Modulators of toll-like receptors
Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.
1. A compound having the structure:
or a pharmaceutically acceptable salt thereof, wherein:
L 1 is —NH— or —O—;
R 1 is C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 3 -C 20 heterocyclylalkyl, or C 4 -C 20 carbocyclylalkyl, wherein the heteroalkyl group containing one or more heteroatoms selected from O, N and S, and wherein the heterocyclyl group containing 1 to 4 heteroatoms selected from N, O and S;
each of R 4 and R 5 independently is H or C 1 -C 6 alkyl;
X 1 is C 1 -C 6 alkylene, or C 1 -C 6 heteroalkylene;
D is phenyl, biphenyl or pyridinyl, wherein said phenyl, biphenyl or pyridinyl is substituted with -L 2 -NR 6 R 7 ; or
D is pyridinyl, piperidinyl, piperazinyl or 1,2,3,4-tetrahydroisoquinolinyl;
n is 0 or 1;
R 3 is selected from the group consisting of cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —CHO, or C 4 -C 20 carbocyclylalkyl; and
L 2 is C 1 -C 6 alkylene or a covalent bond;
each of R 6 and R 7 independently is H, or C 1 -C 6 alkyl; or
R 6 and R 7 taken together with the nitrogen to which they are attached form an unsubstituted 4-6 membered heterocycle containing 0 to 2 additional heteroatoms selected from N, O and S.
2. The compound of claim 1 , wherein X 1 is —CH 2 —.
3. The compound of claim 1 , wherein D is phenyl or biphenyl.
4. The compound of claim 1 , wherein D is pyridinyl.
5. The compound of claim 1 , wherein L 2 is —CH 2 —.
6. The compound of claim 1 , wherein L 1 is —O—.
7. The compound of claim 1 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
8. The compound of claim 1 , having the structure:
or a pharmaceutically acceptable salt thereof.