thereof; and

b) a second pharmaceutical composition comprising at least one additional active agent selected from the group consisting of interferons, ribavirin, HCV NS3 protease inhibitors, alpha-glucosidase 1 inhibitors, hepatoprotectants, nucleoside or nucleotide inhibitors of HCV NS5B polymerase, non-nucleoside inhibitors of HCV NS5B polymerase, HCV NS5A inhibitors, TLR-7 agonists, cyclophillin inhibitors, HCV IRES inhibitors, pharmacokinetic enhancers, and other drugs for treating HCV, or mixtures thereof.